Yount N Y, McNamara D J, Al-Othman A A, Lei K Y
Department of Nutrition and Food Science and the Nutritional Sciences Program, University of Arizona, Tucson, AZ 85721, USA.
J Nutr Biochem. 1990 Jan;1(1):21-7. doi: 10.1016/0955-2863(90)90094-2.
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.
在大鼠中研究了铜缺乏对肝脏3-羟基-3-甲基戊二酰辅酶A还原酶（调节胆固醇生物合成的关键酶）的影响。雄性断乳大鼠喂食含充足、边缘或缺乏水平铜的半纯化日粮6周。进行了两项独立研究；在第一项研究中，动物在分析前禁食12小时，在第二项研究中，动物自由采食日粮。测定血浆脂质水平、肝脏胆固醇浓度以及3-羟基-3-甲基戊二酰辅酶A还原酶的比活性、总量和活性。与先前的研究结果一致，铜缺乏大鼠的血浆总胆固醇和甘油三酯水平显著升高。铜缺乏导致肝脏总胆固醇水平显著降低。在采食的动物中，铜缺乏时3-羟基-3-甲基戊二酰辅酶A还原酶的总量和活性水平升高两倍，该酶的活性形式约占总活性的30%。铜缺乏禁食大鼠的3-羟基-3-甲基戊二酰辅酶A还原酶活性比禁食充足的动物高两倍；然而，禁食确实导致肝脏还原酶比活性降低10倍。这些数据支持了以下假设：铜缺乏会导致大鼠出现高胆固醇血症状态，这与肝脏胆固醇合成增加有关。
