Yount N Y, Carr T P, McNamara D J, Lei K Y
Department of Nutrition and Food Science, University of Arizona, Tucson 85721.
Biochim Biophys Acta. 1991 Feb 26;1082(1):79-84. doi: 10.1016/0005-2760(91)90302-x.
The effect of copper deficiency on absolute rates of cholesterol synthesis was investigated in the rat. Male weanling rats were fed semi-purified diets containing adequate (7.13 ppm) or deficient (0.621 ppm) levels of copper for 6 weeks. Copper-adequate and -deficient animals (n = 6/group) were injected intraperitoneally with 50 mCi 3H-labelled water and killed 1 h post-injection. Copper-deficient animals had elevated heart weights and reduced body and spleen weights. Plasma cholesterol levels were significantly elevated and hematocrits were reduced. Absolute rates of carcass cholesterol synthesis per organ were 1.9-fold higher in copper-deficient rats (P less than 0.025). Previous studies have indicated that hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (E.C.1.1.1.34) activity is increased by copper deficiency; however, de novo synthesis of cholesterol from 3H-labelled water was not significantly elevated in the liver. The present data indicate that newly synthesized cholesterol exported to the plasma was increased 2.1-fold (P less than 0.01) in copper-deficient rats. Since it has been demonstrated that hepatic export of cholesterol is increased with copper deficiency and that the major tissue for export of newly synthesized cholesterol is the liver, we hypothesize that the origin of radiolabeled cholesterol in the plasma was the liver. These data support the hypothesis that elevated levels of hepatic HMG-CoA reductase seen with copper deficiency are associated with an increased rate of whole body and hepatic cholesterol synthesis.
在大鼠中研究了铜缺乏对胆固醇合成绝对速率的影响。雄性断奶大鼠被喂食含适量（7.13 ppm）或缺乏（0.621 ppm）铜水平的半纯化日粮6周。给铜充足和铜缺乏的动物（每组n = 6）腹腔注射50 mCi 3H标记水，并在注射后1小时处死。铜缺乏的动物心脏重量增加，而体重和脾脏重量减轻。血浆胆固醇水平显著升高，血细胞比容降低。铜缺乏大鼠每个器官的胴体胆固醇合成绝对速率高1.9倍（P < 0.025）。先前的研究表明，铜缺乏会增加肝脏3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶（E.C.1.1.1.34）的活性；然而，肝脏中由3H标记水进行的胆固醇从头合成并未显著升高。目前的数据表明，铜缺乏大鼠中输出到血浆的新合成胆固醇增加了2.1倍（P < 0.01）。由于已经证明铜缺乏时肝脏胆固醇输出增加，且新合成胆固醇输出的主要组织是肝脏，我们推测血浆中放射性标记胆固醇的来源是肝脏。这些数据支持以下假设：铜缺乏时肝脏HMG-CoA还原酶水平升高与全身和肝脏胆固醇合成速率增加有关。
