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Digestive system - Coggle Diagram

- - - - MONO-
        
        May be represented by a linear chain of 3 or more carbon atoms.
        --> a carbonyl group - double bond with oxygen
        --> Another carbon contains hydroxyl group
        
        Carbonyl group
        --> is an aldehyde, sugar is an aldose --> Glucose = aldohexose
        --> Ketone = ketose --> EG: Fructose = ketohexose
        
        -ose = sugars
        C3, C4, C5, C6 and C7 =trioses, tetroses, pentoses, hexoses and heptoses.
        
        STRUCTURE
        
        Position of the hydroxyl groups on their asymmetric carbon atoms (C with 4 different types of atoms/groups of atoms)
        
        D- or L-sugars
        --> D and L based on whether the position of the hydroxyl group farthest from the carbonyl carbon.
        
        Enantiomers – stereoisomers that are mirror images of each other.
        Most sugars are often in D series.
        
        RING
        
        Exists in solution
        
        carbonyl group has reacted with a hydroxyl group to form a five/six-membered ring.
        
        Oxygen on the hydroxyl group is now part of the ring.
        
        Original carbonyl carbon, now contains an OH group become the anomeric carbon atom (In a cyclic carbohydrate, the carbon that was the carbonyl carbon in acyclic form.
        
        A hydroxyl group drawn below the ring= α-position, above the ring = β position
        
        In solution, the sugar ring can open and close.
        
        Mutarotation – a type of change in the specific rotation of a solution.
        
        α & β at equilibrium in solution (% as above).
        
        GLYCOSIDE
        
        When the hydroxyl group on the anomeric carbon react with –OH / an –NH group of another compound – glycosides are formed.
        
        The linkage – glycosidic / glycosyl bonds.
        
        It may be either α or β, depending on the position of the atom attached to the anomeric carbon.
        
        N-glycosidic bonds = OH and an amine
        
        O-glycosidic bonds = OH and sugar --> Eg in lactose
        
        SUGAR DERIVATIVES
        
        Contain amino group, phosphate group, sulfate groups, N-acetyl groups.
        
        Galactosamine, glucosamine –amino sugar at C2 and can be acetylated
        
        Free monosaccharides within cells are phosphorylated at their terminal carbons which prevents their transport out of the cell.
        --> Ex: Glucose 6-phosphate
        --> Ex in complex molecules= proteoglycans
        
        Sulfated sugars (with sulphur, oxygen and another element) – heparin (anticoagulant)
        
        chondroitin sulfate (found in joints-building blocks for cartilage-
        
        RIBOSE
        
        a pentose monosaccharide (simple sugar) with linear form H−(C=O)−(CHOH)4−H, which has all the hydroxyl groups on the same side in the Fischer projection.
        
        One of OH is reduced =deoxyribose
        
        Phosphate groups may join sugars to nucleosides (a compound (e.g. adenosine or cytidine) consisting of a purine or pyrimidine base linked to a sugar.
        
        OXIDISED SUGAR
        
        Oxidation at the aldehyde carbon (C1) to form a carboxylic acid.
        --> Name from “-ose” to “-onic acid”/ “-onate”
        --> Ex D-glucose to D-gluconic acid
        
        Oxidation of C6 forms uronic acid --> Ex glucuronic acid
        
        REDUCED SUGAR
        
        Aldehyde group of sugar is reduced, sugar becomes polyalcohol.
        
        carbon atom contain OH=polyol
        
        EXAMPLE:
        Ex: glucose to sorbitol (in sugar-free chewing gums. Laxatives (drug to loosen stools & induce bowel movement) & poorly absorbed by intestines).
        Ex: galactose to galactitol
        
        Activated sugar: UDP-Glucose
        
        Activated sugar nucleotide – activated monosaccharides.
        
        By UTP (uridine triphosphate) - source of energy/activator
        
        UDP-glucose is a precursor OF = glycogen and lactose, UDP-glucuronate carbohydrate chains in proteoglycans, glycoproteins and glycolipids.
        
        SYNTHESIS
        
        A sugar is transferred from the nucleotide sugar to an alcohol to form a glycosidic bond by glycosyltransferases.
        
        High energy bond between UDP & sugar provides energy for formation of a new bond.
        
        Formation of Glucuronides
        
        is any substance produced by linking glucuronic acid to another substance via a glycosidic bond.
        
        to assist in the excretion of toxic substances & drugs.
        
        UDP glucose forms UDP-glucoronates which is the precursor for glucuronides.
        
        By oxidation of the alcohol on carbon 6 of glucose to an acid by an NAD+-dependent dehydrogenase.
      - POLY-
        
        DISACCHARIDE
        
        Disaccharide = 2 monosaccharides joined by an O-glycosidic bond.
        
        Lactose =β-OH anomeric carbon of galactose and the OH on carbon 4 of glucose – β(1🡪4) bond
        
        Maltose
        
        Sucrose
        
        SYNTHESIS
        
        LACTOSE
        
        Synthesized only in the mammary gland of an adult for short period of time during lactation.
        
        Lactose synthase – catalyzes the last step in lactose synthesis.
        
        Has 2 subunits: galactosyltransferase & α-lactalbumin.
        
        POLYSACCHARIDE
        
        Polysaccharides = 10 to 1000 of monosaccharides-linear or branched
        
        Starch – contains amylose (long unbranched chains of glucose units linked α(1🡪4) & branched amylopectin.
        
        Amylopectin and glycogen are branched polymers linked through α(1🡪4) and α(1🡪6) bonds.
        
        Proteoglycans - Long unbranched polysaccharide chain attached to a core protein.
        
        Glycosaminoglycans (GAG) - A long unbranched polysaccharides consisting of a repeating of disaccharides
        E.g - hyaluronic acid are the carbohydrate parts of proteoglycans
        [Highly polar & Facilitates hydration and keeps the proteins unfolded.]
      - OLIGO
        
        Oligosaccharides = 3 to 12 monosaccharides.
        
        Carbohydrate components of glycoproteins & glycolipids.
        
        GLYCOPROTEIN
        
        Covalently linked to either serine/threonine or asparagine residues.
        
        Serve as hormones, antibodies, enzymes, structural components.
        
        Collagen contains galactosyl- glucose attached to hydroxylysine residues
        
        Salivary mucin- secretion of mucus-producing cells
        
        Membrane- cell attachment, cell-cell recognition.--> bacteria and virus binding
        
        Sugar forms hydrogen bonds with water.
        
        Sialic acid provides negatively charged carboxylate group.
        
        BRANCH:
        NANA (N-acetylneuraminic acid) Gal (Galactose) GlcNAc (A acetylglucosamine) Man (Mannose) Fuc (Fucose)
        
        GLYCOLIPID
        
        Derivatives of lipid sphingosine- cerebrosides and gangliosides which contain ceramide with carbohydrate moieties attached to its hydroxymethyl group
        
        CHO residues are the antigens of the ABO blood group substances.
        
        Blood Gp substances are oligos found on most cell membranes (RBC).
        
        Structures are the same except type A has GalNAc (N-acetylgalactosamine) at the nonreducing end.
        
        Type B has Gal.
        
        R either protein or lipid ceramide.
        
        Antigenic determinant
        
        GENETIC
        
        A single genetic locus with two alleles determines an indiv blood type.
        
        These genes encodes for glycosyltransferases involved in the synthesis of the oligosaccharides.
        
        Most indiv can synthesize the H substances.
        
        Type A indiv – produce N-acetylgalactosamine transferase (encoded by the A gene) that attaches N-acetylgalactosamine to the gal residue of H substance.
        
        Type B- produce galactosyltransferase
  - - - MOUTH
        
        Conversion of starch (amylopectin & amylose) to glucose begins in the mouth.
        
        Salivary gland secretes liquid containing mucin & α-amylase)
        
        Mucin – for lubrication & dispersion of polysaccharides.
        
        α-amylase- hydrolyzes α-1,4-bonds converting amylopectin, amylose & glycogen to limit (at the end) dextrin.
      - STOMACH - HCl- denatures α-amylase.
      - DUODENUM
        
        Pancreatic secretions contain HCO3- - neutralizes HCl.
        
        Iα-amylase-hydrolyzes α-1,4-bonds and produces disaccharides (e.g. maltose, isomaltose, oligosaccharides).
      - INTESTINE
        
        Dietary & products of starch digestion (disaccharides & oligosaccharides) are converted to monosaccharides by glycosidases (enzymes that hydrolyzes the glycosidic bonds).
        
        Glycosidases – attached to the membrane in the brush border of absorptive cells.
        
        Present as 4 large complexes protruding from the membrane to the intestinal lumen.
        
        β-glucoamylase, sucrase-isomaltase, lactase ( β-glycosidases), trehalase.
        
        a.k.a small intestinal disaccharidases although glucoamylase is an oligosaccharidase.
      - ENZ
        
        Sucrase-isomaltase complex
        
        Structure is similar to glucoamylase.
        
        Difference: After the single polypeptide chain is inserted through the membrane, an intestinal protease clips it into 2 separate subunits that remain attached to each other.
        
        Each subunit has a catalytic site that differs in substrate specificity.
        
        Glucoamylase
        
        Have a connecting segment and a long polypeptide chain forming 2 globular domain.
        
        Each has its own catalytic site.
        
        Heavily glycosylated to protect from digestive proteases.
        
        Glucoamylase – exoglucosidases specific for α-1,4-bonds.
        
        Begins at the nonreducing end of polysaccharides or limit dextrin and sequentially hydrolyzes the bond to release glucose.
        
        It will digest a limit dextrin down to isomaltose (disaccharide) with α-1,6-bonds.
        
        Then it will be subsequently hydrolysed by isomaltase in sucrase-isomaltase complex.
        
        β-glycosidase complex (Lactase-glucosylceramidase)
        
        Large glycoprotein with 2 catalytic site.
        
        Primary structure is different from others.
        
        Lactase catalytic site hydrolyses β-bond connecting glucose & galactose in lactose.
        
        The other catalytic site is β-bond connecting glucose or galactose and ceramide in glycolipids.
        
        Trehalase
        
        Half in length with only one catalytic site.
        
        Hydrolyses glycosidic bonds in trehalose.
        
        found in insects, algae, mushroom & other dietary fungi.
        
        Not a major dietary component but unwitting (unintentional) consumption can cause severe nausea, vomiting & other severe gastrointestinal distress when the enzyme is deficient in the indiv.
      - DIETARY FIBRE
        
        Is the portion of diet that is resistant to digestion by human digestive enzymes.
        
        It consists principally of plant materials that are polysaccharides derivatives and lignin.
        
        Bacterial flora in normal human gut may metabolizes soluble dietary fibres to gases & short-chain fatty acids. They may also metabolizes undigested starch & sugars.
        
        CATEGORY
        
        Soluble – pectins, mucilages & gums.
        
        Insoluble – cellulose, hemicellulose & lignins.
    - - Once CHO has been split to monosaccharides, the sugars are transported across the intestinal epithelial cells and into the blood for distribution.
        
        Not all CHO sources are digested and absorb at the same rate & time. Some CHO lead to near-immediate rise of glucose levels in blood whereas others slowly raise the glucose level over an extended period of time
        
        The glycaemic index – indicates how rapid blood glucose rise after consumption.
        
        Highest: Glucose & maltose 142 ( with comparison of white bread with an index of 100)
        
        Lowest: yogurt (52) & skim milk (46).
      - BY INSTETINAL EPI.
        
        Na+-dependant facilitated transport
        
        Located on the luminal side to concentrate glucose from the intestinal lumen.
        
        Low intracellular [Na+] is maintained by Na+, K+ ATPase on the serosal side that requires ATP to pump Na+ out of the cell into the blood.
        
        Thus glucose is transported from low conc. in the lumen to high conc in the cell which is promoted by the cotransport of Na+ (from high to low)
        
        The epithelial cells of the kidney have similar transporter.
        
        Na+-dependant and facilitated transport in the intestinal epithelial cells.
        
        Facilitated diffusion-facilitative glucose transporters
        
        Located on the luminal & serosal side of the cells.
        
        Glucose moves from high concentration inside the cell to lower concentration in the blood without the use of energy.
        E.g GLUT1 to GLUT5
      - GALACTOSE & FRUCTOSE
        
        Galactose is absorbed through the same mechanism as glucose.
        
        Fructose both leaves and enters the epithelial cells by facilitated diffusion.
        
        Transport via proteins that are part of the GLUT family.
        
        Luminal side – GLUT5 can transport glucose but with much higher activity with fructose.
        
        Other fructose transport protein may also be present.
        
        For reasons yet unknown, fructose is absorbed more rapidly when ingested as sucrose than when it is ingested as monosaccharides.
      - Stimulation by insulin
        
        In muscle & adipose tissue, transport of glucose is greatly stimulated by insulin.
        
        In adipose tissue, stimulation of glucose transport by insulin increases its availability for the synthesis of fatty acid & glycerol from the glycolytic pathway.
        
        In skeletal muscle, this stimulation increases its availability for glycolysis & glycogen synthesis
  - - - FX: Energy production (ATP).
        
        Provides precursor pyruvate as precursor for fatty acid synthesis.
        
        Provides precursors for synthesis of compounds e.g. amino acids and 5-carbon sugars (pentoses).
        
        2 types : aerobic (with O2) and anaerobic glycolysis.
        
        ANAEROBIC:
        
        Lactic acid fermentation in several types of animal cells and some microorganisms
        
        Ethanol fermentation in yeast and other microorganisms
      - STAGES
        
        Energy investment (first 5 reactions).
        Phosphorylation of glucose and fructose at the expense of ATP.
        
        Energy generation.
        
        A net of 2 ATP is formed per glucose molecule.
        
        2 molecules of NADH are formed when pyruvate is produced whereas NADH is converted to NAD+ when lactate is the end product.
      - ANAEROBIC
        
        Final product – lactate in eukaryotic cells (RBC, lens and cornea of the eye, kidney medulla testes and leukocytes.
        
        Can accumulate in exercising skeletal muscle, intracellular pH↓, potentially causing cramps. Lactate will eventually diffuse into the blood stream to the hepar for glucose synthesis, (Cori cycle).
        
        In liver and heart, lactate will be oxidised to pyruvate.
        
        In liver, pyruvate is either converted back to glucose by gluconeogenesis or oxidised in the Tricarboxylic cycle (TCA) cycle.
        
        The heart muscle will exclusively oxidized lactate to CO2 and H2O via the TCA cycle.
      - Overall energy yield of glycolysis.
        
        Aerobic glycolysis.
        Glucose + 2ATP + 4ADP + 2Pi + 2NAD+ → 2 Pyruvate + 2NADH + 4 ATP + 2H2O.
        
        NET: 2ATP
        
        Anaerobic glycolysis.
        Glucose + 2 Pi + 2ADP → 2 lactate + 2ATP + 2H2O.
      - INHIBITORS
        
        Arsenate (a salt of arsenic acid)
        
        It will compete with inorganic phosphate (Pi) in the seventh reaction:
        
        1,3-Bisphosphoglycerate + ADP → 3-Phosphoglycerate + ATP.
        
        The product is 1-arseno-3-phosphoglyserate which will hydrolyses temporarily plus heat without generating ATP
        
        uncoupler of the oxidation-phosphorylation process
        
        fluoride ions.
        
        The enzyme enolase (step 9) is magnesium dependent.
        
        Flouride ions can form a complex with Mg2+ and phosphate to form a magnesium fluorophosphate complex.
        
        This will inhibit enolase activity and the entire glycolytic sequence will be stopped, no pyruvate will be produced.
        
        Usage : Sodium fluoride is added to blood samples for the glucose test
    - - Also known as Krebs cycle or tricarboxylic acid (TCA) cycle.
        
        Sir Hans Krebs, Nobel prize, 1953.
        
        Place of reaction: Mitochondria
        
        TCA cycle is amphibolic (catabolic and anabolic).
        [Catabolic- metabolic processes that degrades biomolecule.
        Anabolic-metabolic process that build biomolecules]
      - FX
        
        Oxidation of acetyl CoA to CO2 and H2O to produce energy
        
        ATP (GTP).
        -Reducing power of NADH and FADH2
        
        Provides precursors for many biosynthesis pathways
        
        Intermediates of the cycle are starting points for many biosynthetic reactions.
        
        Cycle intermediates can be shared with other pathways.
        
        Reactions feeding into the cycle replenish the pool of cycle intermediates.
      - 8 REACTION
        
        Formation of citrate. - Condensation of acetyl CoA with oxaloacetate
        
        No ATP is needed.
        
        Synthase- inhibited by ATP,NADH, succinyl CoA and acyl CoA.
        
        ACONITASE - Citrate is isomerized to isocitrate
        
        Aconitase contains an ion-sulphur centre as a prosthetic group.
        
        Inhibited by fluoroacetate.
        
        Oxidation and decarboxylation of isocitrate
        
        Release first CO2, produce first NADH of the cycle.
        
        Inhibited by ATP and NADH.
        
        Oxidative decarboxylation of α-ketoglutarate
        
        Release second CO2, produce second NADH of the cycle.
        
        Coenzymes- TPP, FAD, NAD+, lipoic acid and CoA.
        
        Inhibited by ATP, GTP, NADH and succinyl CoA.
        
        Formation of succinate - Also known as succinate thiokinase.
        
        The reaction is coupled to phosphorylation of GDP to GTP.
        
        GTP + ADP ↔ GDP + ATP, nucleoside diphosphate kinase.
        
        Succinyl CoA-precursor for heme biosynthesis.
        
        It can also formed from fatty acids and amino acids.
        
        Oxidation of succinate
        
        Succinate is oxidised to fumarate. FAD is reduced to FADH2.
        
        Malonate- competitively inhibits succinate dh.
        
        Hydration of fumarate - Fumarate is hydrated to malate in a freely reversible reaction catalysed by fumarase.
        
        Oxidation of malate
        
        Malate is oxidised to oxaloacetate by malate dehydrogenase.
        
        Generates the third and final NADH of the cycle
        
        Acetyl CoA + 3NAD+ + FAD + GDP + Pi + 2H2O → 2CO2 + 3NADH + FADH2 + GTP + 3H+ + CoA
    - - Regulation by activation and inhibition of enzyme activity.
        
        By three most important enzyme citrate synthase, isocitrate dehydrogenase anD α-ketoglutarate dehydrogenase complex
        
        Regulation by the availability of ADP.
        
        Effects of low and high ADP.
        
        Rate of oxidative phosphorylation is proportional to the ratio of ADP/ATP.
  - - - Main storage: skeletal muscle, liver and minute amount in many other cells.
        
        Function: fuel reserve for ATP synthesis during muscle contraction & in other cells (emergency source during absence of O2/restricted blood flow).
        
        In general, glycogenolysis & glycolysis are activated together in these cells.
        
        Liver: maintain blood glucose conc. during early stages of fasting.
        
        1st and immediate source of glucose.
        
        In liver, G6P from glycogen is hydrolysed to glu by glu-6-phosphatase (only present in liver & kidney)
        
        Glycogenolysis & gluconeogenesis supplies blood glucose and activated together by glucagon.
        
        Glycogen storage: 10 to 18 hours.
    - - A single molecule of glycogen can have a molecular mass of up to 108 daltons.
        
        Stored in the discrete cytoplasmic granules.
        
        Glycogen is a branched-chain homopolysaccharide made exclusively from α-D-glucose.
        
        Primary glycosidic bond is an α-1,4 linkage. After every eight to ten glucosyl residues, there is a branch containing α-1,6 linkage.
    - - lengthening of the polysaccharide chains of pre-existing glycogen molecule (glycogen primer).
        
        Reducing end is attached to the protein glycogenin
        
        Glycosyl residues are added from UDP-G to the non-reducing ends of the chain by glycogen synthase
      - Formation of glucose 6-phosphate (Glu 6-P) from glucose by hexokinase in most cells and glucokinase in the liver.
        
        Biosynthesis- energy requiring process from uridine triphosphate - UTP (high energy molecule). UDP-Glucose (UDP-G) is synthesised from Glu 1-P.
        
        Glycogen synthesis is catalysed by glycogen synthase and the branching enzyme.
        
        When the chain reaches ~11 residues, a 6-8 residue piece is cleaved by amylo 4,6-transferase (branching enz) & reattached to a glucosyl unit by α-1,6 linkage.
        
        Both chains continue to lengthen until they are enough to produce two new branches.
    - - Glycogen degradation is catalysed by a debrancher enzyme and glycogen phosphorylase.
        
        Glucose 6-phosphatase in the liver generates free glucose from glucose 6-phosphate.
        
        Glycogen phosphorylase starts at nonreducing end.
        
        Cleave glucosyl residues by adding phosphate to anomeric C, releasing Glu-1-P & produce a free 4-hydroxyl gp on the glycogen chain.
        
        One glucosyl residue remaining at α-1,6 branch is hydrolysed by amylo-1,6-glucosidase & free one glucose.
        
        One glucose & ~7-9 glu-1-P residues are released for every branch point.
        
        However, the enzyme cannot act on the glycosidic bonds of 4 glucosyl residues closest to a branch point.
        
        The debrancher enz removes a unit with 3 glu residues & adds it to the end of the longer chain
    - - The regulation of glycogen synthesis in different tissue matches the function of glycogen in the tissue.
        
        In the liver, glycogen serves as the support for blood glucose during fasting or exercising.
        
        Both degradation and biosynthesis pathways are regulated by the insulin/glucagon ratio and by blood glucose level (reflects the availability if dietary glucose).
        
        Degradation of liver glycogen is also activated by epinephrine, which is released in response to exercise, hypoglycemia and other stress condition which demands for blood glucose.
        
        In contrast, in skeletal muscle glycogen acts as the reservoir of the glycosyl units for the generation of ATP from glycolysis and glucose oxidation.
        
        As a result, muscle glycogenolysis is regulated by AMP which signals the lack of ATP and by Ca2+ released during contraction.
        
        Epinephrine, which is released in response to exercise and other stress situation also activates skeletal muscle glycogenolysis
      - LIVER
        
        Glucagon binding to serpentine glucagon receptor or epinephrine binding to β-receptor in the liver activates adenylate cyclase via G protein, synthesize cAMP from ATP.
        
        cAMP binds & activates protein kinase A.
        
