Chemical Basis of the Action of Glyoxalase I, an Anticancer Target Enzyme

Kenneth T. Douglas, Seiji Shinkai

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

Although glyoxalase I was discovered in 1913 the physiological role of this ubiquitous enzyme is still far from clear. It catalyzes the reaction of α‐ketoaldehydes and glutathione to produce S‐D‐lactoylglutathione, from which D‐lactate and glutathione are produced by glyoxalase II. Argument raged for many decades about the nature of the natural substrate. Was it methylglyoxal? Was methylglyoxal ever formed metabolically or was it purely artifactual? Some of these questions have been resolved in that a number of metabolic processes which produce α‐ketoaldehydes have now been recognized. Equally unsuccessful have been attempts to ascribe a physiological role to glyoxalase. This is clearly an important question since glyoxalase I occurs in cells at all levels of evolution. Time and time again glyoxalase I has been claimed to be linked to cancer, and a number of research groups worldwide are using it as a model for designing potential anticancer drugs. In this review article the mechanism of action of the enzyme is discussed, knowledge of which enables stronger inhibitors to be synthesized. Until roughly ten years ago when powerful NMR techniques were used to study it for the first time, it was assumed that the key step in the mechanism was a hydride ion transfer. Today, the mechanism is envisaged as a proton transfer.

Original languageEnglish
Pages (from-to)31-44
Number of pages14
JournalAngewandte Chemie International Edition in English
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 1 1985

Fingerprint

Lactoylglutathione Lyase
Pyruvaldehyde
Enzymes
hydroxyacylglutathione hydrolase
Proton transfer
Glutathione
Hydrides
Nuclear magnetic resonance
Ions
Substrates
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Cite this

Chemical Basis of the Action of Glyoxalase I, an Anticancer Target Enzyme. / Douglas, Kenneth T.; Shinkai, Seiji.

In: Angewandte Chemie International Edition in English, Vol. 24, No. 1, 01.01.1985, p. 31-44.

Research output: Contribution to journalReview article

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