This detoxification is accomplished by the sequential action of two thiol-dependent enzymes; firstly glyoxalase І, which catalyses the isomerisation of the spontaneously formed hemithioacetal adduct between GSH and 2-oxoaldehydes (such as methylglyoxal) into S-2-hydroxyacylglutathione.[4][5] Secondly, glyoxalase ІІ hydrolyses these thiolesters and in the case of methylglyoxal catabolism, produces D-lactate and GSH from S-D-lactoyl-glutathione.[6]
This system shows many of the typical features of the enzymes that dispose of endogenous toxins. Firstly, in contrast to the amazing substrate range of many of the enzymes involved in xenobiotic metabolism, it shows a narrow substrate specificity. Secondly, intracellular thiols are required as part of its enzymatic mechanism and thirdly, the system acts to recycle reactive metabolites back to a form which may be useful to cellular metabolism.
^ Vander Jagt, D. (1989). The glyoxalase system. In Glutathione: Chemical, Biochemical and Medical Aspects. Part A, D. Dolphin, R. Poulson, and O. Avramovic, eds. (New York: John Wiley & Sons), pp. 597-641.
^ Dixon DP, Cummins L, Cole DJ, Edwards R (1998). "Glutathione-mediated detoxification systems in plants". Curr. Opin. Plant Biol.1 (3): 258–66. doi:10.1016/S1369-5266(98)80114-3. PMID 10066594.
^ Inoue Y, Kimura A (1995). "Methylglyoxal and regulation of its metabolism in microorganisms". Adv. Microb. Physiol.37: 177–227. PMID 8540421.
^ Creighton DJ, Hamilton DS (2001). "Brief history of glyoxalase I and what we have learned about metal ion-dependent, enzyme-catalyzed isomerizations". Arch. Biochem. Biophys.387 (1): 1–10. doi:10.1006/abbi.2000.2253. PMID 11368170.
