Abstract
Abstract
Copper deficiency in rats increases hepatic glutathione concentration. The present study was undertaken to determine the biochemical and molecular basis for the glutathione elevation. Weanling Sprague-Dawley rats were fed a purified diet deficient in copper (0.4 μg/g diet) or one containing adequate copper (5.7 μg/g diet) for 4 weeks. Hepatic glutathione concentration, the activity of the rate-limiting enzyme in glutathione biosynthesis, γ-glutamylcysteine synthetase (γ-GCS), and the relative amount of mRNA for the enzyme were determined. Hepatic glutathione concentration in copper-deficient rats was significantly elevated (6.6 vs 5.6 μmol/g). The activity of hepatic γ-GCS was 1.6 times higher in the copper-deficient than in the copper-adequate rats (58.0 vs 35.9 nmol NADH/min · mg protein). The steady-state amount of mRNA for γ-GCS was increased 5-fold in the copper-deficient rat liver. The findings demonstrate that the elevated hepatic glutathione concentration in copper-deficient rats results from upregulation of γ-GCS activity. This study provides further understanding of changes in hepatic glutathione metabolism induced by copper deficiency.
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