Cystathionine γ-Synthase

Cystathionine γ-synthase is a pyridoxal phosphate enzyme which catalyzes a step in methionine biosynthesis in Salmonella, the formation of cystathionine from cysteine and O-succinylhomoserine. It is the only pyridoxal enzyme known to catalyze this type of reaction, which is called a γ replacement. In addition it can catalyze γ elimination, and β elimination and β replacement, reactions, although these have no known physiological function. The enzyme also catalyzes very rapid exchanges between tritium-labeled water and hydrogens in the α and β positions of a variety of amino acids structurally unrelated to its natural substrates. Studies of the rates of these exchange reactions have now revealed that when the amino acid has an electronegative substituent on carbon 3, exchange is much more rapid in the α than in the β position; in the absence of such a substituent, exchange is slightly more rapid in the β position. NMR studies of exchange reactions in 2H2O have confirmed that exchange is exclusively in the α and β positions, and have shown that all three β hydrogens of alanine are exchanged at the same rate. In α-aminobutyrate and homoserine one of the two sterically distinguishable β hydrogens was exchanged about 100 times faster than the other. The β hydrogens of homoserine were found to be magnetically nonequivalent, and it could be shown that the rapidly exchanging β hydrogen is the one which in solution is more strongly coupled to the α hydrogen. The results have been correlated with previously reported transient changes in the absorption spectrum of the enzyme during the various reactions described.