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Cells & Energy Production (Cellular respiration Production of…
Cells & Energy Production
Energy
Enthalpy = Heat content of molecules
-∆H = exothermic - gives out heat
+∆H = endothermic - takes in heat
Enthropy = Degree of randomness (∆S)
Catabolism
Degradation of complex substances into smaller simpler ones
Liberates free energy to drive synthesis of ATP from ADP + Pi to enable energy process via oxidation of energy from food
Anabolism
Synthesis of complex organic substances from smaller simpler ones
ATP
Each cell contains small amount of ATP and lasts for short periods of time
The cell cannot get ATP extracellularly as ATP, ADP or AMP as they cannot diffuse through the cell membrane
Each cell must synthesise ATP and rapidly turns over in the cell by breakdown of ADP + Pi and resynthesizing to ATP
ATP enables:
Chemical work
Muscle contraction
Cell signalling
Ion pumping
Pumping molecules against concentration gradient
Cellular respiration
Production of ~38mol ATP per 1mol glucose
3 main processes:
Glycolysis
Substrate level phosphorylation in cytosol
Citric acid cycle
Substrate level phosphorylation in mitochondria
Electric transport chain
Oxidative phosphorylation in mitochondria
Glycolysis
Conversion of glucose (hexoses) into pyruvate
Key metabolic pathway to supply ATP, reducing equivalents (NADH) and converts carbohydrates into compounds which undergo terminal oxidation (acetyl-CoA) or are used for biosynthesis
When the reactions reverse, glucose in synthesised from non-carbohydrate sources
(gluconeogenesis)
Major purpose of gluconeogenesis is to keep up sufficient oxygen supply to brain and muscles
Glucose is transported across cell membrane and comes to equilibrium
Glycolosis
Each 6 carbon glucose molecule broken down into 2x 3 carbon molecules
Dephosphorylation yields 4mol ATP but phosphorylation utilises 2 ATP = 2 ATP net gain
2mol NADH produced and can be used in oxidative phosphorylation
Glucose --> glucose-6-phosphate --> fructose-6-phosphate --> fructose-1-6-biphosphate --> 2 x 3 carbon sugar molecules per glucose i.e pyruvate
Pyruvate --> phosphoenolpyruvate --> 2-phosphoglycerate --> 3-phosphoglycerate --> 1,3-biphosphoglycerate
Pentose phosphate cycle
Pathway is parallel to glycolysis
Anabolic rather than catabolic
Glucose-6-phosphate dehydrogenase is the rate controlling enzyme of this pathway
Especially important in erythrocytes
Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is an inborn error of metabolism that predisposes to haemolysis (destruction of red blood cells) - Can be triggered by eating broad (fava) beans
Can occur without oxygen
Happens in the cytoplasm
When one molecule of glucose undergoes glycolysis, the net production is 2 ATP, 2 NADH & 2 pyruvate
Pyruvate is a 3-carbon molecule
Pyruvate
2mol pyruvate formed from 1mol glucose
2mol NADH produced equivalent to 5mol ATP/1mol glucose
Pyruvate metabolised in 4 ways:
Reduction to lactase
Substrate of gluconeogenesis
Oxidation to acetyl co-enzyme A and:
-used in fatty acid synthesis
-Or completely oxidised to CO2 and water
Decarboxylation and oxidation of pyruvate to form acetyl co-enzyme A require the co-enzyme thiamin diphosphate. Thiamin deficiency impairs the process
Acetyl co-enzyme A
Final fate of pyruvate from glycolysis is complete oxidation to CO2 and water
Acetyl co-enzyme A is the entry point into the citric acid cycle
Acetyl-CoA is formed from pyruvate in a complex set of reactions catalysed by pyruvate dehydrogenase (PDH)
The conversion involves decarboxylation and oxidation steps that are similar to subsequent reactions that occur within the citric acid cycle itself
Citric acid cycle/Krebs cycle
Set of 8 reactions - key to metabolism
Main purpose = extract electrons from carbon compounds in a sequence of oxidation-reduction reactions
Electrons will be used to generate a large amount of energy through oxidative phosphorylation
Front end of aerobic respiration
Acetyl-CoA & citric acid cycle
For each oxidised mol of acetyl-CoA in citric acid cycle:
3mol NAD+ reduced to NADH ~7.5 mol ATP
1 flavoprotein reduced ~1.5mol ATP
1mol ADP phosphorylated to ATP
10mol ATP
TOTAL
produced from oxidation of 1mol acetyl-CoA
But 2mol acetyl-CoA produced from 1mol of glucose, so 20mol ATP produced from each oxidised mol of glucose
After acetyl-CoA is produced, it has two possible destinations:
Oxidation to CO2 in citric acid cycle