        PKA activates phosphorylase kinase by phosphorylation
        
        Phosphorylase kinase adds a phosphate to glycogen phosphorylase b, activating it.
        
        PKA also phosphorylates glycogen synthase, inactivating it.
        
        Because of 4&5, glycogen is degraded to glu-1-P,
        
        Red dashed lines denotes the reactions that decreased in the liver of fasting indiv.
        
        Epinephrine and Calcium
        
        Epinephrine “fight or flight” hormone, released from adrenal medulla in response to neural signals reflecting an increase in demand for glucose.
        
        To flee- muscle needs ATP, needs glucose- therefor liver glycogenolysis must be stimulated.
        
        In the liver, epinephrine stimulates glycogenolysis through 2 types of receptors, the α- and β-agonist receptor.
        
        Epinephrine will act on α-agonist receptor, transmit a signal through G proteins to phospholipase C, which hydrolyzes PIP2 to DAG & IP3.
        
        IP3 stimulates release of Ca2+ from ER.
        
        Ca2+ binds to calmodulin, which activates calmodulin-dependent protein kinase & phosphorylase kinase. Both Ca2+ & DAG activate protein kinase C.
        
        These 3 kinases phosphorylate glycogen synthase at different sites and decrease its activity.
        
        Phosphorylase kinase phosphorylates glycogen phosphorylase b to the active form, activating glycogenolysis & at the same time inhibiting glycogen synthesis.
    - - Initiated by muscle contraction, neural impulses and epinephrine.
        
        AMP produced during degradation of ATP during muscular contraction, will allosterically activates glycogen phosphorylase b.
        
        The neural impulse which initiates contraction will release Ca2+ from the sarcoplasmic reticulum.
        
        Ca2+ will bind to calmodulin, which will activate phosphorylase kinase.
        
        Phosphorylase kinase is also activated through phosphorylation by protein kinase A.
        
        The formation of cAMP and the activation of protein kinase A is initiated by the binding of epinephrine to the receptors.
  - - - Electrons are transferred through a series of enzyme complexes on the fold of inner mitochondrial membrane.
        
        Energy-rich, reduced coenzymes NADH and FADH2, each will donate a pair of electrons to a specialised set of electron carriers described as ETC.
        
        As the electrons are passed down the chain, much of their free energy will be lost.
        
        Part of this energy can be stored by the production of ATP and this process is called oxidative phosphorylation.
        
        Remainder of the free energy not trapped as ATP is released as heat.
        
        Oxygen receives the electrons to form water.
      - ORGANIZATION
        
        Inner mitochondrial membrane can be disrupted to 5 separate enzyme complexes = I, II, III, IV and V
        
        Complex I-IV – part of the chain
        
        Complex V – catalyses ATP synthesis.
        
        Each complex accepts or donates electrons to relative mobile electron carriers such as coenzyme Q and cytochrome C.
        
        Each carrier can receive and donate electrons to the next carrier and ultimately to combine with O2 and protons to form H2O.
      - REACTION
        
        Formation of NADH.
        
        NAD+ is reduced to NADH by dehydrogenase which remove 2 hydrogen atoms from the substrate.
        
        Two e- and one proton (hydride ion (:H) are transferred to NAD+ plus a free H+.
        
        NADH is produced from glycolysis & TCA cycle.
        
        Complex I: NADH:CoQ Oxidoreductase/ NADH DH
        
        Has a binding site for NADH, several FMN (Flavin mononucleotide) & Fe-S centre binding proteins & binding site for CoQ.
        
        An FMN accepts 2 e- from NADH and pass a single e- to Fe-S and then to CoQ.
        
        As e- moves, 4H+ is pumped into the intermembrane space.
        
        Complex II – not a proton pump
        
        Succinate DH, glycerol-3-phosphate DH & ETF-CoQ oxidoreductase also pass e- to CoQ. (ETF-electron transferrin flavoprotein)
        
        ETF-CoQ oxidoreductase accepts e- from ETF.
        
        As CoQ accepts e- and protons from the matrix side, it is converted to CoQH2.
        
        Complex III - Cytochromes.
        
        Each cytochromes ia a protein with a heme group made of a porphyrin ring containing an iron atom
        
        Ferric ions (Fe3+) is reduced to ferrous ion (Fe2+) as they accept the electrons.
        
        Electrons are passed down to the chain to cytochromes b & Fe-S centres (complex III), c1, and c.
        
        Fe2+ is reoxidised to Fe3+.
        
        Cytochromes a + a3 (complex IV).
        
        Electrons are transferred from complex III to complex IV by mobile cytochrome C.
        
        E- is transferred to Copper (CuA), then to cyt a, a3 and CuB.
        
        The transported O2 and free protons are brought together to produced H2O
        
        A whole O2 must accept 4 electrons to be reduced to two H2O
    - - Is the synthesis of ATP by phosphorylation of ADP for which energy is obtained by electron transport and which takes place in the mitochondria during aerobic respiration.
        
        The flow of electrons from NADH to O2 does not directly produce ATP.
      - Chemiosmotic hypothesis
        
        also known as Mitchell hypothesis.
        
        the action of ATP synthase is coupled with that of a proton gradient.
        
        It is the action of the proton gradient that causes a proton motive force that allows ATP synthase to phosphorylate ADP and inorganic phosphate to ATP.
        
        Proton pump – when electrons are transported through the ETC chain, protons are pumped from the matrix to the intermembrane space.
        
        This is done by complex I, III and IV
        
        This process creates an electrical gradient (more positive charges on the outside than the inside of the membrane).
        
        This also create a pH gradient (pH is lower on the outside than the inside of the membrane.
        
        The energy from the proton gradient is sufficient to drive ATP synthesis by complex V- Proton motive force.
      - PROTEIN
        
        Complex V
        (ATP synthase)
        
        Also known as ATPase (because it can also catalyses the hydrolysis of ATP to ADP and Pi
        
        The hypothesis propose that after protons have been transferred to the inner membrane space, they can reenter the matrix by passing through a channel in the ATP synthase molecule, resulting in the synthesis of ATP and at the same time, lowering the electrical and pH gradient
      - TRANSPORT SYS.
        
        ATP-ADP transport
        An adenine nucleotide translocase (ANT), transport ADP from intermembrane space to the matrix and ATP, from the matrix back to the intermembrane space.
        
        Transport of reducing equivalentS
        
        Inner membrane lacks of NADH transporter.
        
        2 electrons of NADH (reducing equivalents) from intermembrane space to the mitochondria using glycerophosphate shuttle.
        
        2 electrons are transferred from NADH to DHAP forming glycerol-3-phosphate(G3P) by cytosolic glycerophosphate DH.
        
        G3P is oxidized to DHAP by mitochondrial glycerophsphate DH.
        
        FAD is reduced to FADH2
        
        Malate-Aspartate Shuttle
        
        NADH produced by glycolysis reduces OAA to malate.
        
        Malate crosses the mitochondria & reoxidises to OAA.
        
        Malate reduces NAD+ to produce NADH that goes to ETC.
        
        OAA transaminated to aspartate & transported out of the cytosol & transaminated to OAA
    - - OXPHOS disease
        
        Gene mutations in either mitochodrial DNA (mtDNA) or nuclear DNA.
        
        The mtDNA encodes for the complex proteins for ETC.
        
        Nuclear DNA encodes for over 70 subunits of proteins involved in the oxidative phosphorylation.
        
        Therefore, ETC will be disrupted, synthesis of ATP is lowered
        
        Examples: Kearns-Sayne syndrom, Pearson syndrom and MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes
      - Brown adipose tissue
  - - - Major source- sucrose, (when cleaved, glucose and fructose will be released).
        
        Other common name for sucrose- sugar cane sugar.
        
        Sucrase - the enzyme in the intestine that will hydrolyze sucrose to glucose and fructose.
        
        Free fructose can be found in many fruits, vegetables, corn syrup and honey.
        
        Entry of fructose into the tissues is not insulin dependent.
    - - Metabolised by conversion to intermediates of glycolysis.
        
        Dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.
        
        Later both will be converted in the liver to glucose, glycogen, pyruvate, lactate or fatty acids.
        
        The rate of fructose metabolism is more rapid than glucose because the trioses formed from frucrose-1-P has bypassed phosphofructokinase-1 (*PFK-1), the major rate limiting step in glycolysis.
      - INTOLERANCE
        
        Fructosuria: Genetic condition with inability to process fructose fruit sugar, leading to its excretion in the urine.
        --> Caused by deficiency in hepatic fructokinase.
        
        Fructosuria: a disorder usually seen in children, the body is unable to metabolize the natural sugar fructose. Attacks of hypoglycemia, marked by seizures, vomiting, and unconsciousness, are treated by giving glucose and eliminating fructose from the diet.
        --> Therapy: rapid detection and removal of fructose and sucrose from the diet.
        
        Also known as Fructose-1-Phosphate Aldolase B Deficiency .
        
        Caused by Aldolase B deficiency.
        
        Clinical symptom appear after dietary ingestion of foods containing fructose or sucrose.
        
        Common symptoms- hepatomegaly, diarrhoea, emesis (action of vomiting), lethargy, failure to thrive, fructosuria and in acute cases, sweating, trembling, coma, seizures and shock due to hypoglycemia.
    - - Major dietary source of galactose –lactose (cleaved lactose will produce galactose and glucose ).
        
        Lactose – found in milk and milk products.
        
        Hydrolysis of lactose is done by intestinal lactase.
        
        Some galactose can also be obtained from lysosomal degradation of complex carbohydrates such as glycoproteins and glycolipids.
        
        Entry to the cells are not insulin dependent.
        
        Metabolised after phosphorylation. ATP is the phosphate donor.
        
        Converted to galactose 1-phosphate by galactokinase found in most tissue.
        
        Galactose-1-phosphate uridyl transferase will transfer uridyl group of UDP-glucose to galactose-1-phosphate to form UDP-galactose.
        
        The enzymes of glycolysis are specific, they do not recognise galactose, therefore UDP-galactose-4-epimerase will convert UDP-galactose to UDP-glucose.
        
        UDP-glucose will go back to the second step, helping the conversion of another galactose-1-phosphate to become UDP-galactose.
        
        Glucose-1-phosphate will be formed and can enter glycogen metabolism by conversion to UDP-glucose by UDP-glucose pyrophosphorylase or;
        
        It can be converted to glucose-6-phosphate by phosphoglucomutase and enter glycolysis
      - DEFICIENCY
        
        Hypergalactosemia and galactosuria– due to galactokinase deficiency.
        
        Hypergalactosemia.
        --> Inborn ability to utilise galactose. Untreated, infant failed to thrive, will become mentally retarded but if eliminate galactose from diet, growth and development will be normal.
        
        Galactosuria --> Heightened levels of galactose in the urine.
    - - Lactose is a disaccharide, consist of a β-galactose attached by a β-1,4-linkages to glucose.
        
        Lactose is also known as “milk sugar” found in milk and other dairy products.
        
        Lactose is produced by the mammary glands found in most but not all mammals.
      - SYNTHESIS
        
        Lactose is synthesised by lactose synthase (UDP-galactose: glucose galactosyltransferase).
        
        The enzyme transfers galactose from UDP-galactose to glucose, releasing UDP.
        
        The enzyme is composed of 2 proteins, A and B.
        
        Protein A- β-D-galactosyltransferase, found in many body tissues. In tissues other than lactating gland, this enzyme transfers galactose from UDP-galactose to N-acetyl-D-glucosamine forming N-acetyllactosamine ( important component in N-linked glycoproteins.
        
        Protein B- only found in lactating mammary glands.
        
        It is called α-lactalbumin and can be found in large quantities in milk.
        
        Protein B will form a complex with protein A, changing the specificity of the transferase, so that lactose will be produced instead of N-acetyllactosamine
        
        HORMONAL CONTROL
        
        Prior to and during pregnancy, the mammary glands synthesises N-acetyllactosamine.
        
        During pregnancy, progesterone hormone will inhibit the synthesis of protein B.
        
        Lactogenesis I (LI) & LII – hormonal control – as long as proper hormones are in place – mom will start making colostrum halfway through the pregnancy & around 30-40 hrs after birth.
        
        Occurs whether or not a mother is breastfeeding the baby.
        
        High levels of progesterone inhibits milk secretion & kept the volume low.
        
        At birth, delivery of placenta results in sudden drop of progesterone/estrogen/human placental lactogen (HPL) level inducing Lactogenesis II (abundant milk production)
        
        But mother don’t typically feel the increase of breast fullness until after 2-3 days after birth.
        
        Importance of colostrum.
        
        FACTORS
        
        Feedback inhibitor of lactation (FIL)- slowing milk synthesis when breast is full (more FIL is present) Speed up when breast is empty (less FIL is present)
        
        Prolactin stimulates the milk synthesis by binding to the prolactin receptor sites on lactocytes (milk-producing cells of the alveoli).
        
        When alveolus is full of milk, shapes of prolactin receptor changes- no binding.
        
        milk synthesis LOW
    - - A polyol is an organic compound containing multiple hydroxyl groups
        
        Named after the first step of sugar alcohol formation from sugars by aldose reductase.
        
        The enzyme is found in many tissues – lens, retina, Schwann cells of peripheral nerves, kidney, placenta, RBCs, cells of ovaries and seminal vesicles.
        
        Function- synthesis of fructose from glucose.
        
        Glucose reduced to sugar alcohol sorbitol. Then oxidized to fructose.
      - In the liver, ovaries, sperm and seminal vesicle cells, there is a second enzyme- sorbitol dehydrogenase, which can oxidise sorbitol to fructose
        
        Spermatozoa utilise fructose as major fuel source while in the seminal fluid, then will switch to glucose once in the female reproductive tract.
        
        Fructose prevents acrosomal breakdown in the plasma membrane of the spermatozoa while still in the seminal fluid.
        
        In the liver, the pathway is to provide mechanism for dietary sorbitol to be converted to s substrate to enter glycolysis or gluconeogenesis.
  - - - Gluconeogenesis – synthesis of new glucose from non-carbohydrate origin.
        
        Brain, red blood cells, kidney medulla, lens and cornea of the eye, testes and exercising muscle require constant supply of glucose.
        
        After prolonged fasting (10 to 18 hours), hepatic glycogen stores will be depleted, therefore glucose will be formed from precursors such as lactate, pyruvate, glycerol (derived from triacylglycerol) and α-ketoacids (derived from amino acid catabolism).
        
        Simply reversing glycolysis will not be possible due to strong favours of pyruvate formation.
        
        7 reactions of glycolysis are reversible and are used in the synthesis of glucose from lactate or pyruvate.
        
        However 3 are irreversible, must be overcome by 4 alternate reactions that favour the synthesis of glucose.
        
        3 IRREVERSIBLE STEPS OF GLYCOLYSIS REPLACED BY 4 STEPS:
        
        pyruvate --> oxaloacetate
        
        OAA --> PEP
        
        F-1,6-BP --> glucose
        
        G-6P --> glucose
      - LOCATION:
        
        90% in the liver
        
        10% in the kidney. After prolonged starvation, kidney will be the major glucose producing organ
      - RXN
        
        Carboxylation of pyruvate.- Carboxylation of pyruvate.
        
        Pyruvate is carboxylated to oxaloacetate (OAA) by pyruvate carboxylase (biotin = cofactor)
        
        Allosterically activated by acetyl CoA (regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site.),
        
        1 ATP hydrolyzed.
        
        Pyruvate carboxylase is found in the liver and kidney cell but not in muscle:
        
        OAA must be transported to the cytosol (where other enzymes of gluconeogenesis are located)
        
        It must be reduced to malate, cross the membrane, reoxidized to OAA back.
        
        Decarboxylation of cytosolic oxaloacetate.
        
        Oxaloacetate is decarboxylated and phosphorylated to phosphoenolpyruvate by phosphoenolpyruvate (PEP) carboxykinase
        
        1 GTP hydrolyzed
        
        Dephosphorylation of fructose 1,6-bisphosphate.
        
        Irreversible hydrolysis of the C-1 phosphate of F-1,6-bis-P by fructose 1,6-bisphosphatase
        
        Dephosphorylation of glucose 6-phosphate
        
        to Glu by glucose-6-phosphatase bypasses the irreversible hexokinase reaction.
        
        Glucose 6-phosphatase can be found in the liver and kidney, not in the muscle.
      - RECIPROCAL REGU. OF GLUCONEO & GLYCOLYSIS
        
        Gluconeogenesis and glycolysis are coordinated so that one pathway is relatively inactive while the other is active
        
        The cellular concentration of fructose 2,6-bisphosphate is set by relative rate of its formation and breakdown.
        Formed by phosphorylation of fructose 6-phosphate catalysed by PFK-2.
        
        Broken down by FBPase-2.
        
        These enzymes are distinct from PFK-1 and FBPase-1. Both are part of a single bifunctional protein.
        
        First control point.
        
        At the reactions catalysed by pyruvate dehydrogenase complex of glycolysis and pyruvate carboxylase of gluconeogenesis.
        
        Pyruvate carboxylase requires Acetyl CoA for its activity.
        
        Biosynthesis of glucose from pyruvate is promoted only when access mitochondrial acetyl CoA builds up beyond the immediate needs of the cell for TCA cycle.
        
        Increased conc. of acetyl CoA will inhibit pyruvate dehydrogenase, stimulating gluconeogenesis by activating pyruvate carboxylase.
        
        Second control point.
        
        Reaction catalysed by fructose 1,6-bisphosphatase, strongly inhibited by AMP.
        
        The corresponding glycolytic enzyme, phosphofructokinase-1 is stimulated by AMP and ADP but inhibited by citrate and ATP.
        
        The two opposing steps in the two pathways are regulated in a coordinated or reciprocal manner.
        
        Third control point
        
        When blood glucose level ↓, glucagon signals the liver to produce and release more glucose. The source: liver and gluconeogenesis.
        
        Hormonal regulation of glycolysis and gluconeogenesis in the liver is mediated by fructose 2,6-bisphosphate.
        
        F-2,6-BP- Allosteric effector for phosphofructokinase-1 (PFK-1)(positive effector) and fructose 1,6-bisphosphatase (FBPase-1)(negative effector).
        
        Fructose 2,6-bisphosphate-activates PFK-1 and stimulate glycolysis. It inhibits FBPase-1, slowing gluconeogenesis.
      - SUMMARY- 2 pyruvate + 4ATP + 2GTP + 2NADH + 2H+ + 6H2O → glucose + 2NAD+ + 4 ADP + 2 GDP + 6Pi + 6H +.
    - - Conversion of lactate to glucose by gluconeogenesis.
        
        Lactate produced from skeletal muscle and other tissues is taken up by the liver and converted to glucose.
        
        The cycling of lactate between muscle and liver is called the Cori cycle.
        
        during exercise, rate of pyruvate prod in miscle is greater than capacity of citric acid cycle to oxidise it --> lactate prod
        
        lactate diffusea into blood, taken up by liver.
        lactate convert back --> glucose in liver through gluconeogenesis
    - - Place of reaction: cell cytoplasm (erythrocytes, liver, adipose tissue and kidney.
        
        FXN:
        ---> Alternative pathway for glucose oxidation.
        --> Generation of NADPH for reductive synthesis of biologically important molecules ( fatty acids, steroids, sorbitol, reduced glutathione)
        --> Production of D-ribose for nucleotide and nucleic acid synthesis.
        -->Important in RBC!
      - PHASE 1: Oxidative reactions (irreversible)
        
        3 reactions, forming ribulose 5-phosphate, CO2 and 2 NADPH for each oxidised Glu-6-P
        
        PHASE 2: Non-oxidative reactions (reversible)
        
        Catalysed the interconversion of 3, 4, 5, 7-carbon sugars.
        
        Permits conversion of ribulose 5-phosphate to ribose 5-phosphate or to intermediates of glycolysis e.g. fructose 6-phosphate and glyceraldehyde 3-phosphate.
        
        Require thiamine pyrophosphate (derivative of thiamine-Vit B1) as coenzyme.
      - Haemolysis caused by reactive oxygen species (ROS)
        
        Maintenance of integrity of RBC depends on the ability to generate ATP & NADPH)
        
        NADPH is used to reduce oxidised glutathione (GSSG) to reduced glutathione (GSH).
        
        GSH is necessary to remove H2O2 & lipid peroxide by ROS
      - Reduction of hydrogen peroxide
        
        Lack of GSH means GSH cannot protect the cell from the reactive oxygen species, which damage the cell membrane by oxidizing the protein and lipid constituents.
        
        As peroxides build up, cell membrane integrity and flexibility is reduced ànd later - haemolysis.
        
        NADPH protects proteins such as haemoglobin from oxidation by protecting the sulphydryl goups in haemoglobins.
        
        Heinz bodies (intracellular haemoglobin precipitates) form from oxidized, denatured haemoglobin (met Hb) which is no longer soluble.
        
        in Met Hb, iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal haemoglobin. Methaemoglobin cannot bind oxygen.
        
        Spontaneously formed methaemoglobin is normally reduced (regenerating normal haemoglobin) by protective enzyme systems, e.g., NADH methemoglobin reductase (cytochrome-b5 reductase) (major pathway), NADPH methaemoglobin reductase (minor pathway. Disruptions with these enzyme systems lead to methaemoglobinemia.
    - - Glukosa 6-Phosphate dehidrogenase (G6PD) deficiency.
        
        Inherited disease
        
        X-linked enzyme deficiency.
        
        Caused by mutation at the genes coding for G6PD.
        
        In erythrocytes, diminished G6PD activity, impairs the ability to form NADPH, resulting in haemolysis.
        
        NADPH is needed to detoxify free radicals and peroxides formed inside the cell.
        
        Most individuals who have inherited one of the G6PD mutations do not show clinical manifestations.
        
        However, some patients with G6PD will develop haemolytic anaemia if =
        --> Treated with ‘oxidant drugs’- anti malarial drugs.
        --> Ingestion of fava beans (kacang parang) or broad beans.
        --> Infection.
        --> Neonatal jaundice
- - - - Bulk storage of food.
        
