THE MECHANISM OF ACTION OF GLYOXALASE

Abstract

The conversion of methylglyoxal to lactic acid in animal tissues was discovered by Neuberg (1) and Dakin and Dudley (2). The enzyme responsible for the reaction was named glyoxalase (3). Subsequently the enzyme was found to be widely distributed in animal tissues, plants, and microorganisms. Lohmann (4) demonstrated that reduced glutathione was required for the action of glyoxalase. Jowett and Quastel (5) proposed the formation of an addition complex between methylglyoxal and glutathione as an intermediate to lactic acid formation. Yamazoye (6) was first to show the formation of an intermediate in crude liver extracts which was distinct from the chemical addition complex between methylglyoxal and glutathione. Hopkins and Morgan (7) demonstrated the existence of a protein factor which accelerated lactic acid formation from methylglyoxal in the presence of partially purified glyoxalase. The factor itself had no apparent effect on the reaction when tested in the absence of glyoxalase. Preliminary reports on the existence of two separable enzymatic steps in the conversion of methylglyoxal to lactic acid have been published recently (8, 9). The first step consists in a condensation reaction between methylglyoxal and glutathione catalyzed by an enzyme referred to in this paper as glyoxalase I. This condensation product, in a second step which is catalyzed by glyoxalase II, is then broken down into glutathione and lactic acid. It is the purpose of this paper to describe these two reactions and the enzymes which catalyze them.