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.
Department of Biochemistry and Organic Chemistry, Uppsala University, Biomedical Center, Uppsala, Sweden. Bengt.Mannervik@biorg.uu.se
Bengt
B
Mannervik
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