        Mechanical & chemical breakdown of food.
        
        Secretion of gastric juice (HCl & Pepsin begins protein digestion )
    - - Receptive relaxation
        
        triggered by movement of pharynx & esophagus
        
        to accommodate large volume of food with little change in pressure (vagovagal reflex initiated by distension of the stomach)
        
        Orad region relaxes to accommodate the ingested meal
        
        CCK participates in receptive relaxation by increasing the distensibility of the orad stomach
      - Mixing and digestion
        
        The caudad region contracts to mix the food with gastric secretion and begins the process of digestion.
        
        The size of food particles is reduced.
      - Gastric slow wave (BER) - coordinate peristalsis in stomach
        
        Slow wave potentials (3 waves/min). It depolarizes the smooth muscle cells.
        
        If threshold is reached during the slow waves, action potentials are fired, followed by contraction.
      - Peristaltic contraction
        
        to mix the food
        
        to control gastric emptying
        
        A wave of contraction closes the distal antrum. Thus, as the caudad stomach contracts, food is propelled back into the stomach to be mixed (retropulsion).
        
        Increased by vagal stimulation and decreased by sympathetic.
      - GASTRIC EMPTYING
        
        CHO - increase the rate of emptying
        
        Prot - gastric emptying is slower
        
        Fat - slowest
        
        Hypo/hyperosmolality of duodenal contents - decrease gastric emptying
        
        H+ in duodenum - decrease gastric motility
        
        GASTRIC MUCOSA
        
        Oxyntic gland area (80%):
        
        includes the body & fundus
        
        secretes mucus (mucus neck cells)
        
        secretes HCl, intrinsic fc (parietal cells)
        
        secretes pepsinogen (chief cells)
        
        Pyloric gland area (20%):
        
        antrum
        
        synthesizes & releases gastrin (G cells)
        
        secretes mucus
    - - Mucus
        
        Mucous cells secrete large quantities of viscid mucus that coats the stomach mucosa with a gel layer of mucus
        
        Characteristic of this mucus is that it is alkaline
        
        Tight junction between epithelia cells forming mucosal barrier
        
        FXN
        
        Lubrication
        
        Protection from injury and self-digestion by forming a gastric mucosal barrier.
      - HCl
        
        Activates pepsinogen
        
        Breakdown connective tissues & protein fibres
        
        Denatures protein molecules
        
        Kills microorganisms
        
        Helps in ferric reduction
      - Intrinsic factor
        
        A glycoprotein
        
        Secreted by parietal cells
        
        Combines with B12 (cyanocobalamin) in stomach
        
        B12 is absorbed in terminal ileum
      - MECHANISM
        
        Parietal cells secrete HCl into the lumen of the stomach and, concurrently, absorb HCO3- into the blood stream as follows:
        
        In the parietal cells, CO2 and H2O are converted to H+ and HCO3- , catalyzed by carbonic anhydrase. H+ comes from H2CO3
        
        H+-K+ ATPase in apical membrane of parietal cells pumps H+ against concentration gradient in exchange for K+. Cl – is secreted along with H+, thus the secretion product of the parietal cells is HCl.
        
        Cl- extruded down electrochemical gradient in exchange for HCO3-. The HCO3- is absorbed into the venous blood, the pH of blood increases (alkaline tide). Eventually, this HCO3- will be secreted in pancreatic secretion to neutralize H+ in the small intestine.
        
        STIMULATION
        
        Nerve stimulation (vagus & ENS) – through Ach
        
        acid in stomach – through enteric nerve reflex
        
        Gastrin
        
        Histamine
        
        Normally, present in small amount.
        
        Cofactor for acid secretion --> multiplicative effect of ACh, gastrin & histamine.
        
        Histamine rec on parietal cells: H2 rec.
        
        VAGAL
        
        In the direct pathway, the vagus nerve innervates parietal cells and stimulates H+ secretion directly. Neurotransmitter ACh synapses with muscarinic (M3) receptor on the parietal cells.
        
        In the indirect pathway, the vagus nerve innervates G cells and stimulates gastrin secretion, which stimulates H+ secretion. Neurotransmitter is gastrin releasing peptipe (GRP).
        
        Atropine, a cholinergic muscarinic antagonist, inhibits H+ secretion by blocking ACh.
        
        GASTRIN
        
        Is released in response to eating a meal (small peptides, distension of stomach, vagal stimulation)
        
        Stimulates H+ secretion by interacting with cholecystokinin (CCK) receptor on parietal cells
    - - GASTRECTOMY
        
        DISEASE
        
        Iron deficiency anemia – less gastric acid production, acid is necessary to convert dietary iron to a form that is more readily absorbed in the duodenum)
        
        Pernicious anemia - intrinsic fc deficiency (less absorption B12 vitamin in ileum – less production of healthy erythrocytes)
        
        Dumping syndrome (rapid gastric emptying)
        
        Hypoglycemic symptoms - rapid absorption of glucose (weakness, dizziness, hunger etc)
        
        Hypovolemia & hypotension - rapid entry of hypertonic meals into intestine
  - - - Divided into 3 segments: duodenum, jejunum & ileum
        
        Functions: final digestion of food (pancreatic juice) & absorption of nutrient, water, vitamins & minerals
    - - FOLLOWING MEAL
        
        Peristalsis --> to propel chyme along GIT
        
        Segmentation --> to mix & fragment the chyme
      - BTW MEAL/FAST
        
        Migrating motor complex
        
        uneven contraction to sweep undigested content,
        
        to maintain low bacterial count in upper SI
      - CONTROL
        
        Myogenic - slow waves & spike potentials
        
        Intrinsic neurons - e.g. peristaltic rflx
        
        Extrinsic neurons - e.g. intestino-intestinal rflx
        
        CNS - e.g. emotion
        
        Chemicals --> serotonin, gastrin, motilin ( stimulate contraction)
        --> Adr, secretin - inhibit contraction
    - - Mucus + HCO3- --> Brunner’s glands (duodenal glands) & goblet
        
        cells protection, lubrication, binds bacteria
        
        HCO3- neutralizes the acidic chyme that reaches the duodenum
        
        Surfaces / brush border of enterocytes contain enzymes to finish digestion of CHO & peptides --> disaccharidase, aminopeptidase
        Isotonic fluid (cript of Lieberkühn) to help in absorption
      - REGULATION
        
        Local stimuli - presence of chyme
        --> enteric nerves
        --> tactile / irritant stimuli
        
        Hormones --> secretin, cholecystokinin (CCK)
    - - MAJOR
        
        CARBO - Starch (amylopectin, amylose), glycogen, sucrose, lactose, fructose & glucose
        
        Digestion begins in the mouth by salivary amylase (pH~7):
        Starch --(α-amylase) --> oligosaccharides
        
        α-amylase is denatured by gastric acid.
        
        In small intestine CHO is digested by pancreatic amylase.
        
        Oligosaccharides are further digested by brush border oligosaccharidases (isomaltase, maltase) & disaccharidases (sucrase, lactase).
        
        Deficiency of oligosaccharidase leads to diarrhea, bloating and flatulence (e.g. lactase deficiency – undigested lactose creates an osmotic gradient that draws H2O into the intestinal lumen, bacteria in large intestine attacks lactose as energy source – producing CO2 and methane ).
        
        Only monosaccharides are absorbed.
        
        α-amylase (salivary & pancreatic) hydrolyze 1,4-glycosidic bonds in starch, yielding maltose, maltotriose, and α-limit dextrin.
        
        Maltase, α-dextrinase and sucrase in the intestinal brush border then hydrolyze the oligosaccharides into glucose.
        
        Lactase degrades lactose to glucose and galactose
        
        Trehalase degrades trehalose to glucose
        
        Sucrase degrades sucrose to glucose and fructose
        
        ABSORPTION OF MONOSACCHARIDE
        
        Secondary active transport – depends on intraluminal Na+ amount.
        
        Glucose (& galactose) from the lumen, use sodium-dependent glucose transporter (SGLT).
        
        Glucose is transported by GLUT2 into the interstitium.
        
        Facilitated diffusion – non-sodium dependent
        
        Intraluminal fructose is absorbed by (GLUT5), and into the interstitium via GLUT2.
        
        Some fructose are converted to glucose in the mucosal cells.
        
        PROTEIN - About 50% from diet; 25% from digestive juice; 25% from desquamated mucosal cells
        
        Protein digestion begins in the stomach by pepsin (pH~1.6-3.2).
        
        Polypeptides are further digested by pancreatic proteolytic enzymes & brush border peptidase (aminopeptidases, carboxypeptidases, endopeptidases & dipeptidases).
        
        Some dipeptides & tripeptides are actively transported into enterocytes and hydrolysed by intracellular peptidases.
        
        --> Endopeptidases
        
        degrade proteins by hydrolyzing interior peptide bonds
        --> Exopeptidases
        
        hydrolyze one amino acid at a time from the C terminus of proteins and peptides
        --> Pepsin is not essential for protein digestion
        
        Is secreted as pepsinogen by chief cells of the stomach
        
        Pepsinogen is activated to pepsin by gastric H+ (optimum pH 1-3)
        
        Pepsin is denatured at pH>5, in the intestine with the presence of HCO3- in pancreatic fluid
        
        PANCREATIC PROTEASES
        
        Trypsinogen is activated to trypsin by a brush border enzyme, enterokinase
        
        Trypsin converts chymotrypsinogen, proelastase, procarboxypeptidase A and B to their active forms. Even trypsinogen is converted to more trypsin by trypsin.
        
        After digestion completed, the pancreatic proteases degrade each other and absorbed along with dietary proteins.
        
        ABSORP' OF AA
        
        absorbed in the form of amino acid, dipeptides and tripeptides
        
        mainly as free amino acids
        --> cotransport with Na+ in the luminal membrane;
        --> independent of Na+ (a.a. from cell to blood by facilitated diffusion)
        
        di- and tripeptides
        
        cotransported with H+ in the luminal membrane;
        
        Cytoplasmic peptidases hydrolyze dipeptides & tripeptides to amino acids in the intestinal cells
        
        a.a. from cell to blood by facilitated diffusion
        
        Larger peptides – transcytosis
        
        infants absorb maternal Ab in breast milk
        
        significant factor in the development of food allergies / food intolerances
        
        LIPID - Most dietary fats are in the form of neutral fats i.e. triglycerides
    - - ELECTROLYTES
        
        Most of absorbed ions & water come from GI secretion
        
        Important ions: Na+, K+,Ca+, Cl-, HCO3-, Fe2+
        
        Excessive loss of intestinal secretion (thru diarrhea) are lethal
        
        Most absorption occurs in duodenum & jejunum
        
        Bile salts absorption: terminal ileum
        
        Basolateral Na+-K+ pump maintain low intracellular Na+ & negative membrane potential
        
        Na+ & Cl-
        
        proximal small intestine
        
        Co-transport with glucose, a.a.
        
        Counter-transport - in exchange with H+
        
        Passive diffusion- down its electrochemical gradients
        
        ILEUM
        
        Na+ absorption is coupled with Cl-
        
        distal ileum, Cl- is exchanged with HCO
        
        Ca+
        
        Regulation: negative feedback thru parathyroid hormone
        
        Ca2+ and Mg2+ absorption is facilitated by protein.
        
        Ca2+ is inhibited by phosphates and oxalates – form insoluble salts with Ca2+
        
        Across basolateral memb: against electrochem gradient
        --> Ca2+-ATPase & Na+-Ca2+ exchanger
        
        FROM LUMEN
        
        proximal small intestine (duodenum)
        
        against electrochem gradient (thru Ca2+-binding prot)
        
        initiated by 1,25-(OH)2-D3 (1,25-dihydroxycholecalciferol) active form of vit D3 (cholecalciferol)
        
        Fe
        
        Absorbed from all parts of small intestine, more prominent in duodenum & jejunum
        
        in form of heme or inorganic iron
        
        transported by transferrin gastric acid & organic acid (ascorbic, citric acids) help in dietary iron absorption --> form soluble complexes
        
        Fe3+ is reduced to Fe2+ by ferric reductase and absorbed via iron transporter on brush border.
        
        Phytic acid (cereal), phosphates & oxalates form insoluble compounds with iron and inhibit iron absorption.
        
        VITAMIN
        
        H2O SOL.
        
        B1, B2, niacin, C, folic acid, B6, B12, pantothenic acid, biotin
        
        mostly thru passive diffusion specific transport (Na+-dependent) - B1, folic acid, C (+ passive)
        
        intrinsic fc-B12 cmplx binds to receptor at terminal ileum
        
        FAT SOL. - (A, D, E, K) are absorbed together with fats
      - WATER
        
        In response to osmotic forces
        
        Dependent on absorption of solutes
        --> dissolved substances are absorbed --> LOW osmotic pressure --> water diffuse thru intestinal membrane / tight junction into cytoplasm / paracellular spaces
  - - - Secretion of pancreatic juice is primarily under neural and hormonal control. The stimuli that trigger pancreatic juice secretion are:
        
        acetylcholine released from parasympathetic nerve endings.
        
        the presence of an acidic chyme in the duodenum releases secretin.
        
        the presence of chyme containing fatty acids and amino acids in the duodenum increases CCK release.
      - These stimuli produce different regulatory feedback actions to stimulate pancreatic juice secretion:
        
        Autonomic parasympathetic nerves delivered via the vagus nerve, and CCK cause mainly secretion of large quantities of digestive enzymes by the acinar cells.
        
        Secretin causes the pancreas to secrete large quantities of fluid with high concentration of bicarbonate ions.
      - MODIFI
        
        Acinar cells – produce a small volume of initial pancreatic secretion, mainly Na+ and Cl-
        
        Ductal cells
        
        modify the initial pancreatic secretion by secreting HCO3- and absorbing Cl- via a Cl- -HCO3- exchange mechanism in the luminal membrane
        
        Pancreatic ducts are permeable to H2O, water moves into the lumen to make the pancreatic secretion isosmotic
    - - Pancreatic amylase which catalyzes the hydrolysis of starch, glycogens and most carbohydrates (except cellulose) to form oligosaccharides (mixture of di- and trisaccharides and also dextrin) in the duodenum.
        
        Pancreatic lipase is the main enzyme for fat digestion. It hydrolyses neutral fats to fatty acids and monoglycerides.
        
        Cholesterol esterase which hydrolyses cholesterol esters, and phospholipase which splits phospholipids to fatty acids.
        
        Bile, produced by the liver and stored in/released from the gall bladder, emulsifies fats to increase their surface area for subsequent chemical digestion by pancreatic lipases.
    - - Bicarbonate produced from CO2 and H2O is secreted by an apical Cl--HCO3- antiport in the presence of CA.
        
        Chloride from ECF enters the ductal cells via the basolateral cotransporter with sodium and potassium and leaves via apical channel.
        
        The rate of bicarbonate secretion depends on the availability of luminal Cl-, which is dependent on the Cl- channel (CFTR) in the apical membrane. So, in an absence of ECF Cl-, bicarbonate secretion is decreased significantly.
        
        The H+ formed by dissociation of carbonic acid inside the cell are reabsorbed into the circulation in exchange for Na+ using Na+-H+ antiport.
      - Composition of pancreatic secretion:
        
        High volume
        
        Virtually the same Na+ and K+ conc. as plasma
        
        Much high HCO3- conc. than plasma
        
        Much lower Cl- conc. than plasma
        
        Isotonicity
        
        Pancreatic lipase, amylase & proteases
        
        At low flow rates,
        --> The pancreas secretes an isotonic fluid composed mainly of Na+ and Cl-
        
        At high flow rates,
        -->The pancreas secretes an isotonic fluid composed mainly of Na+ and HCO3-
        --> Little time for exchanged HCO3- for Cl- (high HCO3- conc.)
    - - CF
        
        CYSTIC FIBROSIS = Disorder of pancreatic secretion
        
        Results from a defect in Cl- channels that is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
        
        Associated with a deficiency of pancreatic enzymes resulting in malabsorption & steatorrhea
        
        In CF, impaired anion transport into the proximal ducts results in decreased secretion of more acidic fluid, which leads to precipitation of secreted proteins.
        
        Intraluminal obstruction of the ducts then causes progressive pancreatic damage and atrophy.
  - - - Cecum, colon (ascending,, transverse, descending, sigmoid), rectum, anus
    - - Absorption of Na+, Cl- & H2O
        
        Secretion of HCO3-
        
        Store & concentrate fecal matter
        
        Bacteria can digest some indigestible CHO
        
        By products of colonic bacterial metabolism:
        --> forms of vit K, B12, thiamin, riboflavin (significantly absorbed)
        --> gases – contribute to flatus (e.g. CO2, H2S & methane)
        --> bile pigment – brown colour of the stool
    - - Na+ - active & enhanced by aldosterone
        
        Cl- = electrical gradient, in exchange with HCO3-
        
        H2O = osmotic gradient
        
        Drugs = Anesthetics, sedatives, tranquililzers, steroids.
    - - Net secretion of K+ & HCO3-
        
        HCO3- to neutralize acidic end products of bacterial action
        
        Mucus provides lubrication
    - - Haustration --> slow & non-propulsive mixing movement for absorption
        
        Mass movement --> massive & sustained contraction to propel colonic contents to rectum
    - - Initiated by movement of feces into rectum
        
        Distension of rectum stimulates stretch rec in the rectal wall.
        
        Signals sent to increase peristaltic waves in the rectum & the rest of the colon.
        
        At the same time reflex relaxation of internal anal sphincter occurs which produces the urge to defecate.
        
        External anal sphincter can be controlled voluntarily.
        
        Defaecation occurs when the external anal sphincter relaxes.
        
        Increased intraabdominal pressure (valsalva manoeuvre & contraction of abdominal muscles) with relaxation of external anal sphincter result in defaecation.
        
        Normal bowel frequency ranges from 3x/day to once every third day.
        
        Diarrhoea – urgency of defaecation / faecal incontinence / increased stool freq & loose / watery stools.
        
        Constipation – infrequent passage of hard stools (straining, sensation of incomplete evacuation, perianal / abdominal discomfort)
    - - DIARRHEA
        
        Maximum absorption capacity of large intestine - 5 to 7 L of fluid & electrolytes per day
        
        If total quantity of fluid entering large intestine exceeds its max absorption – diarrhea.
        
        CAUSE
        
        enteritis – inflammation cause irritation, increased secretion
        
        cholera – cholera toxin stimulates excessive electrolytes and fluid secretion (Na+ & H2O follow Cl- into the lumen - secretory diarrhea)
        
        psychogenic diarrhea – excessive stimulation of parasym nerves increases both motility and mucus secretion
      - CONSTIPATION
        
        Slow movement of feces thru large intestine
        
        Excessive amount of fluid absorbed - feces become hard & dry
        
        CAUSE- irregular bowel habits; inadequate dietary fibers, fluids & lack of exercise; tumors; ulcers etc
  - - - META ACT
        
        Glycogen synthesis & breakdown, Gluconeogenesis (conversion of non-CHO to glucose), Urea production, Amino acids & prot. synthesis, Fat metabolism, Lipoprot. & cholesterol systhesis
      - Bile synthesis & secretion
        
        Plasma protein synthesis – albumin, carrier prot, clotting factors
        
        Formation of 25-hydroxycholecalciferol from vit D
        
        Detoxification of drugs, hormones & toxic products
        
        Phagocytosis – removal of aging blood cells and bact by Küppfer cells
        
        Vit & mineral store – Fe, Cu, vitamins
    - - Synthesis in the liver and stored in the gallbladder.
        
        Bile salts are recycled via the enterohepatic circulation.
        
        95% of the bile salts are absorbed in the small intestine mainly in the terminal ileum through Na+-cotranspoters.
      - COMP
        
        Bile salts & acids
        
        Bile pigments – bilirubin from RBC breakdown
        
        Lecithin
        
        Cholesterol
      - ACT' BILE SALT
        
        They emulsify fat to aid in digestion.
        They form micelles to keep lipids in solution and carry them to brush border to be absorbed.
        
        LIPID ABSORTION
        
        Micelles bring the products of lipid digestion (fatty acids, monoglycerides & cholesterol) into the contact with the absorptive surface of the intestinal cells.
        
        In the intestinal cells, the lipid products are re-esterified to triglycerides, cholesterol ester & phospholipids and with apoproteins, form chlylomicrons.
        
        Chylomicrons are transported out of the intestinal cells by exocytosis. Because chylomicrons are too large to enter the capillaries, they are transferred to lymph vessels and added to the bloodstream via thoracic duct.
    - - Steatorrhea- occurs due to impaired digestion and absorption of fat.
        
        FACTOR
        
        Lipase deficiency (e.g. pancreatitis, cystic fibrosis)
        
        Low pH in the intestinal contents
        --> Hypersecretion of gastric acid: gastric H+ secretion is increased, duodenal pH is decreased. Low duodenal pH inactivates pancreatic lipase
        --> Lack of alkaline secretion
        
        Defective reabsorption of bile salts in the terminal ileum (depletion of bile acid pool, bile acids do not recirculate to the liver)
- - - - Enzymatic catalysis - Enzymes, hormones – regulation
        
        Movement- Muscle proteins – actin and myosin
        
        Structural support - Bone – Collagen – framework for deposition of calcium phosphate crystals.
        
        Binding, transport & storage of blood – hemoglobin, albumin
        
        Immune protection- antibodies
        
        Generation and transmission of pulse – NT
        
        Regulation of cell function – hormones and growth factors.
      - BUILDING BLOCK
        
        Amino acids – polymers
        
        20 amino acids – mammalian PROTEIN
        
        All are α-amino acids except proline.
        [The carbon atom next to the carboxyl group CALLED A-carbon]
        
        Amino acids containing an amino group bonded directly to the alpha carbon = alpha amino acids.
    - - PRIMARY
        
        Many genetic diseases – proteins with abnormal amino acid sequences.
        
        The 6th aa glutamic acid is substituted by valine causing the Hb to collapsed.
        
        PAPER ELECTROPHORESIS- Know primary structure of normal and mutated proteins- information used for diagnosis.
        
        STRUCTURE
        
        R (side chain)
        
        Different for each of the 20 amino acids.
        
        can make them behave as weak acid, weak base, hydrophile (polar) & hydrophobe (nonpolar).
        
