Question

Is citrate treated as the symmetric molecule it is, or treated asymmetrically in the citric acid cycle? Explain your reasoning, and discuss why this is an interesting and important question in biochemistry and cell biology.

Answer 1

Citrate is a symmetric molecule without any chiral center or asymmetric carbon because its two terminal carboxyl groups are indistinguishable. Being symmetric, it can be assumed that citrate molecules will yield – a) ketoglutarate labeled in the α-carboxyl group and b) a-ketoglutarate labeled in the y-carboxyl group. But this does not happen because the α-ketoglutarate obtained from the suspension has molecules labeled only in the γ-carboxyl group. Therefore, symmetric molecule cannot act as an intermediate in the pathway from acetate to α-ketoglutarate. This make it necessary to first extract asymmetric tricarboxylic acid such as cis-aconitate or isocitrate from acetate and oxaloacetate.

As per Alexander Ogston, Citrate without chiral center can react asymmetrically when the enzyme acting upon it has an active site that is asymmetric.