Glutathione S-transferases: biomedical applications

G J Beckett, J D Hayes

    Research output: Contribution to journalReview articlepeer-review

    265 Citations (Scopus)

    Abstract

    This chapter focuses on the biomedical applications of ubiquitous and modest size enzymes, glutathione S-transferases (GST), found in bacteria, yeast, nematodes, insects, fish, birds, and mammals. They constitute a complex supergene family that collectively metabolizes chemotherapeutic drugs, carcinogens, environmental pollutants, and a broad spectrum of other harmful foreign compounds (xenobiotics). The fact that GST is present at high levels in the liver ensures that their concentration in plasma provides an exceptionally sensitive index of hepatocellular damage. Whereas the function of GST is considered primarily to be one of detoxifying foreign compounds, these enzymes possess activities other than catalyzing the formation of glutathione–xenobiotic conjugates. For example, GST exhibit peroxidase activity toward organic hydroperoxides and serve to combat oxidative stress. The conjugation between reduced glutathione (GSH) and xenobiotics represents the few subsequent steps that lead to the formation of mercapturic acids: the removal of the γ-glutamyl moiety from the glutathione conjugate by γ-glutamyltransferase, the enzymatic removal of glycine from the cysteinyl glycine conjugate, and the N-acetylation of the cysteine conjugate by an acetyl-CoA-linked acetylase. The final N-acetylcysteine thioethers, or mercapturic acids, produced by the enzymes that catalyze this pathway are water soluble and are readily excreted from the body.

    Original languageEnglish
    Pages (from-to)281-380
    Number of pages100
    JournalAdvances in Clinical Chemistry
    Volume30
    DOIs
    Publication statusPublished - 1993

    Keywords

    • Animals
    • Glutathione Transferase/analysis
    • Humans
    • Hyperthyroidism/enzymology
    • Isoenzymes/analysis
    • Kidney/enzymology
    • Liver Diseases/enzymology
    • Neoplasms/enzymology

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