Cystathionine γ-Synthase from Salmonella: β Elimination and Replacement Reactions and Inhibition by O-Succinylserine

Abstract

Abstract Cystathionine γ-synthase is a pyridoxal-P enzyme which catalyzes replacement of the succinyl group of O-succinyl-homoserine by cysteine. In the absence of cysteine, succinate is rapidly eliminated to form α-ketobutyrate. O-Succinylserine has been synthesized. The succinyl group underwent a slow replacement by homocysteine to yield cystathionine and a rapid elimination, in the absence of a mercaptoamino acid, to yield pyruvate. Thus the enzyme can catalyze the whole spectrum of elimination and replacement reactions of β- and γ-substituted amino acids. While catalyzing pyruvate formation from succinylserine, the enzyme became partially inhibited. The inhibition is similar to that of threonine dehydrase by serine, but it is more rapidly reversible and responds differently to changes in pH. A modified procedure has also been described for preparing pure cystathionine γ-synthase from Salmonella.