        α-carbon is asymmetry (because of 4 diff gps). amino acid may exist in either D or L form.
        
        L-configuration occurs in human body.
        
        D-amino acids are found in bacterial cell walls & some antibiotics.
        
        Chiral (hand)- mirror image & nonsuperimposable
        
        CLASSIFICATION
        
        Based on relative polarity of side chains (R).
        
        Indicates their tendency to react.
        
        Range from very nonpolar to very polar.
        
        Some amino acids have very hydrophobic (nonpolar) side chains.
        
        Others more hydrophilic with polar but uncharged R groups.
        
        Most hydrophilic amino acids have side chains with either negative or positive charge at pH 7
        
        TYPE
        
        Nonpolar-aliphatic
        
        (carbon and hydrogen joined together in straight chains, branched trains or non-aromatic rings., aromatic (flat ,ringed-shaped) & branched side chain.
        
        Polar, uncharged
        
        Polar, charged (negative-acidic, positive-basic).
      - SECONDARY
        
        Polypeptide backbone does not assume or form random 3-Dimentional structure.
        
        Forms regular arrangements of amino acids that are near to each other.
        
        ARRANGEMENT
        
        α-helix
        
        Most common
        
        Spiral structure with tightly packed coiled polypeptide backbone with side chains extend outward.
        
        Diverse group of proteins – keratins (near entirely α-helix).
        
        hemoglobin – 80% α-helix, globular (flexible).
        
        HYDROGEN BOND
        
        Each oxygen or carbonyl group forms a hydrogen bonds with hydrogen atom attached to nitrogen of the 4th amino acids further along the chain.
        
        Ensures all except 1st and last peptide bond are linked to each other.
        
        These bonds are weak individually but collectively stabilize the helix structure
        
        Amino acid per turn
        
        Each turn contains 3.6aa, spaced 3 or 4 apart in 1o sequence.
        
        Amino acids that disrupts helix
        
        Proline – forms a ring structure
        
        bulky side chains – tryptophan or amino acids that branched at β-carbon – valine and isoleucine.
        
        Large number of charged aa (glu, asp,his,lysine or arg), forms ionic bonds or repelling with each other.
        
        β-sheet
        
        Another form of secondary structure.
        
        Involves hydrogen bonding.
        
        Surfaces appear ‘pleated’ – often called β-pleated sheets.
        
        Can be illustrated as broad arrows.
        
        Composed of ≥ 2 peptide chains (β - strands).
        
        Hydrogen bonds are perpendicular to polypeptide backbone.
        
        ARRANGEMENT
        
        β-sheet can be arranged either parallel (all N-terminus together) or antiparallel (C-terminal and N terminal alternating) to each other.
        
        Interchain bonds – hydrogen bond formed between polypeptide backbones of separate polypeptide.
        
        β-sheet can also be formed by a single polypeptide chain folding back on itself.
        
        Hydrogen bonds are intrachain bonds.
        
        Example amyloid proteins – deposited in brains of indiv. with Alzheimer’s disease.
        
        β- bends/turns
        
        Reverse direction of polypeptide chain to form a compact and globular shape.
        
        Often found on surface of protein molecules.
        
        Connect successive strands of antiparallel β- sheets.
        
        β- bends are generally composed of 4 amino acids with one proline & glycine.
        
        β-bends are stabilized by formation of hydrogen & ionic bonds.
        
        Supersecondary structures (motifs)
        
        Globular proteins are constructed by combination of α-helices, β-sheets, & non-repetitive sequences. – these forms the core region.
        
        Connected by loop regions (β-bends) at surface of the proteins.
        
        AMYLOID
        
        Amyloid is a general term for protein fragments that the body produces normally.
        
        Beta amyloid is a protein fragment snipped from an amyloid precursor protein (APP).
        
        In a healthy brain, these protein fragments are broken down and eliminated.
        
        In Alzheimer's disease, the fragments accumulate to form hard, insoluble plaques.
      - TERTIARY
        
        Primary structure determines its tertiary structure.
        
        The shape of a 3-D conformation of a globular protein involves interactions between amino acid residues that may be located far from each other.
        
        Globular proteins in aqueous solution is compact with high density atoms in the core of the molecules.
        
        Hydrophobic side chains buried in the interior, while hydrophilic groups on the surface.
        
        stabilize the tertiary structure.
        
        Electrostatic interactions- Interaction between & among cations and anions.
        
        Hydrogen bonds - A chemical bond in which a hydrogen atom of one molecule is attracted to an electronegative atom, especially a nitrogen, oxygen, or fluorine atom
        
        Hydrophobic interaction -hydrophobic amino acids (such as alanine, valine, leucine, isoleucine, phenylalanine, tryptophan and methionine) clustered together within the protein.
        
        DOMAIN
        
        fundamental functional & 3-D structural units of polypeptide (with specific function i.e binding site of small molecule.
        
        Generally polypeptide with ≥ 200 amino acids will have ≥2 domains.
        
        Core domain is built from supersecondary structure (motifs).
        
        Folding of peptide chain within domain usually occurs independently of folding in other domains.
        
        Proteins can be denatured with organic molecules e.g urea (disrupts hydrogen bonding patterns) & β-mercaptoethanol (disulphide bonds) or by heating.
        
        Under certain conditions, denatured proteins can refold into their native conformation, regaining original function.
        
        Many simple single-subunit proteins such as nucleases that are denatured, can refold spontaneously into native conformation if they are brought back carefully.
        
        In the cell, not all proteins can fold back into their native conformation.
        
        As proteins fold & refold while searching for its lowest energy state, it passes thro many high-energy conformations that slow the process (kinetic barriers).
        
        These kinetic barriers can be overcome by heat-shock proteins, which use energy provided by ATP hydrolysis to assist in the folding.
        
        HSP
        
        their synthesis in bacteria is increased when temperature increased suddenly.
        
        In human cells – different families of proteins with different activities.
        
        HSP70 bind to nascent (recently formed) polypeptide chain as their synthesis is being completed to prevent the incomplete chains from folding prematurely.
        
        The multisubunit barrel-shaped hsp60 family of proteins is called chaperonins.
        
        Unfolded protein fits into the barrels cavity that excludes water and serves as templates for folding process.
        
        ATP is hydrolysed to overcome the energy barriers to reach the native conformation.
        
        CHAPERONINS
        
        a group of proteins that are required for proper folding of many proteins.
        
        Also known as polypeptide chain binding (PCBs) – acts as catalysts by increasing the rate of folding at the final stages of folding process.
      - QUARTENARY
        
        3D structure of a protein composed of multiple subunits.
        
        Theses subunits are held together by the same non-covalent interactions (hydrophobic interactions, hydrogen bonds, ionic bonds) involved in tertiary structure.
        
        4 polypeptides, 2 α-chains, 2 β-chains, 4 heme groups, 4 subunits held together by non-covalent interactions, tetramer with 2 identical dimers, Dimers (αβ)1 and (αβ)2 & 2 polypeptide within the dimer is held by hydrophobic interactions
    - - Ion-exchange
      - Gel filtration
      - Affinity
      - SDS Gel electrophoresis
        
        Isoelectric focusing
        
        Antibody technique
        
        Posttranslational modification (PTM)
        
        PHOSPHORYLATION
        
        GLYCOSYLATION
        
        LIPIDATION
        
        ACETYLATION
        
        DISULFIDE BOND
        
        UBIGUITINATION
  - - - Based on relative polarity of side chains (R).
        
        Indicates their tendency to react.
        
        Range from very nonpolar to very polar. --> Non-polar- equal number of amino gp & carboxyl gp (neutral).
        
        Some amino acids have very hydrophobic (nonpolar) side chains.
        
        Others more hydrophilic with polar but uncharged R groups.
        
        Most hydrophilic amino acids are polar with side chains with either negative or positive charge at physiological pH (~7.4).
        
        NONPOLAR
        
        Aliphatic- non aromatic, carbon atom forms straight-chains, branched chain or cyclic.
        
        Aromatic- organic compound with one/more benzene rings
        
        Electrons are shared equally between C and H, cannot form hydrogen bond with water.
        
        P/pro- ring involving α-carbon & α-amino group.
        
        POLAR
        
        UNCHARGED
        
        Asp & Glu- contain amide gp (carbonyl linked w a N atom)
        
        Ser & thr – has hydroxyl gp
        
        Both amide & hydroxyl gp allows formation of hydrogen bonds with water
        
        CHARGED
        
        +VE = BASIC | -VE = ACIDIC
        
        Positively or negatively charged groups can participate in electrostatic interactions with groups of opposite charge on other amino acids or other components.
        Asp & Glu - At physiological pH, the protons are dissociated & the side chain carry negatively charged (acidic)
        
        Electrostatic interaction between positively charged Lysine (+) and Asp (-ve)
      - pKa - property of a compound that tells us how acidic it is. (lower value- more acidic).
        
        pKa of the side chain (Asp & Glu) is about 4. When pH equals pKa, the protonated (uncharged) molecules equals the charged molecules
    - - Measure of quality , its ability to to provide essential amino acids for tissue maintenance.
        
        BV for whole egg is 100- most complete.
        
        Proteins from animal sources: high BV-contains all essential aa in proportion similar to those required for human. (except gelatine)
        
        Proteins from plant sources: Proteins from wheat, corn, rice and beans have lower biologic value than animals proteins.
        
        Combine to improve value; Wheat: lysine-deficient, methionine-rich Kidney beans: methionine-poor, lysine-rich.
        
        Animal proteins can complement biologic value of plant proteins: cereal & milk.
    - - Nitrogen balance- difference between amount of nitrogen taken into body (dietary proteins) and amount of nitrogen-containing compounds lost in urine, sweat, feces & cells that slough off.
        
        Dietary nitrogen – excretory nitrogen = 0
        
        Zero nitrogen balance.
        
        Or Dietary nitrogen = excretory nitrogen → Healthy adult.
      - Dietary nitrogen > Excretory nitrogen
        
        Positive nitrogen balance
        
        Growth
        
        Person is producing new tissue e.g during childhood, adolescence and pregnancy.
      - Dietary nitrogen < Excretory nitrogen
        
        Negative nitrogen balance
        
        Dietary deficiency of total protein or of one or more essential amino acids.
        
        Developes in 3 circumstances
        
        A person is eating too little protein.
        
        A person is eating protein that has too little of one or more of essential amino acids.
        
        During physiological stress – trauma, burns, illness, surgery. Body needs a complete complement of 20 aminoe acids to synthesize proteins.
        
        If essential amino acid is in short supply, total amount of protein made will be limited.
  - - - Mouth : no protein digestion just mechanical digestion
        Stomach: Begins in the stomach and completes in the intestines.
        
        Gastric HCl denatures the proteins, increasing surface
        Pepsin hydrolyses them into peptide fragments and free aas.
        
        Enzymes for digestion-zymogens (large inactive enzymes) produced by pancreas and released at the duodenum.
      - Enzymes enter lumen of digestive tract where they are cleaved to smaller active form – proteolytic activity.
        These enzymes have different specificity.
        
        No single enzyme can completely digest a protein.
        Proteins will be digested to small peptides and amino acids.
        
        aminopeptidases associated with intestinal epithelial cells will further cleaved peptides to di-,tri peptides & free aas .
      - STOMACH
        
        Parietal cells (epithelium cells of the stomach) secrete HCl.
        
        The acid will alter conformation of pepsinogen so that it can cleave itself producing active pepsin (autocatalytic).
        
        Dietary protein will be denatured at this pH but not pepsin.
        
        Pepsin will act as endopeptidase (hydrolyze peptide bonds within chains).
        
        Broad specificity but tends to cleave peptide bonds in which
        
        carboxyl group is provided by aromatic/acidic amino acid.
        Smaller peptides & free amino acids are produced.
      - PANCREAS
        
        SECRETION
        
        Bicarbonates – neutralizes the stomach acid.
        
        Zymogens which will be activated within a short time.
        
        Accomplished by trypsinogen → trypsin
        
        Cleaved by enteropeptidase (protease from brush border cells of intestines). --> Entero-related to intestines.
        
        Trypsinogen --> trypsin.
        
        chymotrypsinogen --> chymotrypsin
        
        proelastase --> elastase
        
        procarboxypeptidase --> carboxypeptidase
      - INTESTINAL
        
        Exopeptidase – produced by intestinal epithelial cells that acts within brush border.
        
        e.g. aminopeptidase – located on the brush border that cleaved one amino acid from the amino end.
        
        Intracellular peptidase – act on small peptides that are absorbed by the cells.
        
        Concerted action of proteolytic enzymes from stomach, pancreas & intestine cleaves dietary proteins to amino acids.
        
        They can digest themselves & intestinal cells regularly slough [sluff] off into the lumen.
    - - INTESTINAL
        
        Secondary active Na+-dependent transport (cotransport)
        
        Facilitated diffusion (special carrier protein channel).
        
        Transport linked to γ−glutamyl cycle
        
        Involved in transport of amino acid into cells of intestines and kidney.
        
        Extracellular amino acids reacts with glutathione (γ-glutamyl-cysteinyl-glycine). Enzyme- transpeptidase in cell membrane.
        
        γ-glutamyl amino acid is formed – travels across membrane to glutathione.
        
        Enzymes for glutathione synthesis are found in most tissues.
        
        But not for transpeptidase.
      - Cotransport of Na+ and amino acids.
        
        Amino acids are absorbed from lumen of small intestines by semispecific dependent transport proteins in luminal membrane of intestinal cell brush border.
        
        Cotransport of Na+ and amino acid from outside of apical membrane to inside of cell is driven by low intracellular Na conc.
        
        Low conc. results from pumping of Na+ out of the cell by a Na+, K+ -ATPase on the serosal membrane.
        
        This allows the cells to concentrate amino acid from intestinal lumen.
        
        The amino acids are then transported out of cell into interstitial fluid by facilitated transporters in the serosal side membrane.
        
        At least 6 different Na+-dependent amino acid carriers located in the apical brush border membrane.
        
        These carriers have overlapping specificity for different amino acids – neutral, proline & hydroxyproline, acidic amino acids, basic amino acids.
        
        Some amino acids are transported across luminal & serosal side of the membrane by facilitated transport carriers.
        
        Most amino acids are transported by more than one transport system.
  - - - Lack of essential amino acids – abnormalities in metabolism
        Inborn errors of amino acid metabolism- rare genetic (inherited) disorders in which the body cannot properly turn food into energy.
        
        The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food.
      - Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Leucine, Lysine, Arginine, Histidine
    - - from glucose (intermediates for glycolysis & TCA)
        
        Cysteine, Alanine, Glycine, Serine
        Aspartate, Asparagine, Glutamate, Glutamine, ProlinE, Arginine
      - Tyrosine require phenylalanine.
    - - Amino acid metabolism-part of nitrogen metabolism.
        
        Function of amino acid: as building blocks for protein synthesis & a source of energy.
        
        Precursor for nitrogen-containing compounds in the body e.g. neurotraansmitters, heme, purine & pyrimidines bases.
      - CONCEPTS
        
        AA POOL
        
        Aa released by hydrolysis of dietary/tissue protein mix with free aa distributed throughout the body (~100g).
        
        PROTEIN TURNOVER
        
        Most proteins are constantly being synthesized and then degraded.
        
        Hydrolysis of Dietary(~100g/day) & body proteins(~400g/day) releases amino acids to the amino acid pool.
        
        Maintained in the blood to ensure continuous availability of individual amino acids to tissues.
        
        Normal: same amount (~300-400g)of amino acid is needed for new protein synthesis & 30g for synthesis of other compounds.
        
        Degradation of protein is a continuous process.
        
        It is constantly being degraded to amino acids and resynthesized.
        
        In healthy adult, total amount of protein remains constant.
        
        Rate of turnover – varies widely between individuals.
        
        For example- digestive enzymes and plasma proteins degrades rapidly - have short half-lives i.e. hours or days (time required to lower its conc to half of the initial value).
        
        Structural protein –collagen metabolically stable with months or years of half-lives.
        
        Proteins with different half-lives doesn’t degrade in random.
        
        Chemical signals for protein turnover.
        
        They are chemically altered by oxidation or tagged with ubiquitin ( a small heat stable protein) – degrade faster.
        
        Proteins rich in sequences containing PEST (proline (P), glutamate (E), serine (S) & threonine(T)) – are rapidly degraded therefore exhibit short intracellular half-lives.
      - REMOVAL N FROM AA
        
        Transamination reaction
        
        transfer of A-amino gp to A-ketoglutarate. --> A-ketog. accept AA to become glutamate
        
        glutamate oxidatively deaminated after transamination @ use as amino donor --> synthesis nonessential AA
        
        aminotransferase transfer amino gp to pyridoxal --> generate pyridoxamine phosphate
        
        pyridoxamine form --> react w. A-keto acid --> form amino
        
        ENZ
        
        AMINOTRANSFERASES
        
        DISEASE
        
        Presence of elevated levels of aminotransferase in plasma indicates damage to cells rich in these enzymes.
        
        Liver diseases (severe viral hepatitis & prolonged circulatory collapse (failure of circulation, cardiac or peripheral) – plasma AST & ALT ↑.
        
        Serial enzyme measurements are useful to determine the course of liver damage.
        Nonhepatic diseases: Myocardial infarction & Muscle disorders.
        
        Serum glutamate pyruvate transaminases aka alanine transaminase (ALT).
        
        Normal level is 5-35 IU/L.
        
        Increased activity in liver diseases
        
        Serum glutamate oxaloacetate transaminase aka aspartate transaminase (AST)
        
        Normal level: 5-40 IU/L
        
        Increased activity is seen in heart diseases.
        
        Alanine aminotransferase (ALT)
        
        Aspartate aminotransferase (AST).
        
        Also known as Glutamate oxaloacetate transferase (GOT).
        
        Transfers amino group from glutamate to oxaloacetate to form aspartate.
        
        Requires Pyridoxal phosphate to form pyridoxamine phosphate.
        
        Pyridoxamine reacts with keto acid to for amino acid.
        
        Regenerate the ori form of pyridoxal phosphate.
        
        Oxidative deamination reaction
        
        Glutamate dehydrogenase
        
        Allosteric regulators - the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the allosteric site.
        
        ENZ
        
        D-amino acid oxidase
        
        Decarboxylation of amino acids.
        
        Carboxyl group (-COOH) is removed from amino acids as CO2.
        
        Enz: Glutamate decarboxylase.
        
        Requires pyridoxal phosphate.
        
        Produce amines – serves as neurotransmitters and hormones. E.g. glutamate-GABA,
        
        Histidine → Histamine by histidine decarboxylase,
        Tryptophan → Serotonin,
  - - - Cells in the body & bacteria in the gut releases N from amino acids as ammonia or ammonium ion (NH4+).
        
        NH4+ ⇔ NH3 + H+ pKa = 9.3,
        
        at physiological pH, conc of NH4+ is almost 100x more than NH3
        
        NH3 can cross cell membrane i.e. from kidney tubule cells to urine & decrease acidity of urine by binding to protons forming NH4+
      - The level of ammonia in the blood must be kept low.
        
        Normal ammonia conc in human plasma: 5-50 µmol/L (10-80 mg/dL)
        
        Slightly elevated level will be toxic to CNS.
      - SOURCE
        
        AA
        
        in many tissues esp liver.
        
        glutamate, reaction catalyzed by aminotransferase & glutamate DH
        
        Histidine – histidase
        
        serine & threonine – serine dehydratase
        
        asparagine - asparaginase
        
        GLUTAMINE
        
        renal glutaminase (Excreted in urine as NH4+, important in acid base balance --> NH3 decreases the acidity of urine by binding with proton.) , intestinal glutaminase (hydrolysis of glutamine. --> The mucosal cells obtain glutamine from blood or digestion), producing glutamate and ammonium ion (NH4+).
        
        BACTERIAL ACTION IN INTESTINE
        
        By bacterial degradation of urea in the lumen of intestines-urease.
        
        Ammonia is absorbed by portal vein & removed by the liver by conversion to urea.
        
        AMINES - from diet & monoamines which are hormones/NT that produces ammonia – action by amine oxidase.
        
        Catabolism of Purines and pyrimidines - Amino groups attached to the ring structure are released as ammonia.
      - TRANSPORT
        
        Ammonia is constantly produced but are present at low levels – rapid removal by liver & many tissues esp muscle release aa in the form of glutamine/alanine, not NH3.
        
        Urea – important disposal route of ammonia.
        --> Formed in the liver.
        --> Liver to kidney via blood, passes into glomerular filtrate
        
        GLUTAMINE
        
        Amide form of glutamic acid, provides nontoxic storage & transport form of NH3.
        
        Occurs primarily in the muscle, liver & nervous system.
        
        Major mechanism for removal of NH3 in the brain.
        
        Concentration in plasma higher than other aas.
        
        Removed by kidney and deaminated by renal glutaminase.
        
        Excreted into urine as NH4+.
        
        Maintain acid base balance in the body.
        
        Neurotoxicity.
        
        High levels of NH3- toxic to CNS.
        
        NH3 can cross blood brain barrier .
        
        In the brain, α-ketoglutarate combines with ammonia to form glutamate, catalyzed by glutamate DH.
        
        Depletion of α-ketoglutarate, essential intermediate in TCA cycle.
        
        Result: decrease cellular oxidation & ATP production.
        
        Brain depends on TCA cycle to maintain its high rate of energy production.
        
        a highly selective semipermeable membrane barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system (CNS)
        
        Hereditary hyperammonemia.
        
        Genetic deficiencies – 5 enzymes in urea cycle.
        
        Failure to synthesize urea --> mental retardation.
    - - Major disposal form of amino groups.
        
        Accounts for ∼90% of the N-containing components in the urine.
        
        One N is supplied by free NH3, and another N by aspartate.
        
        C&O derived from CO2.
        
        Produced in the liver, transported in the blood to the kidneys for excretion in the urine.
        
        Flow of N from amino acids to urea..
        
        Amino groups for urea synthesis are collected in the form of ammonia and aspartate.
      - UREA CYCLE
        
        Formation of carbamoyl phosphate.
        
