The roles of ATP in living cells and the mechanisms of production 2 Flashcards
The fate of pyruvate
Under aerobic conditions, oxidation and complete degradation
In the mitochondria
Glycolysis occurs in the cytosol
Pyruvate is transported into the mitochondria
Transport of pyruvate into the mitochondria
In aerobic conditions, occurs via specific carrier protein embedded in the mitochondrial membrane
Pyruvate undergoes oxidative decarboxylation by the pyruvate dehydrogenase complex to form acetyl coa
Reaction is irreversible and is the link between glycolysis and the citric acid cycle
The pyruvate dehydrogenase complex
Three different enzymes
Five different coenzymes
Four different vitamins are vital to this complex in humans
- thiamine (in TPP)
- riboflavin (in FAD)
- niacin (in NAD)
- pantothenate (in CoA)
Tricarboxylic acid cycle
Also known citric acid krebs cycle
Final common pathway for the oxidation of fuel molecule
In 8 steps, acetyl residues (CH3-CO-) are oxidised to CO2
Reducing equivalents transferred to NAD+ or ubiquinone and from there to the respiratory chain
The TCA cycle: an overview
A 4-carbon unit condenses with a 2 carbon unit
Eventually, 2 carbons leave the cycle as CO2 and the 4C unit is regenerated
4 oxidation reduction reactions and one molecule of ATP is produced directly for each round of the cycle
8 intermediates of the TCA cycle
Acetyl CoA Citrate Isocitrate Alpha ketoglutarate Succinyl CoA Succinate Fumarate Malate Oxaloacetate
The 9 enzymatic steps in the cycle
Condensation- citrate synthase
Dehydration- aconitase
Hydration- aconitase
Oxidative decarboxylation- isocitrate dehydrogenase
Oxidative decarboxylation- alpha ketoglutarate dehydrogenase
Substrate level phosphorylation- succinyl CoA synthetase
Dehydrogenation- succinate dehydrogenase
Hydration- fumarase
Dehydrogenation- malate dehydrognase
Regulation of the TCA cycle
Flow of carbon atoms from pyruvate into and through the TCA cycle is tightly regulated at 2 levels:
- Conversion of pyruvate to acetyl-CoA (PDH reaction)
- Entry of acetyl-CoA into the TCA cycle
Also regulated at isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase reactions
Other compounds that feed into the TCA cycle
Fatty acids and some amino acids can be a source of acetyl-CoA
Products of the TCA cycle
Energy released from oxidations is conserved in the reduction of:
- 3 NADH
- 1 FADH2
- 1 GTP (ATP)
- 2 CO2 also produced
Transport of NADH electrons
Two shuttles:
- The glycerol-3-phosphate shuttle, especially prevalent in brain and muscle
- The malate-aspartate shuttle, in liver and heart
Both shuttles act to regenerate NAD+ and make 1.5 or 2.5 moles of ATP
The glycerol-3-phosphate shuttle
In brain and muscle
- NADH reduces dihydroxyacetone to glycerol-3-phosphate
- catalysed by G-3-P dehydrogenase
- G-3-P diffuses into the intramembrane space
- mitochondrial G-3-P dehydrogenase uses FAD to oxidise it to DHAP
- FADH2 carries electrons to ubiquinone in the electron transport chain eventually producing 1.5 ATP
The malate- aspartate shuttle
In liver and heart
- electrons of cytosolic oxaloacetate yielding malate
- malate is transported into the matrix via an exchanger protein that transports alpha KG in the opposite direction
- in the matrix, malate is oxidised back to oxaloacetate
- NADH formed transfers its reducing power to the electron transport chain producing 2.5 ATP
- oxaloacetate is converted to aspartate
- aspartate is transported to the cytosol via exchanger protein that transports glutamate into the matrix
- cytosolic aspartate is trnasaminated to oxaloacetate
The electron transport chain
Comprises four large multi- unit proteins intrinsic to the inner mitochondrial membrane
Catalyse a series of reactions:
NADH + H+ + 1/2 O2= NAD+ + H2O
Energy released from this reaction not released as heat but tightly coupled to the production of ATP
Components of electrons transport chain
Complex I
Complex II
Complex III
Complex IV