TCA Cycle: Stage 1 Flashcards
What does the cycle do?
ALSO KNOWN AS CITRIC ACID CYCLE AND KREBS CYCLE
TCA= Tricarboxylic Acid Cycle
Overall: Cycle oxidises pyruvate (formed during glycolysis) —-> CO2 + H2O , with concomitant production of energy (ATP during oxidative phosphorylation), but it produces reduced cofactors= NOT ATP during TCA
Cycle also has role in producing precursors for biosynthetic pathway
Where does the glycolysis occur? (Stage 1, carbohydrate catabolism)
Cytoplasm (cytosol) of all cells
Formation of complexes of glycolytic enzymes
Complexes= Allow local concentrations of intermediates to differ from bulk cellular concentrations
Where does stage 2 and 3 of energy generation process occur? (TCCA)
Cytoplasmic compartment of aerobic prokaryotes
Eukaryotic: Mitochondria
Mitochondria: Contain a double membrane system= Import of metabolites in cellular compartment via transport systems is needed
Matrix of mitochondria: Citric acid cycle and pyruvate oxidation
How efficient is the TCA cycle at generating ATP?
Glycolysis= Only produce 2 molecules of ATP + 2x NADH
TCA= Produce reduced cofactors (NADH, FADH2)= Oxidation of the cofactors produce 30 molecules of ATP per molecule of glucose
Aerobic respiration is much more efficient at producing ATP than anaerobic respiration
What happens during the first step of the TCA cycle? (Oxidative decarboxylation)
1) Oxidation of fuel molecules to acetyl coA
Pyruvate is oxidised to Acetyl CoA as coenzyme A carrier molecule removes the acetyl group from the pyruvate= Acetyl CoA= Forms thioester group which is highly reactive
Pyruvate is also oxidised by pyruvate dehydrogenase= Using NAD+ to produce NADH
Also loses one carbon atom= CO2
OVERALL: Pyruvate + CoA + NAD+ —-> Acetyl CoA + CO2 + NADH + H+
Acetyl CoA is ALSO produced by oxidation of fats= Processes of lipid catabolism and carbohydrate catabolism are linked here= Keeps cycle moving
1) Decarboxylation
2) Oxidation
3) Transfer to CoA= Acetyl CoA
What is the structure and function of pyruvate dehydrogenase?
Contains 3 different enzymes, and 5 coenzymes (3 cofactors, 2 substrates)
3 enzymes are:
1) Pyruvate dehydrogenase component= TPP= Oxidative decarboxylation of pyruvate
2) Dihydrolipoyl transacetylase= Lipoamide= Transfer of acetyl group to CoA
3) Dihydrolipoyl dehydrogenase= FAD= Regeneration of the oxidised form of lipoamide= Also makes acetyl coA
How is step 1 carried out by pyruvate dehydrogenase?
1) TPP: Reactive carbon atom from=2-carbon unit from pyruvate is attached
2) Lipoic acid: Reactive disulphide= Loses Acetyl group, pyruvate attached to enzyme via amide linkage to lysine side chain
3) FAD: Redox reactions at the reactive sites
2-carbon unit from pyruvate attached through mobile link (via lipoamide) = can move to different sites in enzyme complex
Complete reaction cycle occurs within complex= Increases overall reaction rate as no diffusion is necessary + Minimises side reactions as reactive intermediates are protected
Essentially irreversible
How is the pyruvate dehydrogenase complex regulated?
Regulated: Reversible phosphorylation
Phosphorylation is promoted by high levels of ATP= feedback inhibition of pyruvate dehydrogenase by energy change
-Also inhibited by high levels of pyruvate= Substrate activation of pyruvate dehydrogenase
-Products: Also cause feedback inhibition= Spares glucose when fatty acid degradation is active
BASICALLY: High levels of stuff= Regulation of pyruvate dehydrogenase
What is the disorder caused by shortage of Vitamin B1? How doe this link with pyruvate dehydrogenase?
Beriberi= Neurologica and cardiac symptoms
-Thiamine= Needed for production of TTP
-Nervous tissues rely on glucose, rather than fats as fuel
=No Vitamin B (Thiamine)= No pyruvate dehydrogenase= = Increasing levels of pyruvate build up= Nervous system damaged as not enough ATP is generated for anabolic metabolism
What is the other source of Acetyl CoA?
Catabolism of fatty acids
- They are derived from dietary lipids by hydrolysis
- Major source of energy for humans= More ATP is generated from fats than sugars
- Consist mostly of trigacylglycerol fats= Broken down= Glycerol can be fed into glycolysis
How does fatty acid oxidation work?
Fatty acid catabolism to generate Acetyl CoA in mitochondria and peroxisomes:
Oxidation process for fatty acids is initiated by formation of a Coenzyme A
1) Fatty acid + ATP Acyl adenylate + Ppi
Reaction is catalysed by acyl CoA synthetase
2) Acyl adenylate + HS-COA Acyl CoA + AMP
Essentially the same processes in both mitochondria or peroxisomes
Basically: Fatty acid breakdown brings about the oxidation of long chained fatty acids
1) fatty acids converted into acyl coenzyme A (CoA) derivatives
2) Degraded by successive removal of 2-carbon units from the end of the fatty acid= Acetyl CoA
3) Pathway produces FADH2, NADH directly
Acetyl CoA can then enter the citric aid cycle
