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

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    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

    Fingerprint

    Glutathione Transferase
    Liver
    Genes
    Gene Expression
    Protein Sequence Analysis
    Post Translational Protein Processing
    Individuality
    Sepharose
    Amino Acids
    Complementary DNA
    Peptides
    Enzymes
    glutathione S-transferase alpha

    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

    Cite this

    @article{802f032030eb456aac3b5c3982b3f7fc,
    title = "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",
    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.",
    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",
    author = "Hayes, {J D} and Kerr, {L A} and Cronshaw, {A D}",
    year = "1989",
    month = "12",
    day = "1",
    doi = "10.1042/bj2640437",
    language = "English",
    volume = "264",
    pages = "437--45",
    journal = "Biochemical Journal",
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    }

    TY - JOUR

    T1 - 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

    T2 - Molecular relationships between the B1 and B2 subunits and other Alpha class glutathione S-transferases

    AU - Hayes, J D

    AU - Kerr, L A

    AU - Cronshaw, A D

    PY - 1989/12/1

    Y1 - 1989/12/1

    N2 - 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.

    AB - 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.

    KW - Adult

    KW - Amino Acid Sequence

    KW - Chromatography, High Pressure Liquid

    KW - Cloning, Molecular

    KW - DNA/genetics

    KW - Gene Expression Regulation, Enzymologic

    KW - Genes

    KW - Genetic Variation

    KW - Glutathione Transferase/genetics

    KW - Humans

    KW - Isoenzymes/genetics

    KW - Liver/enzymology

    KW - Macromolecular Substances

    KW - Male

    KW - Molecular Sequence Data

    KW - Peptide Fragments/isolation & purification

    KW - Sequence Homology, Nucleic Acid

    U2 - 10.1042/bj2640437

    DO - 10.1042/bj2640437

    M3 - Article

    C2 - 2604726

    VL - 264

    SP - 437

    EP - 445

    JO - Biochemical Journal

    JF - Biochemical Journal

    SN - 0264-6021

    IS - 2

    ER -