        NH4+, CO2 and 2 ATP react to form carbamoyl phosphate.
        
        Enz: Carbamoyl phosphate synthase I (CPSI)
        
        Allosteric activator: N-acetylglutamate.
        
        Ammonium ion is provided by oxidative deamination of glutamate
        
        Note: CPSII participates in biosynthesis of pyrimidines, does not require N-acetylglutamate & occurs in cytosol
        
        Formation of citrulline.
        
        Carbamoyl phosphate reacts with ornithine to form citrulline.
        Enz: Ornithine trancarbamoylase.
        
        Citrulline is transported across the mitochondrial membranes and enters the cytosol.
        
        Synthesis of arginosuccinate
        
        Citrulline reacts with aspartate to produce arginosuccinate.
        Enz: arginosuccinate synthetase.
        
        Driven by hydrolysis of ATP to AMP & pyrophosphate (third ATP used).
        
        Cleavage of arginosuccinate.
        
        Enz: arginosuccinase to form fumarate and arginine.
        
        Fumarate is converted to malate (link to gluconeogenic pathway or regeneration of oxaloacetate).
        
        Cleavage of arginine to ornithine and urea.
        
        By arginase producing urea & regenerating ornithine.
        
        Ornithine is transported into the mitochondria for another round of the cycle.
        
        FX
        
        During fasting, liver maintains blood glucose level (gluconeogenesis).
        
        Carbon source – Aas from the muscle protein.
        AA nitrogens are converted to urea.
        
        Thus, urinary excretion of urea is high during fasting.
        
        As fasting progress, brain starts to use ketone bodies, sparing blood glucose.
        
        Less muscle protein is cleaved to produces aas for gluconeogenesis and decreased production of glucose from aa, less production of urea.
      - FATE
        
        Diffuses from liver
        
        Transported in the blood to kidney.
        
        Filtered by the kidney.
        
        Excreted in the urine.
        
        A portion of the urea synthesized in the liver diffuses from the blood into the intestine.
        
        Cleaved to CO2 and NH3 by bacterial urease
        
        These ammonia is partly lost in the feces and partly reabsorbed into the blood.
        
        Kidney failure- plasma urea levels are elevated, promoting greater transfer of urea to the gut – hyperammonemia, oral administration of neomycin to reduce population of bacteria.
      - REGULATION
        
        substrate availability
        
        Higher rate of ammonia production, higher rate of urea production.
        
        Characteristic of disposal pathway.
        
        Feed-forward regulation.
        
        Allosteric activation of CPSI by N-acetylglutamate (NAG) (rate limiting step).
        
        NAG is formed specifically to activate CPSI
        
        Acetyl CoA + glutamate → NAG
        
        Induction/repression of the synthesis of urea cycle enzymes.
        
        A high protein diet
        
        Prolonged fasting
        
        In both condition, aa carbon is converted to glucose, aa nitrogen is converted to urea.
        
        A typical type of feed-forward regulation.
  - - - GLUCOGENIC AA
        
        an amino acid that can be converted into glucose through gluconeogenesis.
        
        Amino acids that form Krebs/TCA cycle intermediates producing pyruvate which can be converted to glucose.
        
        Cycle intermediates: = α-Ketoglutarate, Succinyl CoA, Fumarate, Oxaloacetate
        
        Glucogenic amino acid functions to maintain normal blood glucose via gluconeogenesis.
        
        Gluconeogenesis – process where glucose is synthesized from noncarbohydrate precursors, occurs in the liver usually under fasting condition
        
        glucogenic AA = Alanine, Methionine, Cysteine, Valine, Glycine, Glutamine, Threonine, Glutamate, Serine, Proline, Asparagine, Histidine, Aspartate, Arginine
      - KETOGENIC AA
        
        an amino acid that can be degraded directly into acetyl-CoA, which is the precursor of ketone bodies.
        
        Ketone bodies are two water soluble molecules (acetoacetate, β-hydroxybutyrate) and their spontaneous breakdown product, acetone.
        
        Produced by the liver from fatty acids that are produced during periods of low food intake (fasting), carbohydrate restrictive diet, starvation, prolonged intense exercise, or in untreated (or inadequately treated) type 1 diabetes mellitus.
        
        Amino acids that can produce acetyl CoA and acetoacetyl CoA that can be converted to acetoacetate, acetone and β–hydroxybutyrate.
        
        Normal ketone bodies concentration in blood is 75 mg/dL.
        
        The value that exceed 75 mg/dL can cause ketonemia -the presence of an abnormally high concentration of ketone bodies in the blood..
        
        Therefore, ketone bodies may present in urine and causes ketonuria.
        
        During prolonged starvation, muscle, kidneys, heart and brain can metabolize ketone bodies (acetoacetate and β–hydroxybutyrate) to generate energy.
        
        Therefore, amino acids can be converted to acetyl CoA or acetoacetyl CoA.
        
        Amino acids which only produce acetyl CoA & acetoacetate and not glucose: Lysine & Leucine
      - GLUCOGENIC & KETOGENIC AA = Isoleucine, Phenylalanine, Tryptophan, Tyrosine
    - - BCAA
        
        branched chain amino acids are major aas which can be oxidized in muscle and most other tissues other than liver.
        
        However, all tissues can interconvert aas and TCA cycle intermediates via transamination reaction i.e.alanine↔pyruvate, Asp ↔ oxaloacetate & ketoglutarate ↔ glutamate.
        
        AA= Val, Leu and Ile contain non polar side chains. --> Methyl group branch.
        
        In mammalian, its initial catabolism reaction being performed by similar enzyme.
        
        Differ in the rest of the steps producing different products.
        
        Val as a glucogenic; Leu as a ketogenic; and Ile as both glucogenic and ketogenic.
        
        If BCAA in excess for protein synthesis, its transamination can occur (α-ketoglutarate; to equivalent branched chain α–keto acids).
  - - - HAEMOGLOBIN
        
        Transport O2 from the lungs to the tissue.
        
        Different in amino acid sequence but 3D structures are similar.
        
        STRUCTURE
        
        4 subunits
        
        4 haem groups (1haem-1O2)
        
        2 α-chains – 141 aa residues.
        
        2 β-chains – 146 aa residues.
        
        O2 TRANSPORT
        
        most O2 binds to hemoglobin --> oxyhemoglobin (HbO2).
        
        HbO2 release O2 in body cells region
        
        much O2 still bound to hemoglobin in venous blood
        
        Each O2 binds independently in each single molecule of myoglobin.
        
        For 4 subunits of haemoglobin – act cooperatively in O2 binding.
        
        Initially all 4 subunits are in T state (Taut/tense). – resist binding.
        
        As O2 binds to one subunit, the subunits change their conformation (R , relaxed state), increasing the chances of additional O2 binding.
        
        When amount of O2 in blood (pO2)is low, pO2 must increase considerably to permit initial binding. However once some O2 is bound, only small increases of pO2 cause large increases in percent of saturation of Hb with O2. result is sigmoidal curve.
        
        GRAPH
        
        Haemoglobin – sigmoidal curve. [Plot amount of O2 with *partial pressure of O2 (pO2). ]
        
        Both curve shows – when pO2 is high, both are saturated with O2.
        
        Haemoglobin is a good transporter – when pO2 is high in lungs, it binds to O2 and releases O2 when pO2 is low (tissue).
        
        Positive cooperativity – responsible for the sigmoidal oxygen saturation curve.
        
        REACTION W/ O2
        
        Hb4 + O2 ⇔ Hb4O2 (oxyhaemoglobin)
        
        Hb4O2 + O2 ⇔ Hb4O4
        
        Hb4O4 + O2 ⇔ Hb4O6
        
        Hb4O6 + O2 ⇔ Hb4O8
      - MYOGLOBIN
        
        Stores O2 in muscle cells – available for oxidation of fuel to produce energy for muscle contraction.
        
        STRUCTURE
        
        Single polypeptide – 153 aa residues
        
        Arranged in 8 α-helical regions.
        
        Polar residue – on surface
        
        Non-polar – interior molecule.
        
        1 haem group binds in hydrophobic pocket of protein containing 2 histidine residues.
        
        One of the histidine complexes with haem iron.
        
        O2 TRANSPORT
        
        Myoglobin – hyperbolic curve.
        
        At low levels, myoglobin contains more O2 than Hb.
        
        Whereas, at the tissue where pO2 is low, myoglobin still holds O2.
        
        Thus, in resting muscle, myoglobin binds O2 released in the blood by Hb.
        
        When muscle exercise, oxygen tension declines, then only myoglobin releases O2.
      - IMMUNOGLOBULIN
        
        Defence against invasion of the body by foreign organisms.
        
        It binds to the antigens on the invading organisms, initiating a process to inactivate and destroy.
        
        An antigen is a molecule that elicits the production of antibodies that are capable of binding to that specific antigen.
        
        STRUCTURE
        
        Each molecule contains 4 polypeptide chains.
        
        2 identical small light (L) chains
        
        2 identical large chains (H) heavy chains.
        
        Disulfide bonds join an L to an H chain.
        
        2 H chains are joined by disulphide bonds.
        
        CHO are attached to the H chains.
        
        Both L & H chains consists of variable (V) and constant (C) regions.
        
        Variable regions of L & H interacts, producing 2 regions at the end of the molecule which can bind to one antigen each.
        
        Thus a total of 2 antigen molecules can bind to one Ig.
        
        CLASS
        
        IgM - pentamer (snowflake, larger) -> 1st antibody release.
        
        readily fixes & activates complement
        
        IgA - monomer/dimer -> in mucus & other secretion.
        
        helps prevent entry of pathogen
        
        IgD - monomer attached to surface of B cells.
        
        fx as B cell receptor
        
        IgE - monomer active in allergies & parasitic infections.
        
        cause mast cell & basophils to release histamine
        
        B cell - swicth antibody class but retain antigen sp.
        
        IgM at firt -> IgG.
        
        almost all 2' response = IgG
        
        IgG - monomer -> 75% of antiboy in plasma (most abundant)
        
        fx as B cell receptor
        
        ANTIBODY RESPONSE
        
        PRIMARY
        
        antibody conc. rise gradually for 2 weeks after vacc. (contain dead/weaken organism --> stimulate body against them).
        
        B lymphocyte detects antigen on surface of organism in vaccine --> multiply & form clones (plasma cells @ memory B cells)
        
        plasma cell secrete antibody --> disable virus
        
        SECONDARY
        
        antibody conc rise quickly --> response more intense --> antibody conc remains higher for longer
    - - COLLAGEN
        
        Fibrous protein
        
        Major component of connective tissue. [Most abundant protein in mammals]
        
        Found in bone, tendons, skin, blood vessel and cornea of the eye.
        
        Contain 33% glycine, 21% proline and hydroxyproline (aa produced by posttranslational modification of proline residues)
        
        TYPES
        
        I - α1(I)2α2(I) --> Skin, bone, tendon, blood vessel, cornea
        
        II - [α1(II)]3 --> Cartillage, intervertebral disk, vitreous body (clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates).
        
        III - [α1(III)]3 --> Blood vessels, fetal skin
        
        IV - [α1(IV)]2α2(IV) --> Basement membrane.
        
        STRUCTURE
        
        Collagen consist of 3 polypeptides – α-chains.
        
        Variations in amino acid sequence of α-chains result in structural components that are about the same size but with slight different properties.
        
        These α-chains are combined from various type of collagen found in the tissue.
        
        Basic unit of collagen fiber (precursor)- tropocollagen.
        
        Triple helix of 3 polypeptide chains, twisted around each other, each with 1000 residues.
        
        The 3 polypeptide are linked by hydrogen bonds.
        
        3 fold helical structure.
        
        Each turn contains 3 aa residues.
        
        Repeat sequence of -Gly-X-Y-
        
        X- often proline
        
        Y-hydroxyproline or any other amino acids found in collagen.
        
        BIOSYNTHESIS
        
        Genes for pro-α-chains are transcribed
        
        mRNA translated into prepro- α polypeptide chains, extruded into ER, signal sequence is removed.
        
        Selected proline and lysine residues are hydroxylated.
        
        Selected lysine residues are glycosylated with glucose ∙and galactose
        
        3 pro-α-chains assemble intra and inter-chain disulfide bonds form at C-terminal propeptide extension.
        
        Triple helix forms by zipper-like folding.
        
        Procollagen molecule secreted from Golgi vacuole to extracellular matrix.
        
        N-terminal & C-terminal propeptides cleaved by procollagen peptidases.
        
        Hydroxylation of proline and lysine.
        
        Requires ascorbate (vitamin C).
        
        Occurs after protein has been synthesized.
        
        Hydroxyproline stabilizes triple helix
        
        Hydroxylysine – sites of attachment of carbohydrate moieties.
        
        DISEASE
        
        SCURVY
        
        Severe vitamin C deficiency results in scurvy .
        
        Affects tissues rich in collagen.
        
        Proline and lysine are not hydroxylated, hydrogen bonding in triple helices & cross linking between triple helices could not occur.
        
        Collagen becomes unstable.
        
        Scurvy is characterized by bleeding gums, loose teeth, skin lesions and weakened blood vessel walls.
        
        Ehlers-Danlos syndrome
        
        Inhereted defects in collagen molecule.
        
        Characterized by streachy skin and loose joints.
        
        Due to any one of several enzyme deficiencies in collagen biosynthesis
        
        Osteogenesis imperfecta
        
        Also known as brittle bone disease.
        
        Bones are easily bend and fracture.
        
        Retarded bone healing and rotated and twisted spine leading to a humpback appearance
        
        Due to mutation in type 1 collagen
      - ELASTIN
        
        Connective tissue protein with rubber-like properties.
        
        Found in lungs, walls of large blood vessels & elastic ligaments.
        
        Can be stretched several times their normal length.
        
        And can recoil back to original shape when force is relaxed.
        
        STRUCTURE
        
        Amino acid composition – small, nonpolar aa residues – glycine, alanine and valine.
        
        Also rich in proline and lysine but little hydroxyproline & no hydroxylysine.
        
        Interchain cross-links ; 4 lysine side chains can joined covalently to produce desmosine cross-link.
        (Allysine-derivative of lysine)
        
        BIOSYNTHESIS
        
        Hereditary elastin synthesis deficiency – leads to fetal hypokinesis (abnormally diminished muscular function or mobility) and/or akinesis (lack of motion) which eventually leads to death.
        
        Pathogenesis (the origination and development of a disease): minimal formation of elastin fibres is accompanied by abnormally increased cross linkage of collagen fibers.
- - - - organic comp that are poorly soluble in water but readily soluble in non polar organic solvents
        
        simplest lipid = fatty acids
        
        straight hydrocarbon chain terminating w/ carboxylic acid gp
        
        mainly as ester in natural fat & oil
        the chain may be saturated @ unsaturated
      - characteristics
        
        non polar / amphipathic
        
        high energy value
        
        fat soluble vitamins
        
        essential fatty acids
        
        store in adipose tissue --> thermal insulator
        
        electrical insulator --> propagation of depolarisation waves
        
        lipoprotein --> transport lipid
    - - simple
        
        ester of FA
        
        fat
        
        ester of FA and glycerol
        
        wax
        
        ester of long chain FA and long chain alcohol
      - complex
        
        ester of FA & -OH contain other gp
        
        phospholipid- a phosphoric acid residue & other substituent.
        --> eg: glycerophospholipid, spingophospholipid
        
        glycolipid- contain carbohydrate
        
        lipoprotein- lipid in association w/ protein
      - derived
        
        composed of hydrocarbon rings & long hydrocarbon side chain
        
        FA, glycerol, steroid, fatty aldehyde, ketone body, hydrocarbon, lipid-soluble vit, hormone
      - saturated
        
        solid at room temp, straight & stiff
      - unsaturated
        
        FA w/ multiple [=] have multiple bends.
        
        [=] change shape of fatty acid by making them bend.
        
        MORE [=], MORE fluid they are
        
        LONGER the length of hydrocarbon tail of sat. FA, HIGHER melt. point
      - essential
        
        required in human diet = cannot be synthesised by body.
        
        closely related: Omega-3 & Omega-6
        
        EFA: A-linolenic acid (18:3) & Linoleic acid (18:2) --> both are 18-C UFA
        
        human lack desaturase enz for their production [only in PLANT]
        
        human incapable of forming [=] beyond 9-C in chain
        
        FA chain elongated by enzymatic add' of 2Cs at COOH end
        
        present A-linolenic acid --> body make stearidonic acid [SDA], eicosatetraenoic a. [EDTA], eicosapentaenoic a. [EPA], docosahexaenoic a. [DHA]
        
        present linoleic acid --> G-linoleic a. [GLA], dihomo-G-linoleic a. [DGLA], arachidonic acid [AA]
    - - most form of stored body fat.
        
        highly concentrated form of energy (95% of diet fat)
        
        composed of trihydroxy-OH (glycerol) --> attached 3FA by ester bond
      - exist as fat (solid) / oil (liquid) at room temp depend' on comp's nature.
        
        contain HIGH proportion of short chain FA or UFA --> liquid at RT
        
        SFA of longer chain length have HIGH melt' point & solid at RT
        
        when used, FA released in FFA from triacylglycerol in adipose tissue by act' of lipase --> ffa transport by albumin to tissues for oxidation
    - - sterol & steroid
        
        comp of 1/> hydroxyl gp & no carbonyl / carboxyl.
        
        exist in free form @ -OH gp can be esterified w/ FA
        
        found in PLANT
        
        5% of diet lipid
        
        steroid
        
        4-ring core struct. resembl' phenanthrene to which cyclopentane ring is attached
      - cholesterol
        
        essential comp of cell mem..
        
        meats, egg yolk, dairy product.
        
        precursor for imp. steroid in body [bile acid, sex hormone, adrenocorticol h. vit D of animal tissue, cholecalcifeerol]
      - phospholipid
      - phosphatidylcholines
      - sphingolipid
      - sphingomyelin
      - glycolipid
  - - - ENZ
        
        LIPASE
        
        lingual & gastric lipase hydrolyse short & medium chain FA (<12 C) --> but not very effective
        
        most fat ends up in duodenum as small globules & bile is used to aid further digestion
        
        active in children
        cow's milk- HIGH short & medium chains
        
        PANCREATIC
        
        secreted w/ colipase & bicarbonate.
        
        bile salts coating the substrate. Inhibits lipase act.
        
        COLIPASE: relieve bile salt inhibition by binds to dietary fats & lipase --> enables TG to enter active site of lipase.
        
        BICARBONATE: neutralise acidic pH --> stimulated by secretin
        
        hydrolyse TG --> FFA + 2-MG
        
        product of digestion (FA + 2-MG) = packed in micelles by bile salts to travel through a layer of water to microvilli on surface of intestinal epithelial cells, where FAs + 2-MG are absorbed but the bile salts are left in gut lumen
        
        C4 - C12 do not require bile salts for the absorption.
        
        Directly absorbed into intestinal epithelial cell --> enter portal blood --> transported by bound to albumin
        
        resynthesis of TG occur in intestinal epithelial cells by esterification btw FA + 2-MG
        
        activation to fatty acyl CoA + 2-MG = DG + FA CoA = TG
        
        TG is packaged in chylomicrons for secretion into lymph
        
        Pancreatic Phospholipase A2 - phospholipid --> FFAs + lysophospholipid
        
        Pancreatic Esterases- cholesterol ester --> cholesterol
      - chylomicron
        
        SER produce TG from FA + 2-MG.
        
        RER produce apoprotein B-48.
        
        assembly of TG, apoprotein, phospholipids, cholesterol ester, fat sol. vit. occur in ER & Golgi C
        
        TRANSPORT
        
        nascent chylomicron accept ApoCII and ApoE from HDL --> mature chylomicron
        
        ApoCII acts as an activator of lipoprotein lipase (on capillary endothelial cells) at muscle & adipose tissue that digest TG of chylomicron & VLDL in blood
        
        ApoE is recognised by membrane receptors [hepatocyte] to enter these cells for digestion by lysosomes
        
        remain chylomicron in blood after LPL digestion is called chylomicron remnant
      - clinical
        
        lipid malabsorption
        
        chronic pancreatitis --> LOW lipase
        
        bile duct obstruction --> cholelithiasis, ca head of pancreas
        
        chronic liver disease --> liver cirrhosis
        --> steatorrhoea - bulky, fatty stool
  - - - a macromolecule = lipid + protein (apoprotein).
        
        transport lipid in blood
        
        surface- cholesterol, PL, protein
        
        core- TG, chol. ester
      - fx apoprotein:
        
        activate certain enz req for normal lipoprotein metabolism
        
        lipid transport protein
        
        ligands for interaction w/ lipoprotein receptors in tissues & receptors
      - types
        
        chylomicrons, VLDL, IDL, LDL, HDL.
        
        metabolism of VLDL --> IDL + LDL
        
        metabolism of chylomicrons --> chylomicron remnants
      - composition
        
        density HIGH w/ HIGH protein content & LOW TG content
        
        largest and least dense - rich in TG
        
        synthesised in intestinal mucosal cells - carry diet lipids
        
        contain apoB-48, chol., fat-sol. vit.
        
        secreted into lymphatic sys by exocytosis
        
        carry via lymphatic sys - thoracic duct into systemic blood circulation
    - - synthesise in liver.
        
        contain lipid comp (brought by chylomicron remnants), apoprotein B100
        fx: carry exo- & endogenous lipid from liver to extrahepatic tissue
      - synthesis protein in rer.
        
        protein combines w/ TG --> VLDL in golgi
        
        VLDL carry to cell mem. in vesicles and secrete by exocytosis
      - in blood circulation
        
        VLDL receive apoE and apoC-II from HDL --> mature VLDL
        
        chol. ester from HDL transferred to VLDL by cholesteryl ester transfer protein (CETP)
        
        act by lipoprotein lipase, TG --> FA + glycerol + remnant VLDL
        
        50% VLDL remnant taken up from blood by liver cell through apoE binding
        
        50% form IDL --> IDL lose some TG, ApoC & apoE to form LDL
    - - contain high % of chol. & chol. ester.
        
