title: The effect of copper deficiency on rat hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.
abstract: The effect of copper deficiency on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key enzyme regulating cholesterol biosynthesis, was investigated in the rat. Male weanling rats were fed semipurified diets containing adequate, marginal, or deficient levels of copper for 6 weeks. Two separate studies were conducted; in the first study, animals were fasted 12 hours prior to analysis and in the second study, animals were fed diets ad libitum. Plasma lipid levels, hepatic cholesterol concentrations, and 3-hydroxy-3-methylglutaryl coenzyme A reductase specific activity, total and active, were determined. Consistent with previous findings, plasma total cholesterol and triglyceride levels were significantly elevated in copper-deficient rats. Copper deficiency resulted in a significant decrease in hepatic total cholesterol levels. Total and active levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase in fed animals were elevated twofold with copper deficiency, with the active form of the enzyme constituting approximately 30% of total activity. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in copper-deficient fasted rats was twofold higher than for the fasted adequate animal; however, fasting did result in a 10-fold reduction in hepatic reductase specific activity. These data support the hypothesis that copper deficiency results in a hypercholesterolemic state in the rat associated with increased hepatic cholesterol synthesis.
authors.affiliation: Department of Nutrition and Food Science and the Nutritional Sciences Program, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: N Y
authors.initials: NY
authors.lastname: Yount
authors.forename: D J
authors.initials: DJ
authors.lastname: McNamara
authors.forename: A A
authors.initials: AA
authors.lastname: Al-Othman
authors.forename: K Y
authors.initials: KY
authors.lastname: Lei