Stereochemistry of <i>si</i>‐Citrate Synthase and ATP‐Citrate‐Lyase Reactions

Abstract

A new synthesis of R ‐ and S ‐acetic acid ( R ‐ and S ‐[ 2 H 1 , 3 H 1 ]acetate) is described. R ‐Acetic acid after conversion into citrate on si ‐citrate synthase and cleavage of the citrate with citrate lyase regenerates an acetate which is still predominantly R. S ‐Acetic acid when put through the same sequence yields acetic acid which is predominantly S. Essentially the same results as in (2) and (3) are obtained when ATP‐citrate lyase is substituted for citrate lyase. The conclusion is drawn that on si ‐citrate synthase, the replacement of hydrogen by oxaloacetic acid proceeds with inversion of configuration at the methyl group. It also follows that ATP‐citrate lyase, like citrate lyase, cleaves citrate with inversion of configuration. It is further deduced that there is a normal intramolecular deuterium‐isotope effect, with respect to the chiral‐methyl group, in the condensation of chiral acetate with oxaloacetate on si ‐citrate synthase.