        FX: carry chol to extrahepatic tissue
        
        receptor of LDL on cell surf recognise apoB-100 in LDL & internalises by endocytosis
        
        internalised LDL is acted by lysosomal enz
        
        results in release of chol. --> inhibit HMG CoA reductase act' & decrease synthesis of HMG-CoA R (inhibit chol. synthesis)
  - - - FA synthesised by liver (cytosol) -> endogenous FA.
        
        synthesised from acetyl CoA when EXCESS.calorie intake, carbo, protein
        
        GLUCOSE = major source for lipogenesis
        
        FA exist as FFA, triacylglycerol (major storage form in ADIPOSE) & cholesterol esters, phospholipid, sphingolipid
      - EXCESS glucose --> pyruvate--> enter mitochondria--> form acetyl CoA (cannot cross mitochondrial m/brane)
        
        Acetyl CoA condense w/ oxaloacetate --> citrate [citrate shuttle] --> transport out to cytoplasm
        
        HIGH Acetyl CoA--> pyruvate dehydrogenase = inhibited & pyruvate carboxylase = stimulated
        
        HIGH OAA --> citrate= formed --> Acetyl CoA LOW --> PD activated & PC inhibited
      - PROCESS
        
        A. Conversion Acetyl CoA --> Malonyl CoA
        
        B. FA synthase comp reaction
        
        FA add 2C from M CoA --> palmitate.
        
        growing chain undergo 2 reduction that require NADPH
        
        loading-> condensation [acetoacetyl acyl carrier protein -> reduction [B-ketoacyl gp] -> dehydration -> reduction of double bond
        
        palmitate & other FA can be desaturated --> unsaturated FAs.
        
        in LIVER- FA = activated fatty acyl CoA [interact w/ glycerol 3-phosphate --> triacylglycerol --> packed into VLDL --> secreted to circulation]
        
        B-oxidation of new FA -> acetyl CoA is prevented by M CoA
        
        M CoA inhibits carnitine: palmitoyltransferase (enz to transport LCFA into mitochondria)
        
        Acetyl CoA carboxylase activated--> HIGH M CoA --> FA oxidation inhibited & FA synthesis= proceeding --> prevent futile cycle
        
        C. elongation of FA
        
        activated --> palmitoyl CoA.
        
        Malonyl CoA as 2Cdonor.
        
        require NADPH to stearyl CoA 18C
        
        D. Desaturation of FA
        
        occur in ER.
        
        use molecular O2.
        
        human desaturases cannot introduce [=] btw C9 & methyl end
      - regulation
        
        phosphorylation-dephosphorylation
        
        insulin activate phosphatase [dephosphorylates acetyl CoA carboxylase
        
        dephosphorylated form= active
        
        glucagon & Epinephrine inhibits by phosphorylating acetyl CoA carboxylase [phosphorylation by cAMP dependent protein kinase A]
        
        induction/repression of synthesis
        
        HIGH insulin: glucagon ratio causes induction of acetyl CoA carboxylase & FA synthase
        
        allosteric modification
        
        stimulated by citrate & inhibited by palmitoyl CoA
    - - active in liver & adipose tissue.
        
        in LIVER, glycerol 3-P is produced byglycerol kines and DHAP from glycolysis but adipocyte lack of glycerol kinase. [only store FA in fed state]
        
        FA --> fatty acyl CoA [thiokinase, CoA, ATP, AMP] --> react w/ glycerol 3-phosphate --> phosphatidic acid --> deP of phosphatidic acid --> diacylglycerol --> plus fatty acyl CoA --> triacylglycerol
    - - TG --> FA + glycerol.
        
        TG released from adipose tissue btw meals, overnight fasting, strenuous exercise
        
        derived from diet lipid & TG synthesised in liver
        
        oxidise long-chain FA = palmitate, oleate, stearate
        
        activated by low ration insulin and glucagon
        
        energy from FA oxidation
        
        initiated by hormone -sensitive lipase
      - of TG in adipose
        
        glycerol
        
        not degraded by adipose (no glycerol kinase).
        
        transported by blood to liver to be phosphorylated
        
        FA
        
        bind to albumin in plasma. - transported to tissue exc erythrocyte, brain
        
        oxidised for energy
  - - - transported in lipoprotein as free chol. & chol. ester. [1/3 FC, 2/3 CE]
        
        serve as stabilising comp of cell mem.
        
        a precursor of bile salts and steroid hormone
        
        obtained from diet / synthesised in cytosol
        
        precursor= acetyl CoA
        
        acyl CoA - chol. acyltransferase (ACAT) catalyse the covalent joining of cholesterol and long chain fatty acyl CoA to form chol. esters
      - cholesterol ester
        
        w/ FA chain.
        
        usually unsaturated FA.
        
        oleic acid = cholesteryl oleate
        
        linoleic = cholesteryl linoleate
      - source
        
        diet 40% [digestion & absorption - small intestine-->chylomicron]
        
        de novo synthesis 60%
        
        stage 1: synthesis of mevalonate from acetyl CoA.
        
        is committed step & rate-limiting step
        
        HMG-CoA synthase is in the cytosol & is distinct from mitochondrial HMG-CoA synthase that catalyse HMG-CoA involves in production of KB
        
        reducing equivalent: 2 NADPH
        
        stage 2: conversion of mevalonate to 2 activated isoprene.
        
        3P transfer to mevalonate to activate C5 and OH at C3 for further reaction
        
        P attached to C3 OH
        
        remove P at C# and COOH at C1
        
        produce [=] at 5C product
        
        stage 3: condensation of 6 activated 5C isoprenes to form 30C squalene
        
        stage 4: conversion of squalene to 4 ring steroid nucleus
      - de novo regulation [HMG CoA reductase]
        
        transcriptional control.
        
        synthesis mRNA HMG-CoA reductase = controlled by family of sterol regulatory element-binding proteins (SREBPs)
        
        SREBPs bind to SRE --> enhance transcription --> increase hMG CoA reductase synthesis
        
        Proteolytic degradation of HMG-CoA reductase
        
        HIGH chol. in cell --> change oligomerisation of mem. domain of HMG CoA R
        
        HIGH degradation --> LOW activity
        
        covalent modification
        
        by phosphorylation & dephosphorylation
        
        HMG CoA R = activated in dephosphoryylated state, inactive in dephosphoorylated state
        
        hormonal
      - lifestyle modification
        
        diet
        
        exercise
        
        stop smoking
        
        drug therapy
        
        mevinolin, mevastatin, lovastatin
        
        nicotinic acid
        
        clofibrate, gemfibrozil, fenofibrate
        
        probucol
        
        cholestyramine / colestipol
      - disease
        
        familial hypercholesterolaemia
- - - - CENTRIC
        
        OCCLUSION
        
        RELATION
      - RELATIONSHIP
        
        STATIC
        
        FUNCTIONAL
    - - FX: Chewing ■ Swallowing ■ Speaking ■ Stability ■ Appearance
      - MASTICATORY SYSTEM
        
        dental arch
        
        teeth are arranged within arch --> form size & shape (alveolar bone, basal b. general arrangement of teeth, cusp ridge, max convexities)
        
        classification
        
        u-shaped, parabolic, hyperbolic, ovoid, trapezoidal, omega shape - catenary
        
        arch length, depth, width. - max arch larger - overlaps
        
        tooth form
        
        tmj
        
        muscle
        
        neuromuscular act
        
        opposing tooth contact
      - INTRA-ARCH TOOTH
        ALIGNMENT
        
        alignment
        
        contact area
        
        contact point
        
        crest of curvature on proximal surf of tooth crowns
        
        ideal alignment
        
        incisal third/ midd third/ jxn btw incisal-midd 3rd
        
        viewed from labial/buccal- level of contact move from incisal 1/3rd to midd 1/3rd
        
        viewed from occlusal- lingual embrassures larger than buccal
        
        WHY?
        
        To stabilise the tooth --> stabilise dental arches.
        
        to prevent food impaction
        
        to protect interdental papillae
        
        embrasure
      - INTER-ARCH TOOTH
        ALIGNMENT
        
        Occlusion – contact of the chewing area and incising surfaces – maxillary and mandibular
        
        to occlude - to close
        
        contact btw upper & lower teeth
        
        intercuspal position: max contact btwopposing occlusal surf
        
        centric occlusion
        
        post teeth = cusp, fossa, marginal ridge
        
        ant teeth = incisal edge, lingual/palatal surf
        
        relationship
        
        Supporting cusp/functional cusp/working cusp
        ■ – maintaning distance between maxilla and mandible
        – Eg: buccal cusps of mandibular posterior teeth and palatal cusp of maxillary
        
        guiding cups
        
        Why this system:
        – To equalise the force of impact
        – To distribute load
        – To preserve integrity of the arch
    - - elevation, depression, lateral excursion, retraction, protraction
  - - - CENTRIC RELATION- the position of condyle at most sup and post in articular fossa
        --> most retruded position
        
        CENTRIC OCCLUSION - intercuspation or contact attained btw max & man post teeth
        --> 'intercuspal position'
        
        MAX INTERCUSPAL POSITION - max & man teeth surface contact w/ each other
        
        RESTING POSITION - habitual position of mandible when patient resting upright
        --> equal force acting on man
  - - - CLASSIFY
        
        PAROTID
        
        LOCATION: deep space, below the external auditory meatus, behind ramus of mandible & in front of sternocleidomastoid.
        
        DIVISION
        
        SUPERFICIAL & deep lobes by FACIAL NERVE
        
        SUBMAN.
        
        LOCATION: -Post part of floor of mouth, Adjacent to medial aspect of mand & Wrap around post aspect of m/hyoid m.
        
        DIVISION
        
        SUPERFICIAL & DEEP PARTS by mylohyoid
        
        SUBLINGUAL
        
        LOCATION: at ant part the floor of mouth, within sublingual fold , close to midline.
        
        EXCRETORY DUCT: Rivinus , Bartholin
      - HISTOLOGY
        
        PRIMARY SALIVA: production of saliva
        
        ACINUS
        
        MUCOUS
        
        RER: packed basally & laterally
        
        NUCLEUS: spherical
        
        GOLGI: < prominent
        
        SECRETORY GRANULES: < fused w/ 1another
        
        INTERDIGITATION BET CELLS:>
        
        INTERCELLULAR CANALICULLI:> size
        
        glycoprotein a.k.a mucins (which the structure of protein core predominantly O-linked)
        
        SEROUS
        
        RER: limited at basal cytoplasm.
        
        NUCLEUS: compressed
        
        GOLGI: large & > prominent
        
        SECRETORY GRANULES: < fused w/ 1another
        
        INTERDIGITATION BET CELLS: <
        
        INTERCELLULAR CANALICULLI: lacking
        
        serous glycoproteins have N-linked oligosaccharide
        
        INTERCALATED DUCT
        
        SHAPE: short & cuboidal.
        
        NUCLEUS: centrally placed.
        
        RER: small amount
        
        GOLGI: small
        5: SECRETORY GRANULES: < at apical cytoplasm
        
        BASAL STRIATION: absent
        
        MODIFIED PRIMARY SALIVA: passage of saliva
        
        production & modification of saliva
        
        STRIATED DUCT
        
        SHAPE: columnar
        
        NUCLEUS: centrally placed.
        
        RER: > amount
        
        GOLGI: small
        5: SECRETORY GRANULES: < at apical cytoplasm
        
        BASAL STRIATION:present due to elongated mitochondria
        
        EXCRETORY DUCT
        
        mainly: STRATIFIED columnar. occasionally: PSEUDOSTRA. EPI
        
        MYOEPITHELIAL CELL
        
        LOC: -secretory end piece (acinus),
        
        intercalated duct
        
        MORPHO:
        
        SECRETORY END PIECE- appear like ‘octopus sitting on a rock’ (few processes radiate fr central body
        
        INTERCALATED DUCT - appear spindle shaped.
        
        FX: contractile action  helps in salivary flow.
      - EMBRYOLOGY
        
        PAROTID GLD- 4-6th week
        
        SUBLINGUAL GLD- 8-12th week
        
        SUBMAN GLD- 6th week
        
        START
        
        INVAGINATION of oral epithelium
        into mesenchymal tissue
        
        SMALL BUD formation
        
        CLEFT
        
        BRANCHING MORPHOGENESIS
        --> successive generations of bud
        
        1 more item...
      - FORMATION
        
        SALIVA BICARBONATE (-Isotonic
        
        contain macromolecular components + water)
        
        RIBOSOMES -Attach to cisternae of rER & synthesize PROTEIN.
        
        translocate into RER
        
        packed into VESICLES
        
        transported to GOLGI C.
        
        PROTEIN undergo modification, condensation & packaging into SECRETORY GRANULE
        
        REACH MEMBRANE OF THE EPICAL END
        
        EXOCYTOSIS
        
        fused at cell m/brane
        (Contents release into lumen via exocytosis)
        
        stimulated by NE (symp. NT)
        
        bind to B-ADRENERGIC RECEPTOR
        
        activates G-PROTEIN
        
        activates ADENYL CYCLASE: convert ATP to cAMP
        
        activates PKA to phosphorilate protein & lead to exocytosis
        
        FLUID & electrolyte secretion- stimulated by binding of Acetylcholine (Ach) (parasymp. transmitter) to muscarinic cholinergic receptor (MC
        
        PROCESS
        
        FX: Increase luminal Cl- will be balanced by
        extracellular Na+ across tight junction & result in osmotic gradient
        
        The resulting osmotic gradient will lead to pull of
        water into lumen through tight junction & through cell via water channel.
    - - CHARATERISTIC
        
        Alkaline liquid secreted by the salivary glands and mucous membrane of the mouth.
        -Physical and chemical properties of saliva
        
        colourless
        
        viscous fluid
        
        Specific gravity of 1.002 to 1.008
        
        pH may vary from 6.4 to 7.3
        
        Resting saliva (pH 6.4 to 6.9)
        
        Stimulated saliva (pH 7.0 to 7.3)
      - COMP
        
        Whole saliva
        
        Is a mixture of secretions from major, minor salivary glands and gingival crevicular fluid (GCF)
        The composition of saliva depends on
        
        The secretory gland
        
        Whether the secretory gland is stimulated or not
        Unstimulated saliva
        
        The saliva which enters the mouth in the absence of exogenous/external stimuli (~ 0.3 ml/min)
        Stimulated saliva
        
        The saliva secreted in response to masticatory (chewing) or gustatory stimulation (citric acid)
        
        On average, saliva contains
        ~ 99.4% water
        ~ 0.6% solids
        
        Primary secretion (solids) contains
        65% organic
        35% inorganic salts
        
        Organic constituents:
        enzymes, albumin, globulins, mucin, uric acid, urea, amino acids and glucose
        
        Inorganic salts: Cl-, PO43-, SO42-, Na+, K+ and Ca2+
        
        Enzymes of human saliva
        
        Amylase (principle), lipase, lysozyme, maltase, protease and urease (plaque bacteria) .
        
        Salivary α-amylase -the S-type enzyme (secreted mainly by the parotid glands)
        
        A.k.a Ptyalin (Greek – spit)
        α-amylase (α-1,4-glycosidase)
        
        Hydrolyses of starch, glycogen and dextrins into glucose, maltose, maltotriose & mix of branched oligo
        
        Mainly in mouth ~ 5 to 6 min
        
        Active at pH>6, optimal pH is 6.8
        
        Inactivated in the stomach where pH falls to 3.0-4.0, food is well mixed with gastric juice.
        
        Lingual lipase
        
        important in the neonates (newborn <4weeks old)
        
        secreted by lingual serous glands
        
        to hydrolyse dietary fats in the stomach and small intestine of the neonates
        
        Proteolytic enzymes-protease.
        Lactoperoxidases – natural anti-bacterial agent.
        Antimicrobial agents: lysozyme & sIgA (saliva, colostrum etc)
        
        MUCIN
        
        Mucoprotein (glycoprotein with>40% CHO).
        
        Muco-mucus
        
        Secreted chiefly by the sublingual and the submandibular pairs
        
        Acts as a lubricant and facilitates swallowing of the food
      - IONIC COMP
        
        Calcium and phosphate
        
        helps to prevent dissolution of dental enamel
        Hydrogen carbonate
        
        offers the buffering capacity
        Thiocyanate
        
        provides antibacterial activity when converted to hypothiocyanate by salivary lactoperoxidase
        Na, K and Cl
        
        Major electrolytes, concentration varies at different flow rates
        Lead, cadmium and copper.
        
        Reflects the plasma concentration of these ions, consider as an index for pollutioN
        
        Urea - buffer, neutralizing acids formed by bacterial fermentation
      - FX:
        
        Formation of food bolus
        
        During mastication, it mixed with solid food material and changes it into a semi-solid form (food bolus)
        
        It moistens dry food and facilitates swallowing by lubricating action of glycoproteins
        
        Digestion of starch
        
        salivary α-amylase, digestion of polysaccharide
        
        is limited, when reach stomach, gastric acidity stops the action of salivary amylase.
        
        BUFFER
        
        Bicarbonate, phosphate and mucin
        
        keeps the mouth at neutral pH and protects the teeth from decalcification
        
        Bactericidal action
        
        It contains several proteolytic enzymes and antibodies
        
        It has protective effects against dental carries development
        
        Protection of teeth and gums against decay
        
        Tooth’s enamel continuously bathed in the saliva
        
        minerals exchange occur between enamel and saliva, enamel resistance to tooth decay
        
        Excretion
        
        A channel for excretion of toxic circulatory lead and mercury
        
        Urea, uric acid, ammonia, thiocyanate, iodine.
        
        Taste perception
        
        serves as solvent for the transport of molecules to reach the taste receptors in the taste buds
        
        Speech
        
        by keeping the mouth, lips and tongue moist, it helps in speech
        
        Vitamin B12 absorption
        
        At low pH of the stomach, most of the cobalamin is temporarily bound to a salivary protein, R protein
        
        At duodenum, R protein is degraded by pancreatic protease, B12 binds to intrinsic factor, IF-B12 is resistant to proteolysis, passes to distal ileum for B12 absorption
      - ENZ
        
        Salivary α-amylase
        
        Acidic residues and proline-rich residues.
        
        Primary substrate – starch (composed of amylose and amylopectin) producing maltose &dextrins that pass through stomach and small intestines. Further hydrolysed by pancreatic α-amylase (97% similarities).
        
        Maltose & dextrins pass thro intestinal epithelial cells to the brush border where α- glucosidases degrades them to glucose.
        
        Glucose – transported thro the cells & absorbed into the bloodstream
        
        β-amylase- synthesized by microorganism in the digestive track of animals/by plants. Function – digest the starch to produce maltose & glucose.
        
        ACIDIC PROLINE-RICH PROTEINS
        
        Acidic residues and proline-rich residues.
        
        1-81aa rich in AST & Glu.
        
        AA position 4 is Asn – phosphorylated.
        
        All acidic PRPs are hydrolysed at Arg 106 & the short C-terminal fragment is degraded
        
        Salivary agglutinin
        
        Highly conserved bacterial receptor glycoprotein.
        
        In lungs &saliva - Secreted protein (2394 aas) attached to diff bacteria including oral streptococci.
        
        Bacterial binding site-at domain 2 SRCR (14 scavenger receptor cysteine-rich domains)
        
        Part of innate immunity system to clear bacteria from oral cavity
        
        However, salivary agglutinin contributes to acquired pellicle. For individuals who secretes more agglutinin, binding of more bacteria contributes to increased risk of an adult’s susceptibility to caries.
      - FORMATION
        
        Salivary glands are largely composed of epithelial cells
        
        The fluid formation in salivary glands occurs in the end pieces
        --> Serous cells produce a watery seromucous secretion (acinar cells)
        --> Mucous cells produce a viscous mucin rich secretion (fluid or tubular cells)
        
        These secretions are modified by the end piece cells and ductal system before secreting into the mouth
        
        FILTRATION
  - - - Oral mucosa - oral mucous membrane – lines the oral cavity
        
        (like the skin – covering the external surface)
    - - protection
      - sensation
      - secretion
    - - oral vestibule
      - proper
      - boundaries
        
        ant: lips.
        laterally: cheeks.
        sup: palate.
        inf: floor of the mouth.
        Post: git
    - - masticatory
        
        Hard palate
        
        Gingiva
        
        epithelium
        --> moderately thick, keratinised [ortho-]
        --> inestensible
        --> jx btw epi-lamina prop = convoluted
        
        firm --> injection of loca anest = painful
      - lining
        
        cover = cheeks, inside lips, floor mouth, alveolar process, ventral side of tongue, soft palate
        
        subj to movement - flexible & stretching
        
        epi- thicker than mast mucosa, non keratinised & smooth interface
      - specialised
        
        • Dorsal part of tongue
        • Masticatory mucosa + lingual papillae (sensory function)
        • Composed of 2 parts (of different embryologic origin)
      - regional variation:
        
        Thickness of epithelium.
        
        degree of keratinization.
        
        complexity of CT-epithelium interface.
        
        composition of lamina propria.
        
        presence/absence of submucosa
    - - bone-> periosteum-> submucosa -> lamina propria-> epithelium [Stratified squamous]
    - - fungiform
        
        Scattered between filiform papillae
        
        Smooth Round
        
        Appears red – highly vascular connective tissue core
        
        Thin, nonkeratinized epithelium Taste buds – superior surface
      - filiforM
        
        Cover the entire anterior part of tongue
        
        Cone-shaped structure
        
        Thick, keratinized epithelium
        
        Compressing and breaking food
      - foliate
        
        leaflike
        
        Lateral part of tongue 4 to 11 parallel ridges ,
        
        alternate with deep grooves
        
        Taste buds present – lateral wall
      - circumvallate
        
        Adjacent and anterior to the sulcus terminalis 8 – 12
        
        Large structures
        
        Each surrounded by deep, circular groove
        
        Ducts of Ebner
        
        Keratinized epithelium on the superior
        
        Nonkeratinized epithelium on lateral with taste buds present
    - - MUCOCUTANEOUS JXN
        
        VERMILLION
        • Lacks the appendages of skin
        • Sebaceous glands may present
        • Epithelium : keratinized (thin, translucent)
        • Connective tissue papillae of the lamina propria are relatively long and narrow and contain capillary loops
        • Junction between vermillion zone and labial mucosa – intermediate zone – lacks granular layer , parakeratinized
        --> Infants – suckling pad
- - - - Oxidoreductase
        
        redox reaction
        
        Require the present of coenzyme, such as NAD+, NADP+ and FAD
        
        SUBCLASS [2ND DIGIT]: Dehydrogenase, 2. Oxidase, Reductase, 4. Peroxidase, Catalase, 6. Oxygenase, Hydroxylase
        
        1.1- DEHYDROGENASE
        
        Oxidation of alcohol to form aldehyde
        
        Removal of 2 e- and 2 H from alcohol, to produce aldehyde
        
        2 e- being transferred from NAD+ (reduced)/cofactor
        
        1.2 OXIDASE
        
        the transfer of 2 e- from donor to O2, to produce H2O2
        
        coenzyme flavin/metal
        
        1.3 PEROXIDASE
        
        utilize H2O2 rather than O2 as oxidant
        
        Catalysis: NADH peroxidase
        
        1.4 CATALASE
        
        unique; H2O2 as a donor & acceptor
        
        Will be utilize in the H2O2 detoxification
        
        1.5 OXYGENASE
        
        Incorporation of O2 to the substrate
        
        dioxygenase (O2 – single product);
        
        Monooxygenase
        --> O: as a hydroxyl
        --> O: be reduced to water by e- from substrate
      - Transferase
        
        to transfer functional groups between donor and acceptor
        
        Major moeity: amino, acyl, phosphate, 1-C, glycosyl group
        [methyl, hydroxymethyl, formyl, carboxyl, amino-transferase; kinase]
        
        SUBCLASS
        
        2.1 Aminotransferase
        
        transfer of amino group from 1 aa to the acceptor α-keto acid (transaminase)
        
        formation of new aa and α -keto acid
        
        2.2 Kinase
        
        transfer of γ phosphoryl group(labile) from ATP/nucleoside triphosphate to acceptor alcohol/amino gp
        
        The acceptor, such as glucose/protein
        
        eg. protein kinase A --> transfer of phosphate ATP to serine hydroxyl
        
        the transferred must be activated, becoming labile.
        
