Protein (Sources of Protein (Protein Quality
A measure of the extent to…
Distribution in the body:
- 43% Muscle
- 15% Skin
- 16% Blood
- 26% Other
- Not stored for energy requirements
- Have C skeletons that cannot be synthesised from simpler molecules
- Must come from diet
- Histidine, leucine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine
- Not required from diet
- Can be synthesised from other AAs or nitrogenous sources
- Become essential AAs under certain conditions where can't be synthesised in enough quantity
- Tyr usually produced from Phe
- Gln and Arg indispensable after trauma
- Structural: connective tissues, skeletal structures etc.
- Enzymes: All enzymes = proteins.
- Blood transport: Hb, Transferrin, Lipoprotein.
- Peptide hormones: Glucagon, insulin.
- Membrane carriers:GLUT, Na+/K+ATPase.
- Immune function: Antibodies - 4 chains
- Fluid balance: Maintain gradients
- Aliphatic (branched chain)
- Hydroxyl Groups
- Sulfur Groups
- Acidic Groups
- Basic Groups
- Aromatics (ring structure)
- In aqueous solution are ionised
- Most are neutrally charged
- Negatively charged: COO- groups
- Positively charged: additional amino groups
- Depends on the ability of the side chain group to interact with water through H bonds.
- Order of AAs in chain
- Strong covalent bonds between COO and NH. Backbones don't vary, side chains do.
- Local folding into A helices, B sheets or coils
- Weaker H bonds. Stable structure providing strength and rigidity
- Full 3D fold of chain
- Type of interactions determine shape and function, cysteine bonds, EA, clustering of hydrophobic chain.
- Several polypeptide chains together
- Held by H bonds and EA
Digestion and Absorption
- Protein in food broken into individual AA's and join body pool for new protein synthesis
- Mouth: No appreciable digestion
- Stomach: HCl from parietal cells denatures into primary structure. Activates pepsinogen to pepsin. Pepsin hydrolyses peptide bonds and cleaves in poly/tri/dipeptides + free AAs.
- SI: Chyme delivered to duodenum via pyloric sphincter. CCK and Secretin stimulate the release of proenzymes. Free AAs = absorbed at brush border.
- Carrier affinity depends on hydrocarbon mass of side chain and net charge. Branched = more mass.
- Essential = absorbed faster than non essential
- Neutral AAs = absorbed faster than acidic or basic
- Di/tripeptides absorbed faster than AAs.
- 67% of AAs absorbed. Most hydrolysed to generate free intracellular AAs. Many used within intestinal cells for energy or synthesis of new compounds: apoproteins, digestive enzymes, hormones...
- Others are transported across basolateral membrane into portal vein to liver.
Fate of AAs
1.Used to make a dispensable AA
2. Oxidised for energy
3. Used to make a new protein
4. Used to make other compounds (N-containing, non-protein compounds, purine bases etc
Formation of Dispensable AA:Transamination
Alanine synthesis from Glucose:
- Keto Acid A + Amino Acid B → Amino Acid A + Keto Acid B
- Pyruvate = Keto Acid (AA transfers from aspartate to make alanine plus oxaloacetate.
- Oxaloacetate = New Keto Acid
- Way to shuttle glucose around the body
- Pyruvate + Aspartate = Oxaloacetate + Alanine
- C skeleton can enter CAC
Oxidisation to Energy
- AA → NH3 + C Skeleton (a keto acid) → Energy + CO2
- AA + AA → Dipeptide + Water (released when bonding together)
- Dehydrogenase + Water
- Makes Keto acid + NH4
- Amino group = Makes ammonia, joins with CO2 to make urea (non-toxic)
- C Skeleton fed into pyruvate or ACoA
Sources of Protein
- Bread 11%
- Poultry + Milk 9%
- Beef and Veal 8%
- Social/cultural environment
- Personal philosophy
- A measure of the extent to which a protein provide enough indispensable AAs for growth, maintenance and repair.
- Influenced by composition and digestibility
- Insufficient in one or more.
- Proteins low in different AAs so when eaten together are complete e.g. wheat (lysin) and chickpeas (sulfur)
- Animal sources: typically 90-99% digestible
- Plant proteins: typically 10-90%
Alternates: AA score (compared to reference protein) or Protein efficiency ratio (gain in body weight per gram of protein).
- mg most limiting AA / mg of same AA in scoring pattern x true digestibility
Current Indicator AA Oxidation Method
- One AA is inadequate protein synthesis is impaired resulting in increased oxidation of all AAs.
- 13C labelled indicator AAs given IV to measure oxidation of indicator AA
- Expensive and time consuming
- Composition of breast milk
- Factorial method adds together estimated obligatory nitrogen loss from urine, faeces and sweat
- Nitrogen balance method
Nitrogen Balance Method
- Protein = 16% N
- Measure fluxes in N as measure of protein balance
- Intake compared with amount in urine, faeces, skin
- Nitrogen balance: Needs met
- Negative balance: Inadequate
- Positive: Growth e.g. children, pregnant women etc
- Difficult to accurately measure intake and losses
- Daily variation in N excretion so multi day studies needed
- Expensive and time consuming
- Doesn't provide info on protein metabolism and if protein intakes are optimal
- 0.60g/kg body weight WOMEN
- 0.68g/kg body weight MEN
- Age and growth
- Pregnancy and lactation (add 12-17g/day)
- Physiological stress
- Energy intake
- Performance in sports
Negative Balance - Short Term
- Proteins in liver and kidney
- THEN skeletal muscle
- Female: 37g/d
- Male: 52g/d
- AMDR = 15-25% of energy
- Values increase with increasing age
- Elderly Female: 46g/d
- Elderly Male: 65g/d
- 15 year old males and females are generally eating within the AMDR for protein.
Inconsistently assoc. with:
- Kidney stones
- Max rate of urea synthesis = 40% energy from protein.
- Excess theoretically excreted in urine
- Increased protein intake stimulates muscle synthesis esp directly after exercise.
Two Compartment Model
- Body Cell Mass
- Somatic (Muscle) + Visceral (WBCs, Serum, RBCs, Liver, Gut)
Group of inherited disorders of PHE metabolism, characterised by impaired PAH activity
- If not treated by 3 weeks → irreversible mental retardation
- Symptoms apparent 3-6months
- Guthrie bacterial inhibition heelprick test, PHE greater than 120umol/L
- Developmental delay, behavioural abnormalities, motor deficits, seizures, eczema, mousy odour, fair colouring
- Phenylalanine hydroxylase can't convert enough PHE to TYR, TYR becomes conditionally dependent
- Cause = PHE enzyme or Biopterrin?? Different treatments
- More than 450 mutations known
- Autosomal R
- Cause: Accumulation of PHE or PHE by-products OR decency of TYR or TYR products
PKU Diet Therapy
- Maintain blood PHE
- Principle: restrict PHE intake and supplement TYR intake**
- Support normal growth + development in children
- Prevent behavioural abnormalities in children
- Improve psychological function in untreated adults
- Prevent neurologic deterioration in adults
- ALL proteins contain PHE, formula is centre of diet
- Low/no PHE formula
- PHE = natural sources
- Rest = PHE free diet
- AVOID aspartame (synthetic PHE containing sweetener)
- Lower intelligence reversible if diet resumed
- Holtzman et al: diet discontinuation in children detrimental for IQ level
- 1 person = $70-80,000
- Annually in NZ $5,000,000
- Subsidised up until 16
- Normal health, development, lifespan, IQ relatively normal
- ONLY if remain on diet