Transcript Prof. Kamakaka`s Lecture 12 Notes

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
Hydroxylation
Oxidation
Step6-8
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
Citric acid cycle and Anabolism
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
The cycle and Anabolism
Regulatory steps
Regulation
Glyoxylate cycle
Glyoxylate and Citric acid cycle