Role of hepatic γ-glutamyltransferase in the degradation of circulating glutathione: Studies in the intact guinea pig perfused liver

Authors

  • Hernan Speisky,

    1. Departments of Pharmacology and Medicine, University of Toronto and Addiction Research Foundation, Toronto, Ontario, M5S 2S1, Canada
    2. Department of Pharmacology, Faculty of Chemistry, Catholic University of Chile, Santiago, Chile
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  • Nick Shackel,

    1. School of Physiology and Pharmacology, University of New South Wales and Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Darlinghurst, 2010, N. S. W., Australia
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  • George Varghese,

    1. Departments of Pharmacology and Medicine, University of Toronto and Addiction Research Foundation, Toronto, Ontario, M5S 2S1, Canada
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  • Denis Wade,

    1. School of Physiology and Pharmacology, University of New South Wales and Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Darlinghurst, 2010, N. S. W., Australia
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  • Dr. Yedy Israel

    Corresponding author
    1. Departments of Pharmacology and Medicine, University of Toronto and Addiction Research Foundation, Toronto, Ontario, M5S 2S1, Canada
    • Department of Pharmacology, Medical Sciences Building, University of Toronto, Ontario, Canada M5S 1A8
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Abstract

The role of hepatic γ-glutamyltransferase in the breakdown of circulating glutathione was studied in the perfused guinea pig liver. Hepatic γ-glutamyltransferase activity in the guinea pig is sevenfold higher than in the rat and is comparable to its activity in man. Guinea pig livers were found to remove, in a single pass, 50% to 90% of glutathione ( 10 to 50 μmol/L) added to the portal perfusate. Removal of portal glutathione was totally dependent on the activity of γ-glutamyltransferase and led to the near quantitative appearance of cysteinyl-glycine and cysteine in the caval perfusate. Glutathione removal by the intact liver followed saturation with a Michaelis constant (Km) of 59 μmol/L for glutathione and a maximum velocity of 235 nmol glutathione/min/gm of liver weight. The capacity of the guinea pig liver to remove circulating glutathione was estimated to be sevenfold to 10-fold higher than its net rate of output of glutathione into the circulation. Inhibition of γ-glutamyltransferase activity in the perfused liver led to threefold to sixfold increases in the hepatic output of glutathione into the circulation, indicating that more than two thirds of glutathione transported extracellularly is broken down. Data obtained demonstrate a major role of hepatic γ-glutamyltransferase, both in the removal of portally carried glutathione and in the degradation of glutathione molecules released by the liver itself into the sinusoids. These findings suggest the existence of an intraorgan transport of glutathione in the liver, whereby periportal cells could provide glutathione precursors to pericentral cells.(HEPATOLOGY 1990; 11:843-849.)

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