Question

Original experimental deciphering of CAC used 13C-labeled acetyl-CoA. So where does each carbon go in the citrate molecule and can you explain why the labeled acetyl carbons come off as CO2 in the second cycle of CAC if the label is on the carbonyl, and in later rounds if the label is in the methyl group?

Answer 1

Acetyl group in any organic compound is the most easily oxidisable group to Carbon dioxide. The same is true for citrate in citric acid cycle (CAC). Since CAC is a cycle, the citrate is regenerated at the end of the cycle by combination with the end product of glycolysis (pyruvate). The carbons other than acetyl groups and one of the acetyl group carbons do not essentially undergo a change in their positions but are a part of rearrangement enzymatic reactions.

Precisely this is the reason that labelled carbons on methyl groups are released in later rounds during the CAC and acetyl carbons during its first few steps.

Note: This answer is based on reductionist approach to the above problem. For more detail, the CAC with all it's enzymatic steps can be studied.