EXPRESSION OF GAMMA-GLUTAMYLCYSTEINE SYNTHETASE IN THE LIVER OF COPPER-DEFICIENT RATS

Copper deficiency in rats increases hepatic glutathione concentration. The present study was undertaken to determine the biochemical and mol ecular basis for the glutathione elevation. Weanling Sprague-Dawley ra ts were fed a purified diet deficient in copper (0.4 mu g/g diet) or o ne containing adequate copper (5.7 mu g/g diet) for 4 weeks. Hepatic g lutathione concentration, the activity of the rate-limiting enzyme in glutathione biosynthesis, gamma-glutamylcysteine synthetase (gamma-GCS ), and the relative amount of mRNA for the enzyme were determined. Hep atic glutathione concentration in copper deficient rats was significan tly elevated (6.6 vs 5.6 mu mol/g). The activity of hepatic gamma-GCS was 1.6 times higher in the copper deficient than in the copper-adequa te rats (58.0 vs 35.9 nmol NADH/min . mg protein). The steady-state am ount of mRNA for gamma-GCS was increased B-fold in the copper-deficien t rat liver. The findings demonstrate that the elevated hepatic glutat hione concentration in copper-deficient rats results from upregulation of gamma-GCS activity. This study provides further understanding of c hanges in hepatic glutathione metabolism induced by copper deficiency.