When the citric acid cycle was first proposed by Krebs, the “problem” was not that a chiral molecule was produced from a non-chiral molecule—this is easily understood. The difficulty was in understanding why formation of the double bond of cis-aconitate, and subsequent addition of water to form isocitrate, occurred only in the moiety contributed originally by oxaloacetate and not in the group derived from acetyl CoA. When isotopically labeled acetate was added to cells the 14 C-labeled carbon atoms appeared in citrate. Since citrate is a symmetric molecule, the labeled carbon atoms were expected to show up equally in the two versions of isocitrate by arrows 1 and 2. Instead, only the left-hand form was produced. This mystery was later solved and find out the reason why only form form is produced?
The degradation of both odd-chain fatty acids and
cholesterol produces propionyl coenzyme A (propionyl-
CoA) (5–9) which must be further metabolized as accumu-
lation of propionyl-CoA leads to the toxicity to the bacilli