Effect of excess and deficient copper intake on rat liver microsomal enzyme activity

Abstract

The effect of copper loading and copper deficiency on rat liver microsomal enzyme activity was studied. A significant reduction of liver aniline hydroxylase activity was produced by the administration of 450 ppm copper in the drinking water to rats for 15 and 30 days. Lower levels of copper (50 and 150 ppm) administered to rats for the same time had no significant effect on enzyme activity. Copper loading did not alter the activities of liver glucose 6-phosphatase or benzpyrene hydroxylase. Aniline hydroxylase and hexobarbital oxidase activities were significantly reduced, and hexobarbital sleeping time was prolonged in copper-deficient rats. Liver enzyme activities and hexobarbital sleeping times were restored to control levels by feeding copper- deficient rats a copper-containing diet for 14 days. The addition of divalent copper in vitro to 10,000 g supernatants from liver homogenates from copper-deficient rats did not restore enzyme activity to control levels. Instead, high levels of added copper produced a decreased rate of aniline hydroxylation in vitro. Copper deficiency did not prevent the induction of liver microsomal enzyme activity by phenobarbital. Phenobarbital administration significantly increased microsomal copper in rats receiving a normal copper intake and increased both whole liver and microsomal copper concentration in copper-deficient rats. The normal developmental increase in liver aniline hydroxylase and hexobarbital oxidase activities with age was delayed in the offspring of female rats maintained on a copper-deficient diet.