Keen C L, Cohen N L, Hurley L S, Lönnerdal B
Biochem Biophys Res Commun. 1984 Feb 14;118(3):697-703. doi: 10.1016/0006-291x(84)91450-5.
The teratogenicity of copper deficiency is well known, but underlying mechanisms have not been delineated. One method of studying the biochemical lesions of copper deficiency is the use of chelating drugs with different chemical characteristics. The teratogenicity of a copper deficient diet and of diets containing either D-penicillamine or triethylenetetramine is quite different, although all three diets result in decreased fetal liver copper levels. Feeding D-penicillamine can result in decreased fetal liver zinc, while feeding triethylenetetramine can result in increased fetal liver zinc. The effect of these three diets on fetal liver copper and zinc molecular localization was determined. Gel filtration showed that fetal liver copper and zinc in controls was localized in 3 fractions with MWs of greater than 50,000 (H), 30,000 (I) and 8-10,000 (L). Independent of dietary treatment, as liver copper diminished, copper was missing first from the L peak, then the I peak and with severe deficiency, from the H peak. Drug induced increases and decreases in fetal liver zinc were reflected in the L peak. These data suggest that the absolute levels of copper in the liver of the term fetus determines the distribution of the element among its binding ligands.
铜缺乏的致畸性是众所周知的，但潜在机制尚未明确。研究铜缺乏生化损伤的一种方法是使用具有不同化学特性的螯合药物。尽管三种饮食都会导致胎儿肝脏铜水平降低，但缺铜饮食以及含有D-青霉胺或三亚乙基四胺的饮食的致畸性却大不相同。喂食D-青霉胺会导致胎儿肝脏锌含量降低，而喂食三亚乙基四胺会导致胎儿肝脏锌含量增加。确定了这三种饮食对胎儿肝脏铜和锌分子定位的影响。凝胶过滤显示，对照组胎儿肝脏中的铜和锌定位于分子量大于50,000（H）、30,000（I）和8 - 10,000（L）的三个组分中。与饮食处理无关，随着肝脏铜含量减少，铜首先从L峰消失，然后是I峰，严重缺乏时从H峰消失。药物诱导的胎儿肝脏锌含量的增加和减少反映在L峰中。这些数据表明，足月胎儿肝脏中铜的绝对水平决定了该元素在其结合配体之间的分布。
