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.
Mannervik
Bengt
B
Department of Biochemistry and Organic Chemistry, Uppsala University, Biomedical Center, Uppsala, Sweden. Bengt.Mannervik@biorg.uu.se
D000818:Animals; D002384:Catalysis; D019143:Evolution, Molecular; D007791:Lactoylglutathione Lyase / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000502:physiology*; D015032:Zinc / Q000502:physiology; D000099301:Hydroxyacylglutathione Hydrolase
D007791:Lactoylglutathione Lyase; D013869:Thiolester Hydrolases; D015032:Zinc; D000099301:Hydroxyacylglutathione Hydrolase