Lipid synthesis
Oxaloacetate - 4-carbon compound reacts with acetyl-CoA to form 6-carbon compound
Cycle continues as series of reactions to loose 2 carbon atoms as CO2 at each stage, oxidation steps enable to reformation of oxaloacetate
Oxaloacetate is the precursor for gluconeogenesis but fatty acids cannot be used
Substrate-level phosphorylation
ATP generated from glycolysis and citric acid cycle
Small amount
Glycolysis yields net gain of 2mol ATP anaerobically
Citric acid cycle yields net gain of 2mol ATP aerobically
Oxidative phosphorylation
Oxidation of NADH to NAD+ yields 2.5mol ATP
Oxidation of FADH2 to FAD yields 1.5mol ATP
Electron transport chain yields 32-34mol ATP
Amount differs depending on which electron carrier (NADH or FADH2) is used
NAD+ & NADH
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in all living cells
NAD+ exists in two forms and reduced to NADH
Involved in redox reactions, carrying electrons from one reaction to another
NAD+ is an oxidising agent accepting electrons from other molecules and becomes reduced. The reaction forms NADH, which can then be used as a reducing agent to donate electrons
FAD, FADH, FADH2
Flavin adenine dinucleotide (FAD) is a redox enzyme cofactor involved in several important enzymatic reactions in metabolism
Flavoproteins contain a nucleic acid derivative of riboflavin
Mitochondria structure
ATP synthase enzyme and the electric transport chain are embedded in the inner membrane
Cristae
Inter-membrane space
Matrix
Inner membrane
Outer membrane
Electron transport chain
Chain of enzymes located on the inner mitochondrial membrane
Main source on energy on aerobic pathway
Inner mitochondrial membrane contains 4 sets of enzymes complexes named 1-4
NADH & FADH2 electrons from the krebs cycle is used in ETC
Electrons travel from complex 1 to complex 4, generating energy from pumping ions into the inner membrane space from the matrix of the mitochondria
The continuous pumping causes a higher concentration of hydrogen ions in the inter-membrane space compared to the matrix of the mitochondria
This generates a positive charge in the inter-membrane space and a negative charge in the matrix of the mitochondria (electrochemical gradient)
ATP synthase transports hydrogen ions into the matrix of the mitochondria and uses the energy
Free radicals & oxidative stress
Reactive oxygen species (ROS)
Highly reactive molecular species with unpaired electron
Any reaction involving a radical generates another radical unless the two react together
Free radical reactions are chain reactions
Oxidative stress - a disturbance in the prooxidant-antioxidant balance in favour of the former leading to potential damage = oxidative damage
Oxidative damage is associated with disease and tissue damage
Oxidative damage
Strands break in DNA/modification of bases
May cause heritable mutations (in germ cells)
May induce cancer (in somatic cells)
Oxidation of poly-unsaturated fatty acids in lipids
Lipid peroxides are involved in atherogenesis
Lipid peroxides break down to dialdehydes which modify proteins and nucleic acid bases
Oxidation of amino acids in proteins
May lead to formation of antibodies against modified protein
Oxidised amino acids may catalyse further formation of oxygen radicals
Free radicals induced by
Corporeal factors
Aerobic metabolism
Obesity
Diabetes
Exercise
Injury
Immune response
Metabolism
Environmental factors
Air pollution
Asbestos
Radioactive emissions
Tobacco smoke
UV radiation
Trace elements - iron & copper
Defences to free radicals
Enzymatic
Superoxide dismutase
Catalase
Glutathione peroxidase
Protein binding of metal ions
Iron bound by transferrin, haemosidierin, ferritin
Copper bound by caeruloplasmin
Metal ions bound by metallothionein
Diet-derived antioxidants
a-tocopherol
Ascorbic acid
Polyphenolics - flavanoids, flavanones, anthocyanins, resveratrol, catechins
Carotenoids - B-carotene, lycopene, zeaxanthin, capsanthin, lutein
Some antioxidants may be pro-oxidants
b-carotene may be an antioxidant at low partial pressure of oxygen but a pro-oxidant at high partial pressure
Iron
Vitamin C
Vitamin E
Fenton reaction
A catalytic process that converts hydrogen peroxide, a product of mitochondrial oxidative respiration, into a highly toxic hydroxyl free radical
Reaction of transition metals with oxygen radicals
Metabolically important metal ions:
Iron
Copper
Manganese
Cobalt
Nickle
Zinc
Cerium
Chromium