Synthesis of Homocysteinesulfinic Acid, Homocysteinesulfonic Acid and Homocysteinesulfonamide,and Reactivities with Various Enzymes Acting on Glutamic Acid and Glutamine

Abstract

We synthesized L-homocysteinesufinic acid and L-homocysteinesulfonic acid, analogs of L-glutamic acid from L-methionine with overall yield of 18 and 30%, respectively. L-Homocysteinesulfonamide was synthesized as an analog of glutamine with an overall yield of 3%. Their reactivities with various enzymes acting on glutamic acid and glutamine were examined. L-Homocysteinesulfinic acid reacted with glutamate dehydrogenase (K_m=13.3 mM, V_max=2.46 U/mg), glutamate decarboxylase (K_m=38.4 mM, V_max=2.39 U/mg) and glutamate oxidase (K_m=2.42 mM, V_max=22.8 U/mg). It competitively inhibited glutamate decarboxylase (K_i=6.23 mM). L-Homocysteinesulfonic acid did not react with all the enzymes tested, but searved as a competitive inhibitor of glutamate decarboxylase (K_i=1.24 mM). L-Homocysteinesulfonamide competitively inhibited glutaminase (K_i=4.27 mM) and asparginase (K_i=27.2 mM).