Citric Acid Cycle Flashcards
Citric Acid Cycle role
Catalyze the net oxidation of acetyl-CoA to CO2
Amphibolic
Both catabolism and anabolism
Pyruvate dehydrogenase complex
Multienzyme that links glycolysis to the CAC
What are the advantages of a multienzyme?
-Intermediates are never released into solution because the product of one active site quickly moves to the next
-Easier to regulate all enzymes
-Minimizes side rxns
What are the 3 active sites?
E1(steps 1,2), E2 (step 3) and E3 (steps 4,5)
Where is the Pyruvate dehydrogenase complex located?
The mitochondrial matrix (pyruvate from glycolysis must move from the cytosol to the mitochondrion
E 1 (steps 1,2)
Decarboxylation of pyruvate and transfer of the acetyl group to lipoamine
E2 step 3
Transfer of the acetyl group to CoA
E3 (step 4,5)
Dihydrolipoamide os reoxidized using NAD+ and FAD
Lipoamide linkage
Linked to a long flexible chain of lysine in the E2 active site
How does Acetly-CoA enter the CAC
Acetyl-CoA enters from the pyruvate dehydrogenase complex, amino acid catabolism or fatty acid oxidation
What steps of the CAC are irreversible?
1,3,4
Where does step 6 occur vs all the other steps
Step 6 occurs in the inner membrane and the rest occur in the mitochondrial matrix
Result of each acetyl entered
2 molecules of fully oxidized CO2 are produced
Step 1 Citrate synthase
Formation of citrate; 4c to 6c; large negative free energy= -31.5
Why is the CAC cyclic?
The large negative delta G from 1. Citrate synthase can pull the 8. malate dehydrogenase reaction forward as it has a positive delta G
Step 2 Aconitase
Hydroxyl is moved to the carbon originating from step 8. Oxaloacetate and not from the carbon from acetyl CoA
Where are the electrons going in step 6
Electrons are passed to the FAD enzyme prosthetic cofactor to form FADH2; FADH2 then passes 2 e- to Q producing QH2
Energy yield from the aerobic breakdown of glucose to CO2
6-NADH —> 15 ATP
2 QH ——> 3 ATP
2 GTP
4 CO2
How is the kreb cycle regulated
At the irreversible steps (1,3,4)
How does step 1 regulate
Substrate availability of Acetyl CoA and oxaloacetate;
Product and feedback Inhibition by NADH, citrate and succinyl-CoA
How does step 1 regulate
Substrate availability of Acetyl CoA and oxaloacetate;
Product and feedback Inhibition by NADH, citrate and succinyl-CoA
How does step 3 regulate
Allosteric Inhibition by NADH and ATP; allosteric activated by Ca2+ and ADP
How’s does step 4 regulate
Allosterically Inhibited by succinyl-CoA and NADH
Allosterically Activated by Ca2+