Involvement of the cystathionine pathway in the biosynthesis of glutathione by isolated rat hepatocytes |
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Authors: | Patrick W. Beatty Donald J. Reed |
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Affiliation: | Oregon State University, Corvallis, Oregon 97331 USA |
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Abstract: | The ability of l-methionine to support glutathione biosynthesis has been investigated in isolated rat hepatocytes under conditions of normal and depleted glutathione status. The addition of l-[35S]methionine or [l-[35S]homocysteine to incubation media containing hepatocytes results in the incorporation of 35S into intracellular glutathione. Additionally both l-methionine and l-homocysteine are capable of supporting the resynthesis of glutathione in isolated hepatocytes after prior depletion with diethyl maleate. The inclusion in the incubation medium of 1 mm propargylglycine, which is an irreversible inhibitor of the terminal enzyme of the cystathionine pathway, substantially blocks the incorporation of 35S from methionine and l-homocysteine into cellular glutathione. Propargylglycine treatment of hepatocytes in the presence of [35S]methionine is shown to result in the intracellular accumulation of [35S]cystathionine. These results strongly support the conclusion that in rat hepatocytes the cystathionine pathway enables methionine to provide a significant source of l-cysteine for the support of glutathione biosynthesis, under both normal and glutathione-depleted conditions. |
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Keywords: | To whom reprint requests should be sent: Department of Biochemistry and Biophysics Oregon State University Corvallis Oreg. 97331. |
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