Glutathione transferase omega 1 catalyzes the reduction of S-(phenacyl)glutathiones to acetophenones

Chem Res Toxicol. 2007 Jan;20(1):149-54. doi: 10.1021/tx600305y.

Abstract

S-(Phenacyl)glutathione reductase (SPG-R) plays a significant role in the biotransformation of reactive alpha-haloketones to nontoxic acetophenones. Comparison of the apparent subunit size, amino acid composition, and catalysis of the reduction of S-(phenacyl)glutathiones indicated that a previously described rat SPG-R (Kitada, M., McLenithan, J. C., and Anders, M. W. (1985) J. Biol. Chem. 260, 11749-11754) is homologous to the omega-class glutathione transferase GSTO1-1. The available data show that the SPG-R reaction is catalyzed by GSTO1-1 and not by other GSTs, including the closely related GSTO2-2 isoenzyme. In the proposed reaction mechanism, the active-site cysteine residue of GSTO1-1 reacts with the S-(phenacyl)glutathione substrate to give an acetophenone and a mixed disulfide with the active-site cysteine; a second thiol substrate (e.g., glutathione or 2-mercaptoethanol) reacts with the active-site disulfide to regenerate the catalytically active enzyme and to form a mixed disulfide. A new spectrophotometric assay was developed that allows the rapid determination of SPG-R activity and specific measurement of GSTO1-1 in the presence of other GSTs. This is the first specific reaction attributed to GSTO1-1, and these results demonstrate the catalytic diversity of GSTO1-1, which, in addition to SPG-R activity, catalyzes the reduction of dehydroascorbate and monomethylarsonate(V) and also possesses thioltransferase and GST activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalysis
  • Chromatography, Liquid
  • Cytosol / enzymology
  • Glutathione / metabolism*
  • Glutathione Transferase / metabolism*
  • Hydrogen-Ion Concentration
  • Ketones / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Rats
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Ketones
  • Glutathione Transferase
  • Glutathione