Evidence that glutathione S-transferases B1B1 and B2B2 are the products of separate genes and that their expression in human liver is subject to inter-individual variation: Molecular relationships between the B1 and B2 subunits and other Alpha class glutathione S-transferases

J D Hayes, L A Kerr, A D Cronshaw

    Research output: Contribution to journalArticle

    81 Citations (Scopus)

    Abstract

    The Alpha class glutathione S-transferases (GSTs) in human liver are composed of polypeptides of Mr 25,900. These enzymes are dimeric, and two immunochemically distinct subunits, B1 and B2, have been described that combine to form GSTs B1B1, B1B2 and B2B2 [Stockman, Beckett & Hayes (1985) Biochem. J. 227, 457-465]. Gradient affinity elution from GSH-Sepharose has been used to resolve the three Alpha class GSTs, and this method has been applied to demonstrate marked inter-individual differences in the hepatic content of GSTs B1B1, B1B2 and B2B2. The B1 and B2 subunits can be resolved by reverse-phase h.p.l.c., and their elution positions suggest that they are equivalent to the alpha chi and alpha y h.p.l.c. peaks described by Ketterer and his colleagues [Ostlund Farrants, Meyer, Coles, Southan, Aitken, Johnson & Ketterer (1987) Biochem. J. 245, 423-428]. The B1 and B2 subunits have now been cleaved with CNBr and the fragments subjected to automated amino acid sequence analysis. The sequence data show that B1 and B2 subunits do not arise from post-translational modification, as had been previously believed for the hepatic Alpha class GSTs, but are instead the products of separate genes; B1 and B2 subunits were found to contain different amino acid residues at positions 88, 110, 111, 112, 116, 124 and 127. The relationship between the B1 and B2 subunits and the cloned GTH1 and GTH2 cDNA sequences [Rhoads, Zarlengo & Tu (1987) Biochem. Biophys. Res. Commun. 145, 474-481] is discussed.

    Original languageEnglish
    Pages (from-to)437-45
    Number of pages9
    JournalBiochemical Journal
    Volume264
    Issue number2
    DOIs
    Publication statusPublished - 1 Dec 1989

    Keywords

    • Adult
    • Amino Acid Sequence
    • Chromatography, High Pressure Liquid
    • Cloning, Molecular
    • DNA/genetics
    • Gene Expression Regulation, Enzymologic
    • Genes
    • Genetic Variation
    • Glutathione Transferase/genetics
    • Humans
    • Isoenzymes/genetics
    • Liver/enzymology
    • Macromolecular Substances
    • Male
    • Molecular Sequence Data
    • Peptide Fragments/isolation & purification
    • Sequence Homology, Nucleic Acid

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