The Citric Acid cycle

Pyruvate to Acetyl CoA

Pyruvate and acetyl-CoA used for energy AND to synthesize amino acids and lipids etc

Mitochondria

Pyruvate in cytoplasm Enters mitochondria Pyruvate dehydrogenase is in matrix

Pyruvate Dehydrogenase

Huge complex (50nm) (ribosome is 5nm) Three sub-complexes- E1, E2 and E3 Commits pyruvate to AcCoA formation

Pyruvate dehydrogenase

Pyruvate to Acetyl CoA

The reaction

Ist step intermediate

2nd step intermediate

3rd step intermediate

4th step

Reactions in the complex

Co-ordinated substrate channeling-pass substrate form 1 active site to next Fast reaction, minimized side reaction, co-ordinated process, high substrate conc

Oxidative decarboxylation of pyruvate

Regulation of PDH

Increased AcCoA inhibits E2 in PDH (monitors amt of energy). High AcCoA, switch off respiration, use pyruvate to switch on gluconeogenesis (formation of glycogen etc)

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Citric Acid cycle

2C + 4C -------> 6C -----> CO2 + 4C

16 electrons

The overall reaction

Step1

Oxaloacetate and acetylCoA bind enzyme in open state. Enzyme changes shape, brings the reactants together and condensation occurs

Step2

Step3

Step4

Step5

Cleavage of thiol energy bond and release of CoA is coupled to formation of GTP PO4 nucleophilic attack on succinate His cleaves PO4 off of succinate. PO4 transfers from His(enzyme) to GDP forming GTP

Details

Cleavage of thiol energy bond and release of CoA is coupled to formation of GTP PO4 nucleophilic attack on succinyl CoA releasing CoA. His cleaves PO4 off of succinate. PO4 transfers from His(enzyme) to GDP forming GTP

Step6-8

Oxidation Hydroxylation

Step6

Succinate dehydrogenase- uses FAD and generates FADH2. This enzyme is not in matrix but in inner mitochondrial membrane and hands FADH2 directly to the electron transport system

Step7

Step8

Role of the citric acid cycle in anabolism. Intermediates of the citric acid cycle are drawn off as precursors in many biosynthetic pathways. Shown in red are four anaplerotic reactions that replenish depleted cycle intermediates

Citric acid cycle and Anabolism

The cycle and Anabolism

Regulatory steps

Regulation

Glyoxylate cycle

Glyoxylate and Citric acid cycle