Molecular enzymology of the glyoxalase system

The glyoxalase system catalyzes the conversion of 2-oxoaldehydes into the corresponding 2-hydroxyacids. This biotransformation involves two separate enzymes, glyoxalase I and glyoxalase II, which bring about two consecutive reactions involving the thiol-containing tripeptide glutathione as a cofactor. The physiologically most important substrate methylglyoxal is converted by glyoxalase I into S-D-lactoyl-glutathione in the first reaction. Subsequently, glyoxalase II catalyzes the hydrolysis of this thiolester into D-lactic acid and free glutathione. The structures of both enzymes have been obtained via molecular cloning, heterologous expression, and X-ray diffraction analysis. Glyoxalase I and glyoxalase II are metalloenzymes and zinc plays an essential role in their diverse catalytic mechanisms. Both enzymes appear linked to a variety of pathological conditions, but further investigations are required to clarify the different physiological aspects of the glyoxalase system.