Glyoxalase system

The glyoxalase system is a set of enzymes that carry out the detoxification of methylglyoxal and the other reactive aldehydes that are produced as a normal part of metabolism.[1][2] This system has been studied in both bacteria and eukaryotes.[2][3][4] This detoxification is accomplished by the sequential action of two thiol-dependent enzymes; firstly glyoxalase І, which catalyzes the isomerization of the spontaneously formed hemithioacetal adduct between glutathione and 2-oxoaldehydes (such as methylglyoxal) into S-2-hydroxyacylglutathione.[5][6] Secondly, glyoxalase ІІ hydrolyses these thiolesters and in the case of methylglyoxal catabolism, produces D-lactate and GSH from S-D-lactoyl-glutathione.[7]

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.[3] 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.

  1. ^ Vander Jagt DL (1989). "15. The glyoxalase system". In Dolphin D, Poulson R, Avramovic O (eds.). Glutathione: Chemical, Biochemical and Medical Aspects. Part A. Coenzymes and cofactors. Wiley. pp. 597–641. ISBN 9780471097846. OCLC 18222786.
  2. ^ a b Farrera, Dominique; Galligan, James (September 2022). "The Human Glyoxalase Gene Family in Health and Disease". Chemical Research in Toxicology. 35 (10): 1766–1776. doi:10.1021/acs.chemrestox.2c00182. PMC 10013676. PMID 36048613.
  3. ^ a b Dixon DP, Cummins L, Cole DJ, Edwards R (June 1998). "Glutathione-mediated detoxification systems in plants". Current Opinion in Plant Biology. 1 (3): 258–66. doi:10.1016/S1369-5266(98)80114-3. PMID 10066594.
  4. ^ Inoue Y, Kimura A (1995). "Methylglyoxal and regulation of its metabolism in microorganisms". Advances in Microbial Physiology. 37: 177–227. doi:10.1016/S0065-2911(08)60146-0. ISBN 9780120277377. PMID 8540421.
  5. ^ Thornalley PJ (December 2003). "Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation". Biochemical Society Transactions. 31 (Pt 6): 1343–8. doi:10.1042/BST0311343. PMID 14641060.
  6. ^ Creighton DJ, Hamilton DS (March 2001). "Brief history of glyoxalase I and what we have learned about metal ion-dependent, enzyme-catalyzed isomerizations". Archives of Biochemistry and Biophysics. 387 (1): 1–10. doi:10.1006/abbi.2000.2253. PMID 11368170.
  7. ^ Vander Jagt DL (May 1993). "Glyoxalase II: molecular characteristics, kinetics and mechanism". Biochemical Society Transactions. 21 (2): 522–7. doi:10.1042/bst0210522. PMID 8359524.