Characterization of a class alpha glutathione-S-transferase with glutathione peroxidase activity in human liver microsomes

Arch Biochem Biophys. 2004 Apr 1;424(1):72-80. doi: 10.1016/


A 25.5kDa class alpha glutathione S-transferase (GST) designated as microsomal Ya-GST or M-GSTA has been purified to electrophoretic homogeneity from human liver microsomes. Limited proteolysis, gel filtration chromatography followed by EDTA, and alkaline Na(2)CO(3) treatments of microsomes indicate that the M-GSTA is intrinsic to the microsomes. Western immunoblot analysis revealed that human liver M-GSTA and the previously reported 17-kDa microsomal GST (FEBS Lett. 315 (1993) 77) did not have immunological cross reactivity. The enzyme showed conjugation activity towards substrates like 1-chloro-2,4-nitrobenzene (CDNB) and 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, and 4-hydroxy-2-nonenal (4-HNE), a genotoxic alpha,beta-unsaturated aldehyde product of lipid peroxidation. In addition, the M-GSTA exhibited significant glutathione peroxidase activity towards physiologically relevant fatty acid hydroperoxides as well as phosphatidylcholine hydroperoxide, but not with H(2)O(2). C-terminal amino acid sequence analysis revealed a high homology with the human liver cytosolic GST-A1 and A3 isozymes. Western immunoblot analyses of the microsomes prepared from human hepatoblastoma (HepG2) showed that the expression of this M-GSTA was induced upon treatment with such prooxidants as H(2)O(2), suggesting that it may play an important role in the protection of cellular membranes from peroxidative damage.

MeSH terms

  • Aldehydes / metabolism
  • Amino Acid Sequence
  • Animals
  • Benzene Derivatives / metabolism
  • Cell Line, Tumor
  • Dinitrochlorobenzene / metabolism
  • Dogs
  • Free Radicals / metabolism
  • Gene Expression / drug effects
  • Glutathione Peroxidase / metabolism*
  • Glutathione Transferase / classification
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism*
  • Humans
  • Hydrogen Peroxide / metabolism
  • Isoenzymes / classification
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Lactate Dehydrogenases / metabolism
  • Lipid Peroxides / chemistry
  • Lipid Peroxides / metabolism
  • Microsomes, Liver / enzymology*
  • Oxidants / chemistry
  • Oxidants / pharmacology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sheep
  • Substrate Specificity
  • U937 Cells


  • Aldehydes
  • Benzene Derivatives
  • Dinitrochlorobenzene
  • Free Radicals
  • Isoenzymes
  • Lipid Peroxides
  • Oxidants
  • Recombinant Proteins
  • Hydrogen Peroxide
  • Lactate Dehydrogenases
  • Glutathione Peroxidase
  • Glutathione Transferase
  • 4-hydroxy-2-nonenal
  • cumene hydroperoxide