title: Glutathione transferase omega 1 catalyzes the reduction of S-(phenacyl)glutathiones to acetophenones.
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.
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, ACT, 1601 Australia. Philip.Board@anu.edu.au
authors.forename: Philip G
authors.initials: PG
authors.lastname: Board
authors.forename: M W
authors.initials: MW
authors.lastname: Anders
mesh_terms: D000818:Animals; D002384:Catalysis; D002853:Chromatography, Liquid; D003600:Cytosol / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007659:Ketones / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D007659:Ketones; D005982:Glutathione Transferase; D005978:Glutathione