        .to form ester with ATP, “R” group is being transferred to the acceptor, to form new
        
        Hydrolase
        
        Donor group is being transferred to water
        
        general rxn: Hydrolytic bond cleavage C-O, C-N, O- P and C-S
      - Hydrolase
        
        SUBCLASS
        
        Esterase 2. Glycosidase 3. Peptidase 4. Phosphatase 5. Tiolase 6. Phosholipase 7. Amidase 8. Deaminase 9. Ribonuclease
        
        3.1 Peptidase - Proteolytic enzyme.
        3.2 Phosphatase
        
        Phosphate group exchange with hydroxyl group from water
        
        protein phosphatase vs. protein kinase
      - Lyase
        
        Addition, removal of water, ammonia and CO2 elements.
        
        Cleavage of C-C, C-O, C-N bonds.
        
        Other bonds: removal of double bonds, addition of group onto the [ = ]
        
        Decarboxylase 2. Aldolase 3. Hydratase 4. Dehydratase 5. Syntase (ATP absent) 6. Lyase
        
        4.1 Decarboxylase- Removal of CO2 from α keto acid OR
        β OR amino acid.
        
        4.2 Dehydratase- Removal of H2O in the dehydrated
        reaction.
      - Isomerase
        
        involving heterogenus enzyme group – many types of isomerization.
        
        Isomerization including cis-trans exchange and aldose-keto.
        
        SUBCLASS- Rasemase and epimerase, Isomerase & Mutase
      - Ligase
        
        Binding; synthesis reaction
        
        SUBCLASS= 1. Synthetase (ATP present) & 2. Carboxylase
    - - 2 PARTS
        
        Started with - 1 > substrate
        
        Followed by- type of reaction (-ase)
      - CATALYSE REDOX REACTION
        
        e- donor: alcohol
        
        e- acceptor: NAD+
      - EC
        
        Each enzyme contains Code Number (EC (Enzyme Commission) Number)
        
        4 digits (1: class, 2: subclass, 3: subsubclass, 4: specific enzyme)
        
        EG
        
        e.g.: EC 2.7.1.1
        
        (2: transferase, 7: phosphate transfer, 1: alcohol as phosphate acceptor, 1: hexokinase)
        
        adenosine triphosphate (ATP):D-hexose 6-phosphotransferase
        
        phosphate transfer from ATP to hydroxyl group at C6 of glucose
  - - - Allosteric binding sites --> Positive /negative effectors, Homotropic effectors (S), Heterotropic effectors
        
        Covalent modification --> Phosphorylation, Dephosphorylation, Protein kinase/phosphatase, Glycogen phosphorylase, Glycogen synthase
        
        Enzyme synthesis --> Regulate the rate, Induction (increase), Repression (decrease)
        
        Allosteric Control of Enzyme Activity --> Ligands (activators, inhibitors, substrates) & Ligands (effectors, modifiers, modulators)
        
        Covalent modification --> Regulate key enzyme activity, Phosphorylation, Dephosphorylation
        
        Multi-subunit enzymes (Regulatory subunit) (Catalytic subunit) --> Positive cooperativity (<Km) & Negative cooperativity (>Km)
    - - Compartmentation --> Limit enzyme activity & Regulate availability of substrates, products, cofactors etc.
        
        Covalent modification (Activators) (Inhibitors) --> Feedback inhibition & Cross Regulation
        
        Cellular Enzyme Concentration --> Short half-life of enzymes & de novo enzyme synthesis
      - METABOLITE FLOW EITHER ACTIVELY
        OR PASSIVELY REGULATED
        
        Most enzymes, the average intracellular concentration of their substrate tends to be close to the Km value.
        
        Substrate level is regulated passively for coordinating metabolite flow and maintaining homeostasis in quiescent cells.
        
        Actively regulated in response to internal and external signals.
      - FEATURE
        
        COMPARTMENTATION
        
        EG: Eukaryotes, protein degradation (lysosomes), fatty acid biosynthesis (cytosol), fatty acid oxidation (mitochondria)
        
        METABOLITE FLOW
        
        Controlling an enzyme that catalyzes a rate- limiting reaction regulates an entire metabolic pathway
        
        EG: Acetyl-CoA carboxylase, synthesis of malonyl-CoA
        (first committed reaction)
    - - ENZ QUANTITY
        
        CONTROL OF ENZ DEGRAD. - Protein turnover (the net result of enzyme synthesis and degradation);
        
        CONTROL OF ENZ SYN.
        
        Constitutive enzymes; [E] constant over time
        
        Inducers vs repressors – determine [E]
      - CATALYTIC ACT
        
        Allosteric effectors
        
        Aspartate transcarbamoylase (ATCase); 1st reaction to pyrimidine biosynthesis; feedback inhibitor, cytidine triphosphate (CTP)
        
        Allosteric & catalytic sites are spatially distinct
        
        Allosteric effects on Km or on Vmax
      - FEEDBACK REG - eg. Dietary cholesterol decreases hepatic synthesis of cholesterol, this feedback regulation does not involve FBI
      - NERVE IMPULSE - Hormone (1st messenger) bind to the cell surface receptors – induce the synthesis of specialized allosteric effectors cAMP (2nd messenger) (adenylyl cyclase roles in response to epinephrine and Ca2+)
    - - REVERSIBLE (Regulate key enzymes (ie. protein kinase/phosphatase) / IRREVERSIBLE
        
        Two most common forms --> Partial proteolysis (irreversible) & Phosphorylation (reversible)
        PROTEOLYSIS
        
        Proteases may be secreted as catalytically inactive proenzymes/zymogens
        
        Proenzymes facilitate rapid mobilization of an activity in response to physiologic demand
        
        Activation of prochymotrypsin requires selective proteolysis
        
        REVERSIBLE
        
        PROTEIN KINASE - Phosphorylate proteins by catalysing transfer of the terminal phosphoryl group of ATP to the hydroxyl groups of seryl, threonyl or tyrosyl residues forming O-phosphoseryl
        
        PROTEIN PHOSPHATASE - Hydrolytic removal of phosphoryl groups of the unmodified form of the protein.
        
        Protein phosphorylation is extremely versatile
    - - [S] & [P]
        
        •Velocity and [S]
        
        The Michealis-Menten Equation
        
        Hexokinase isoenzymes – Km for glucose
        
        Velocity and enzyme concentration
        
        Multisubstrate reactions
        
        Rates of enzyme-catalysed reactions in the cell
        
        Reversible Inhibition within the active site
        
        Competitive inhibition
        
        Noncompetitive and uncompetitive inhibiton
        
        Simple product inhibition in metabolic pathways
      - CONFORM CHANGE
        
        ALLOSTERIC ENZ
        
        Cooperativity in substrate binding to allosteric enzymes
        
        Allosteric activators and inhibitors
        
        Allosteric enzymes in metabolic pathways
        
        COV. MODIFI
        
        Phosphorylation
        
        Muscle glycogen phosphorylase
        
        Protein kinase A
        
        Other covalent modifications
        
        PROTEIN
        
        PROTEIN INTERAC.
        
        •Calmodulin-calmodulin family
        •G-protein
        
        •Proteolytic cleavage
  - - - Most enzymes require the presence of certain organic or inorganic substances for their activity.
        
        These are referred to as conjugated proteins.
        
        The protein part of such an enzyme is called apoenzyme (apoprotein).
        
        Whereas such enzymes are called holoenzymes.
        
        The nonprotein component of the holoenzyme is known as prosthetic group.
        
        Apoenzyme (protein) + Coenzyme (prosthetic group) = Holoenzyme.
        
        If the prosthetic group is removed, enzyme loses its biological activity.
        
        Prosthetic group: organic compound (coenzyme); inorganic ion (cofactor).
      - FEATURES
        
        Dialysable.
        
        Thermostable.
        
        Low-molecular weight organic substance.
        
        It is required with the enzyme to catalyse a highly specific group/type of reaction.
        
        Generally, derivatives of B complex group of vitamins.
      - RELATED VITAMIN
        
        Thiamine (B1) | TPP | Pyruvate --> Acetyl CoA α-Ketoglutarate --> Succinyl CoA
        
        Riboflavin (B2) | FMN & FAD | L-Amino acids --> α-Keto acids / Succinate --> Fumarate
        
        Niacin | NAD+ NADP+ | Lactate --> Pyruvate / Glucose-6-P --> 6-P-Gluconolactone
        
        Pyridoxine | Pyridoxal-5- P | Alanine + α-Ketoglutarate --> Pyruvate + Glutamate
        
        Pantothenic acid | CoA | Pyruvate --> Acetyl CoA / Fatty acid --> Fatty acyl CoA
        
        Biotin | Active biotin | Acetyl CoA --> Malonyl CoA / Pyruvate --> Oxaloacetate
        
        Folate | Tetrahydro- folate acid | Glycine --> Serine / Homocysteine --> Methionine
        
        B12 | Methylcobalamine | Methylmalonyl CoA --> Succinyl CoA / Homocysteine --> Methionine
        
        Lipoic acid | Lipoic acid | Pyruvic acid --> Acetyl CoA / α-Ketoglutarate --> Succinyl CoA
      - OXI-RED RXN
        
        FAD | Xantine oxidase | Xantine --> Uric acid
        
        NAD+ | Malate dehydrogenase | Malate --> Oxaloacetate
        
        Tetrahydrobiopterin | Phenylalanine hydroxylase | Phenylalanine --> Tyrosine
      - GP TRANSFER
        
        Pyridoxal- 5-P | Aspartate aminotrans- ferase | Oxaloacetate + Glutamate --> Aspartate + α-Ketoglutarate
        
        ATP | Hexokinase | Glucose --> Glucose-6-P
        
        S- Adenosylmethionine | Methyltransferase | Homocysteine --> Methionine
      - COV BOND FORM'
        
        Active biotin | Pyruvate carboxylase | Pyruvate --> Oxaloacetate
        
        UDP | Lactose synthase | UDP-Galactose + Glucose --> Lactose
        
        ATP | Glutamine synthetase | Glutamate + NH3 --> Glutamine
    - - Several enzymes require the presence of certain metal ions such as Mg2+, Zn2+ or Cl- for their activity.
        
        Such metal ions are called cofactors.
        
        A metal ion may be bound either tightly or loosely.
        
        These enzymes are referred to as metalloenzymes and metal-activated enzymes, respectively.
        
        METALLOENZYMES
        
        A metal ion may form an integral part of the enzyme. eg. zinc is an essential component of superoxide dismutase.
        
        Fe (Cytochromes, Peroxidase, Catalase) Cu (Ascorbic acid oxidase, Cytochrome oxidase, Tyrosinase) Mo (Aldehyde oxidase, Xanthine oxidase, Nitrate reductase) Zn (Carbonic anhydrase, Lactate dehydrogenase, Carboxypeptidase) Se (Glutatione peroxidase)
        
        METAL-ACT ENZ
        
        A metal ion may be loosely associated with the apoenzyme and form a metal-enzyme complex. eg. Cl- (as NaCl) acts as an activator for salivary amylase
        
        Ca (Lipase, ATPase, Succinate dehydrogenase) Co (Lecithinase, Peptidases) Mg (Phosphorylase, Enolase, DNA polymerase) Mn (Arginase, Phosphoglucomutase, Choline esterase) Cl (Salivary amylase) K (Pyruvate kinase)
    - - are physically distinct forms of an enzyme, which have the same specificity BUT differ from their --> Structure: Electrophoretic mobility & Immunological properties and source
      - LDH
        
        LACTATE DEHYDROGENASE = a tetramer.
        
        Four polypeptide subunits.
        
        Two types known as H (heart) subunit and M (muscle) subunit.
        
        LDH exists in serum in five distinct forms (isoenzymes) which have different proportions of H and M subunits.
        
        LDH1 has 4H type polypeptide chains or H4.
        
        LDH2 (H3M); LDH1 and LDH2 predominate in the myocardium and RBC.
        
        LDH1 becomes greater than LDH2 between 12 to 24 hours following myocardial infarction.
        
        LDH3 (H2M2), LDH4 (HM3) and LDH5 (M5).
        
        LDH1 and LDH2 predominate in the liver and skeletal muscle.
    - - CREATINE PHOSPHOKINASE referred to as creatine kinase (CK), exists in three forms.
        
        Each isoenzymes is a dimer composed of two subunits.
        
        Two types known as M (muscle) subunit and/or B (brain) subunit.
        
        CPK1 (BB), which is mainly found in the brain.
        
        CPK2 (MB) in the myocardium.
        
        CPK3 (MM) in the skeletal muscle.
        
        CPK2 is present in very small amount in the serum.
        
        Its level rises within 4 hours and reaches to a maximum within 1 day of myocardial infarction.
    - - ALKALINE PHOSPHATASE exists in three forms.
        
        Different tissues contain different form of the enzyme.
        
        A major portion of ALP in serum is derived from the liver.
        
        Its level rises in posthepatic jaundice.
        
        In growing children, the major isoenzyme is from the bone and is related to increased osteoblastic activity.
        
        During the last trimester of pregnancy, there is increase in ALP, which is of placental origin.
        
        This isoenzyme is heat-stable and is also called as heat-stable alkaline phosphatase.
- - - - Main energy provider e.g. fat, CHO & protein.
        
        Intake is larger than other dietary nutrients.
        
        FAT
        
        Most important form: Triacylglycerol, >90% of total dietary lipid.
        
        Supply essential fatty acids (Linoleic & linolenic acids)
        
        Increase palatability of food.
        
        Producing feeling of satiety.
        
        Required for absorption of fat-soluble vitamins.
        
        Plant source: TAG generally contains more unsaturated fatty acids than animal origin.
        
        Animal source: TAG more saturated than plants except fish
        
        Requirements: Dietary fat provides essential fatty acids (EFA)
        
        For fluidity of membrane structure & synthesis of eicosanoids (regulates metabolism-regulates blood pressure, cell growth, inhibits inflammation etc.).
        
        Deficiency: scaly dermatitis, hair loss & poor wound healing.
        
        Dietary goals: 30% of total calories
        
        CARBOHYDRATE
        
        CLASSIFICATION
        
        Monosaccharides – glucose (fruits) & fructose (honey & fruits)
        
        Disaccharides (simple sugars) --> Sucrose (table sugar), lactose (milk) and maltose (beer & malt liquors)
        
        Polysaccharides – complex CHO --> Polymers of glucose, do not have a sweet taste. Starch, potatoes & vegetables.
        
        Fiber --> Dietary fiber- non-digestible CHO,e.g. cellulose, lignin & pectin. Soluble fibers- found in oats, beans and legumes
        
        BENEFIT
        
        Adds bulkiness to food, absorb 10-15x its own weight in water, drawing fluid into lumen of intestines & increasing bowel motility.
        
        Binding properties of fiber – decreased absorption of toxic compounds- carcinogens.
        
        Decrease the risk of constipation (infrequent bowel evacuation), hemorrhoids (swelling& inflammation of the veins in anus&rectum) & colon cancer.
        
        Lowers blood cholesterol.
        
        Fiber can bind to trace elements (Zn2+) & decrease absorption of fat-soluble vitamins.--> Supplementation of diet with excess fiber is not recommended.
        
        Moderate increased amounts of fiber (20-35g/day) should be obtained from natural sources.
        
        CHO requirements: Not an essential nutrient but absence of dietary CHO leads to;
        --> Ketone bodies production
        --> Degradation of body proteins –amino acids provide carbon skeleton for gluconeogenesis.
        
        58% of complex CHO
        
        DISEASE
        
        NO direct evidence that consumption of simple sugars is harmful.
        
        Sugar is not fattening but can result in fat synthesis when consumed in excess of the body’s energy needs.
        
        Dental caries shows a strong correlation with the amount of sucrose consumed.
        
        PROTEIN
        
        Protein in food provides essential amino acids.
        
        10 of 20 amino acids needed for the synthesis of body proteins are essential.
        --> 8 are essential all the times
        --> 2 are required only during periods of rapid tissue growth (childhood) or recovery from illness.
        
        BV
        
        Measure of quality , its ability to to provide essential amino acids for tissue maintenance. BV for whole egg is 100.
        
        Proteins from animal sources: high BV-contains all essential aa in proportion similar to those required for human. (except gelatine)
        
        Proteins from plant sources: Proteins from wheat, corn, rice and beans have lower biologic value than animals proteins.
        
        Combine to improve value;
        --> Wheat: lysine-deficient, methionine-rich
        --> Kidney beans: methionine-poor, lysine-rich.
        
        Animal proteins can complement biologic value of plant proteins: cereal & milk.
        
        REQUIREMENT
        
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        NITROGEN BALANCE
        
        Amount of nitrogen consumed equals nitrogen excreted in the urine, sweat & feces.
        
        Most healthy adults are normally in nitrogen balance.
        
        Positive nitrogen balance: Nitrogen intake exceeds nitrogen excretion – children (tissue growth), pregnancy & during recovery from illness.
        
        Negative nitrogen balance: Nitrogen losses are greater than intake. – inadequate dietary protein, lack of essential amino acids or during physiologic stresses e.g. trauma, burns, illness or surgery.
    - - Nutrients needed in lesser amounts.
        
        MINERALS & VITAMINS
        
        Mineral- inorganic elements that serve a variety of functions.
        
        Cofactors in enzyme-catalyzed reactions, regulation of acid-base balance, in nerve conduction and muscle contractions.
        
        Every mineral is needed daily in certain amount μg - g.
        
        26 element known to be essential for animal organism.
        
        11 major element (macrominerals)- C, H, O, N, S, P, Ca, K, Na, Mg & Cl.
        
        Iron & Zink – in small but appreciable amounts.
        
        Trace amount (microminerals)- I, Cu, Mn, Co, Mo, Se, Cr, Ni, Si, Vd, & F. (some not conclusive to be essential)
        
        Calcium and phosphorus
        
        Most abundant minerals in the body
        
        2 forms of calcium – calcium phosphate crystals
        
        Unbound ionic form (Ca2+) – critical functions in muscle contraction, nerve impulse transmission, ion transport & transmission of signals across membranes.
        
        Iron (Fe)
        
        Wide range of biological functions: many are connected with oxidation reactions & energy conservation.
        
        Source: meat, liver, fish, egg, cocoa & chocolate. Significant amount in potatoes & green vegetables..
        
        Found in heme components of hemeproteins (mostly hemoglobins & cytochromes).
        
        Storage: ferritin & hemosiderin.
        
        Adult contains 4-5g iron, 70% in hemoglobin, 5% in myoglobin, 20% in storage & transport form & 5% in iron-containing enzymes.
        
        Iron deficiency: reduction of Hb synthesis & can result in iron-deficiency anemia.
        --> Most commonly seen in pre-menopausal women
        --> In men: undetected bleeding from gastrointestinal tract.
        --> Diet poor in iron or impaired iron absorption
        
        Excess iron: Adult men shouldn’t use iron supplement because high tissue levels of iron correlates with increased risk of myocardial infarction.
        
        Sodium, potassium and chloride
        
        High intake of potassium has a reverse effect as compared to the sodium intake.
        
        Diet with low sodium but high in potassium is associated with the lowest blood pressure level and low frequency of stroke.
        
        Ratio Na/K may be of greater significance than Na intake alone.
        
        Restriction of sodium intake significantly reduces the arterial blood pressure in 60% of people suffering hypertension but not always account for the development of this condition.
        
        Newly discovered natriuretic (secretion of sodium in urine) hormones/peptides, isolated from the atria of the heart – atrial natriuretic peptide ANP (28aa)
        
        1stly discovered in rats.
        
        Cause marked increase in sodium and water excretion.
        Another example- Brain natriuretic peptide (BNP)
    - - FAT SOLUBLE
        
        Only one has a coenzyme function-Vit K.
        
        Released, absorbed & transported with fat of the diet.
        
        Stored in liver & adipose tissue
        
        Not readily excreted in the urine
        
        Consumption of vit. A & D in excess can lead to accumulation of toxic quantities.
        
        VIT A (RETINOL)
        
        RDA: 800 RE (retinol equivalents) female, 1000 RE male.
        
        1 RE = 1μg of retinol, 6 μg of β-carotene or 12 μg of other carotenoids
        SOURCE:
        
        animal-butter, milk, egg yolk, liver, kidney, fish oil.
        
        Vegetables- yellow & dark green vegetables & fruits. Good source of carotenes (precursor of vitamin A).
        
        STRUCTURE
        
        RETINOL
        
        A primary alcohol containing a β-ionone ring with unsaturated side chain. Found in animal tissues as a retinyl ester with long chain fatty acid.
        
        RETINAL
        
        Aldehyde derived from the oxidation of retinol
        
        RETINOIC ACID
        
        Acid derived from the oxidation of retinal. Retinoic acid cannot be reduced in the body, therefore cannot give rise to either retinal or retinol.
        
        β-carotene: plant foods. Can be oxidatively cleaved in the intestine to yield 2 molecules of retinal
        
        In human, conversion is inefficient.
        
        FX
        
        VISUAL
        
        Vitamin A is a component of the visual pigments of rod and cone cells.
        
        Rhodopsin- visual pigment of the rod cells in the retina, consist of 11-cis retinal specifically bound to the protein opsin.
        
        When rhodopsin is exposed to light, a series of photoisomerizations occur, resulting in bleaching of visual pigment & release of all trans retinal & opsin.
        
        This process triggers a nerve impulse that is transmitted by the optic nerve to the brain.
        
        Trans retinol is isomerized back to 11-cis retinal, which combines spontaneously with opsin to form rhodopsin. Complete a cycle.
        
        Similar reaction for color vision in the cone cells.
        
        GROWTH
        
        Animals deprived of Vit. A initially lose their appetites. (keratinization of the taste buds).
        
        Bone growth is slow & fail to keep pace with the growth of nervous system, leading to CNS damage.
        
        REPRODUCTION
        
        Retinol & retinal are essential for normal reproduction, supporting spermatogenesis in male & preventing fetal resorption in female.
        
        Retinoic acid is inactive in maintaining reproduction & visual cycle, but promotes growth & differentiation of epithelial cells. Animals given vit.A only as retinoic acid from birth are blind & sterile
        
        Maintenance of epithelial cells: vit A is essential for normal differentiation of epithelial cells & mucus secretion.
        
        NIGHT BLINDNESS
        
        earliest sign of deficiency.
        
        Prolonged deficiency leads to irreversible loss in the number of visual cells.
        
        Severe deficiency leads to xerophthalmia (pathologic dryness of conjuctiva & cornea).
        
        If untreated, xerophthalmia results in corneal xerosis (dryness of the cornea) & ultimately blindness because formation of opaque scar tissue (cataracts)
        
        TRANSPORTATION
        
        Transport to liver: Retinol esters in the diet are hydrolyzed in the intestinal mucosa, releasing retinol & free fatty acids.
        
        Retinol derived from esters & from the cleavage & reduction of carotenes is reesterified to long-chain fatty acids in the intestinal mucosa & secreted as component of chylomicrons into the lymphatic system.
        
        Retinol esters in the chylomicrons are taken up & stored by the liver.
        
        Release from the liver: When needed, released & transported by plasma retinol-binding protein (RBP) to extra-hepatic tissue.
        
        Retinol-RBP complex attached to specific receptors on the surface of many cells of peripheral tissues.
        
        Many tissues contain a cellular retinol-binding protein(CRBP) that carries retinol to the sites in the nucleus where vit acts in a manner analogues to steroid hormones.
        
        CLINICAL
        
        DEFICIENCY
        
        Follicular hyperkeratosis a skin condition characterized by excessive development of keratin in hair follicles, resulting in rough, cone-shaped, elevated papules (a small pimple). The openings are often closed with a white plug of encrusted sebum (an oily secretion of the sebaceous glands).
        
        In the mouth- hyperkeratosis of the mucosa & salivary glands, subjected to hyperplasia (enlargement) of both acini (sack-like cavity in the gland) & ducts.
        
        Keratin plugs may obstruct the ducts.
        
        Reduced salivary flow- increased in caries susceptibility.
        
        DERMATOLOGY
        
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        EXCESSIVE
        
        Toxic syndrom – hypervitaminosis A. Amounts exceeding 7.5mg/day should be avoided.
        Early signs:
        
        dermatitis – dry & pruritic skin
        
        Liver enlarged - Hepatomegaly –& can become cirrhosis.
        
        In the nervous system – a rise in the intracranial pressure (might mimic symptoms of brain tumors.
        
        Severe headache, hyperirritability, vomiting, diarrhea, bone decalcification & skin lesions.
        
        Pregnant women- potential for causing congenital malformations in the developing fetus.
        
        VIT D
        
        RDA indiv 1-70yrs old: 15μg/day
        70yrs old: 20μg/day
        Source:
        
        Diet: Ergocalciferol (vit. D2) found in plants & cholecalciferol (vit. D3) liver oils of fish, egg yolk & fortified milk.
        
        Endogenous vitamin precursor: 7-dehydrocholesterol is converted to cholecalciferol in the dermis & epidermis of humans exposed to sunlight (wave length 290-310nm)
        
        Vit D precursor is a dietary requirement only to individuals with limited exposure to sunlight.
        
        FORMATION
        
        Vitamin D2 & D3 are not biologically active, but are converted in vivo to the active form by 2 sequential hydroxylation reactions.
        
        First hydroxylation occurs at 25th position, catalysed by specific hydroxylase in the liver.
        
        25-hydroxycholcalciferol- predominant form in plasma, also major storage form.
        
        25-OH D3 is further hydroxylated at position 1 by specific 25-hydroxycholecalciferol 1-hydrolase found in the kidney forming 1,25-diOH D3.
        
        FX
        
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        VIT E
        
        8 naturally occuring form, 4 tocopherols and 4 tocotrienols.
        
        α-tocopherol is the most active form.
        
        RDA: male 10mg, female 8mg.
        
        Source: vegetable oils (palm oil)-rich source of tocopherols & tocotrienols. liver & egg (moderate).
        
        Vit. E requirement increases as the intake of polyunsatured fatty acid increases.
        
        FX
        
        Anti-oxidant in prevention of the nonenzymatic oxidation of cell components. E.g. polyunsaturated fatty acids by oxygen & free radicals.
        
        Protection against heart attack by prevention of oxidation of LDL. Oxidized LDL is thought to promote heart disease.
        
        Supplements of 400IU (RDA is 15IU) per day for >2 years provides greatest protection. Approx. 40% reduction in the incidence of heart attact compared to those who took no supplements.
        
        Together with vitamin C & β-carotene- delay the onset of cataracts.
        
        ABSOP' & TRANSPORT'
        
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        VIT K
        
        no RDA, but adequate intake for
        
        Adult male: 120μg/day
        
        Adult female: 90 μg/day
        SOURCE:
        
        Diet: Green vegetables; cabbage, cauliflower, egg yolk, liver & cereal. Small amount in milk.
        
        Extensive synthesis by the intestinal bacteria.
        
        ‘Phylloquinon’ (vit. K1)synthesized by plants.
        
        ‘Menaquinone’ (vit K2) synthesized by bacteria.
        
        For therapy -menadione- synthetic derivatives of vit.K .
        
        FX
        
        Coenzymes in the carboxylation of certain glutamate acid residues, which is needed for the synthesis of prothrombin (factor II), VII, IX & X.
        
        Formation of γ-carboxyglutamate.
        --> Formation of clotting factors require the vitamin K-dependent carboxylation of glutamic acid residues forming a mature clotting factor that contains γ-carboxyglutamate (Gla) & capable of subsequent activation.
        --> The formation of Gla is inhibited by dicumarol & warfarin (anti-coagulant preventing blood clot).
        
        Interaction of prothrombin with platelets
        
        Gla residues of of prothrombin are good chelators of positively-charged calcium ions because of 2 adjacent, negatively charged carboxylate groups.
        
        The prothrombin-calcium complex is then able to bind to phospholipids essential for blood clotting on the surface of the platelets.
        
        Attachment to the platelet increases the rate of proteolytic conversion of prothrombin to thrombin.
        
        CLINICAL
        
        DEFICIENCY
        
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        EXCESSIVE
        
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      - WATER SOLUBLE
        
        VITAMIN C
        
        Ascorbic acid.
        
        RDA : male 90 mg/day, female 75 mg/day.
        
        Most animals have the synthesis pathway but not us.
        
        Source: citrus fruits (70mg), tomato(23mg), potatoes (19.3mg/100g), green vegetables, guava (163mg), mango (57mg) etc.
        
        ionized form : ascorbate
        
        Labile -easily destroyed by oxygen, metal ions, increasing pH, heat & light.
        
        FX
        
        Collagen synthesis, two hydroxylation reactions requiring vitamin C are necessary for collagen synthesis.
        
        Hydroxylation of selected proline residues on newly synthesized collagen alpha chains are necessary for the collagen molecule to aggregate into its triple-helix configuration.
        
        Hydroxylation of lysine residues permits cross-linking, glycosylation and phosphorylation.
        
        Hydroxylation of proline and lysine are catalyzed by hydroxylase.
        
        During hydroxylation reactions, vit C is a cofactor to keep iron in reduced state (Fe+2 ).
        
        Ascorbate reduces Fe+3 (ferric ion) back to Fe+2 (ferrous ion).
        
        Anti-oxidant property – supplementation of diet decreases the incidence of chronic disease such as coronary heart disease & certain cancers.
        
        Ability to inactivate toxic oxygen free radicals
        
        Reactive oxygen radicals arise from normal metabolism & by exposure to sunlight, ozone, smoking & other pollutants.
        
        Free radicals are known to damage lipid membranes, proteins & cellular DNA
        
        Tryptophan metabolism – hydroxylation of tryptophan to serotonin
        
        Tyrosine metabolism – helps in oxidation of parahydroxy phenyl pyruvate to homogentisic acid.
        
        Iron metabolism – Ascorbic acid enhances the iron absorption from intestine. Reduces Fe+3 to Fe+2 for better absorption.
        
        Folic acid metabolism – reducing folic acid to THFA
        
        Haemoglobin – reconversion of methaemoglobin to haemoglobin
        MetHb - a stable oxidized form of haemoglobin which is unable to release oxygen to the tissues, produced in some inherited abnormalties and by oxidizing drugs..
        
        Steroid synthesis- epinephrine & norepinephrine ( dopamine β-hydroxylase)
        
        In the process of phagocytosis = NADPH oxidase converts O2 to superoxide. --> Superoxide🡪H2O2 --> H2O2 🡪 OH- (hydroxyl radical),
        
        DEFICIENCY
        
        SCURVY
        
        –disease characterized by sore, spongy gums, loose teeth, fragile blood vessels, swollen joints & anemia.
        
        Many symptoms can be explained by deficiency in hydroxylation of collagen, resulting in defective tissue.
        
        Toxicity of ascorbic acid- no acute toxicity has been observed (Upper limit: 2000mg/day).
        
        Oxidized form – dehydroascorbic acid is toxic
        
        B-COMPLEX
        
        Although structurally unrelated but they tend to occur together in natural food.
        
        Deficiency of a single member is unlikely to occur.
        
        If a person appears to be deficient in one of the member, it is advisable that intake of all should be increased (rare).
        
        No storage for all except vitamin B12.
        
        Any excess will be excreted in the urine.
        
        B-complex vitamins are essential to the normal metabolism of all cells & are co enzymes in many reactions.
        
        COMPONENT
        
        Thiamin (B1) Riboflavin (B2) Niacin (B3) Pyridoxine (B6) Folic acid (B9) Cobalamine (B12) Biotin (B7) Panthotenic acid (B5)
        
        THIAMIN (B1)
        
        RDA: male 1.2mg/day, female 1.1 mg/day
        
        Source: Beef, Pork, liver, spinach, green peas, whole grains & legumes (outer layer of seeds).
        
        Active form: thiamin pyrophosphate (TPP).
        
        Formed by the transfer of pyrophosphate group from ATP to thiamin.
        TPP acts as coenzymes to;
        --> Pyruvate dehydrogenase (pyruvate to acetyl CoA).
        --> α-ketoglutarate dehydrogenase ( Oxidative decarboxylation) ketoglutarate to succinyl CoA.
        --> Transketolase (ribose 5-P to Glyceraldehyde 3-P)
        
        CLINICAL
        
        Oxidative decarboxylation of pyruvate & α-ketoglutarate plays a key role in energy metabolism of most cells, particularly important in nervous system
        
        When deficiency in thiamin, enzyme activity decreases, resulting in decreased production of ATP, thus impaired cellular function.
        
        Beri-beri - severe thiamin deficiency, found in areas where polished rice is the major component of the diet.
        
        - Wet beriberi- accumulation of tissue fluid (edema).
        - Dry beriberi- extreme emaciation (wasting of body-extreme weight loss & thinness.
        
        Both forms have nervous degeneration & often outcome is death from heart failure. Infantile beriberi- signs- tachycardia (rapid heart rate), vomiting, convulsion & if not treated death.
        
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        RIBOFLAVIN
        
        RDA: male 1.3 mg/day, female 1.1 mg/day
        
        Source: Milk, eggs, liver, green vegetables.
        
        2 ACTIVE FORM = Flavin mononucleotid (FMN), Flavin adenin dinucleotid (FAD) [Prosthetic group (coenzyme tightly bound to the enzyme).]
        
        FMN and FAD can reversibly accept two hydrogen atoms forming FMNH2 or FADH2
        
        Both are bound tightly/covalently to flavoenzymes i.e with dehydrogenase, oxidase, monooxygenase or reductase.
        
        Easily destroyed by the UV light.
        
        DEFICIENCY
        
        Deficiency is not associated with a major human disease, although it is frequently accompanying other vitamin deficiencies.
        
        Symptoms:
        --> Dermatitis – inflammation to the skin
        --> Chielosis – fissuring at the corners of the mouth.
        --> Glossitis – inflammation of the tongue, tongue appearing smooth & purplish.
        
        NIACIN
        
        Niacin (nicotinic acid) – a substituted pyridine derivatives.
        
        RDA : male 16 mg/day, female 14 mg/day.
        
        Source : unrefined & enriched grains & cereals, milk, lean meat esp. liver.
        
        Limited quantities can also be obtained from the metabolism of tryptophan
        
        ACTIVE FORM = nicotinamide adenin dinucleotide (NAD+), nicotinamide adenin dinucleotide phosphate (NADP+).
        
        nicotinamide- a derivative of nicotinic acid that contain an amide instead of carboxyl group.
        
        Readily deaminated in the body therefore nutritionally equivalent to nicotinic acid.
        
        CLINICAL
        
        Deficiency of niacin
        
        Causes Pellagra –a disease involving the skin, GI tract& CNS
        
        Symptoms: 3Ds – Dermatitis, Dementia & if untreated Death.
        
        Commonly found in population which the main staple diet is corn (processed corn is low in niacin & tryptophan).
        
        Treatment of hyperlipidemia
        
        PYRIDOXINE
        
        Vitamin B6 is a collective term for derivatives of pyridine -pyridoxine, pyridoxal & pyridoxamine.
        
        Differs only in th the functioning group attached to the ring structure.
        
        pyridoxine- occurs primarily in the plants.
        
        pyridoxal & pyridoxamine – in food obtained from animal.
        
        RDA :male 1.3mg/day, female 1.3 mg/day.
        Source : wheat, corn, egg yolk, liver & muscle meats.
        The requirement for pyridoxine is increased by a high intake of protein.
        
        FX
        
        All 3 compounds are precursors for biologically active coenzymes: pyridoxal phosphate.
        
        pyridoxal phosphate functions as coenzymes for a large number of enzymes particularly those catalyzing reactions involving amino acids.
        [Transamination, deamination, decarboxylation & condensation..]
        
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        FOLIC ACID (FOLATE)
        
        Plays a key role in one carbon metabolism & essential for biosynthesis of purine & pyrimidine (thymine)
        
        RDA: male & female 400 mg/day.
        
        Sources : green leafy vegetables (spinach), whole grain cereals, liver, lima beans, fortified cereals, whole meal bread & orange juice/fruit.
        
        Folic acid is composed of a pteridine ring attached to ρ-aminobenzoic acid (PABA) & conjugated with one or more glutamic acid residues.
        
        Human cannot synthesize PABA or attach the first glutamic acid.
        
        Biologically active form : Tetrahydrofolic acid (THF) by 2 reduction steps of folate by dihydrofolate reductase.
        
        CLINICAL
        
        Folate deficiency: arise when there is increase in demand – pregnancy & lactation or poor absorption due to pathology of small intestine, alcoholism or treatment with drugs..
        
        Primary result – megaloblastic anemia. – caused by diminished synthesis or purine & thymidine leading to inability of cell to produce DNA & to divide. Less RBC.
        
        Alcoholism (inadequate absorption) - administration of commercially prepared folic acid through oral or intramuscular injection.
        
        Folate and neural tube defects in fetus
        
        Early fetal development of neural tube is critically dependent of the presence of folic acid.
        
        Adequate folate nutrition must occur at the time of conception because the critical folate-dependent development occurs in the first few weeks of life.
        
        All woman of child bearing age should consume 0.4mg/day to reduce risk of getting a pregnancy affected by spinus bifida or other neural tube defects.
        
        COBALAMIN (VIT B12)
        
        RDA: male and female 2.4μg/day
        
        Source : synthesized only by microorganisms; not present in plants.
        
        Also present in appreciable amount in liver, whole milk, eggs, oysters, fresh shrimp, pork & chicken.
        
        Structure: Cobalt in the center of corrin ring 2 coenzyme forms; 5’deoxyadenosylcobalamin & methylcobalamin
        
        Storage: liver
        
        FX.
        
        Methyl group carrier. Coenzymes to;
        
        Methylmalonyl CoA mutase (deoxyadenosylcobalamin) – isomerization of methylmalonyl Coa that arises from fatty acids with odd numbers.
        
        Homocysteine methyltransferase (methylcobalamin)- synthesis of methionine. This reaction also releases tetrahydrofolate (THF).
        
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        BIOTIN
        
        RDA : male and female 30 μg/day.
        
        Source : Present in almost all food particularly liver, milk & egg yolk.
        
        Large percentage is supplied by intestinal bacteria.
        
        Function: Coenzyme in carboxylation reactions bound covalently to a lysyl-residue of a biotin-dependent enzyme.
        
        Why? Raw egg white contains avidin, will bind tightly to biotin & prevent from absorption from intestine.
        
        However, with normal diet, it is estimated that 20 eggs per day would be required to induce the deficiency syndrome.
        
        Deficiency : Does not occur naturally (wide distribution in food).
        
        However, addition of raw egg-white to the diet as source of protein will induce symptoms of biotin deficiency – dermatitis, glossitis, loss of appetite & nausea.
        
        PANTOTHENIC ACID
        
        RDA: 5mg/day
        
        Source : widely distributed, mostly in eggs, liver & yeast. Function: component of coenzyme A which functions in the transfer of acyl groups.
        
        Examples: succinyl CoA, fatty acid CoA & acetyl CoA. Also a component of fatty acid synthesis.
        
        Deficiency : rare Not toxic if consume in excess.
    - - Studies nutrients and other substances in food and in the body and how these nutrients relate to health and diseases.
        
        It involves the sources of nutrients and all processes that deal with intake, ingestion, digestion, absorption, transportation, utilization and excretion of food and associated substances.
        
        Personalized genetic constitution which will influenced unique pattern of enzymes which renders him/her more or less susceptible to particular external influences.
      - FOOD: FX
        
        -Energy from carbohydrate, fat and a bit from proteins.
        
        Structural materials required for growth and maintenance of tissues. E.g. proteins and minerals (calcium & phosphorus).
        
        Regulatory substances (Vits & mineral).
        
        Water. Death- 4-5 days without water.
      - REQUIREMENT
        
        RDA
        
        Previously: Recommended daily allowance (RDA) –estimate of the amount of a nutrient required to meet the needs of 98% of healthy individuals in a particular life stage and gender group.
        
        Lowest dietary intake.
        
        FACTOR
        
        Age – RDA varies from infancy to adulthood.
        
        Sex – Dietary allowances for men are approximately 20% greater than woman. Exception- iron
        
        Other factors – 20-30% above normal for pregnant and lactating woman. Patients with injury or illness.
        
        Recommended Nutrient Intakes (RNI)
        
        2005- RNI – Daily intake corresponding to RDA which meets the nutrient requirement of almost all (98%) apparently healthy individuals.
        
        UL – Upper tolerable nutrient intake levels – max intake that is unlikely to pose risk of adverse health effect in the same age and population group.
        
        TYPICAL
        
        Adult male 70kg – 2900 kcal
        
        Adult female 50kg – 2100 kcal.
        [Energy content – calorimeter (kcal/Cal) (calor-heat in Latin).
        Another unit: Joules (J). 1 kcal = 4.128 kJ]
        
        Total energy required = sum of 3 energy-requiring processes that occur in the body.
        
        Basal metabolic rate, BMR
        
        Energy required to carry out the normal body functions (while resting in temperate environment & the digestive system is inactive). E.g. respiration, blood flow and maintenance of neuromuscular integrity. (*stationary car with engine on)
        
        1800kcal for men (70kg)
        
        1300kcal for woman (50kg) = 60%
        
        Thermic effect of food
        
        Production of heat by the body increases as much as 30% above basal level during digestion & absorption of food.
        
        Over 24 hours – 5-10% of total energy expenditure.
        
        Physical activity:
        
        Muscular activity provides greatest variation of energy expenditure.
        
        Amount of energy consumed depends on duration and intensity of exercise.
        
        Sedentary indiv. 30-50%more than BMR
        
        Highly active indiv -100% or more calories.
    - - Body weight: achieve & maintain appropriate body weight.
        
        BMI Total fat: reduce to <30% total calories
        
        Saturated fat: reduce to<10% total calories.
      - Monounsaturated & polyunsaturated fats: increased polyunsaturated to<10% & to 10% monounsaturated.
        
        Complex CHO: 50-60%
        
        Simple CHO: reduce consumption
        
        Fiber: increase dietary fiber to 20-30 g/day.
        
        Cholesterol: <300mg/day Salt: decrease to 3-8g/day