Mallet B, Romette J, Di Costanzo J D
Nouv Presse Med. 1982 Jan 30;11(4):271-4.
Copper is an essential dietary component, being the coenzyme of many enzymes with oxidase activity, e.g. ceruloplasmin, superoxide dismutase, monoamine oxidase, etc. The metabolism of copper is complex and imperfectly known. Active transport of copper through the intestinal epithelial cells involves metallothionein, a protein rich in sulfhydryl groups which also binds the copper in excess and probably prevents absorption in toxic amounts. In hepatocytes a metallothionein facilitates absorption by a similar mechanism and regulates copper distribution in the liver: incorporation in an apoceruloplasmin, storage and synthesis of copper-dependent enzymes. Metallothioneins and ceruloplasmin are essential to adequate copper homeostasis. Apart from genetic disorders, diseases involving copper usually result from hypercupraemia of varied origin. Wilson's disease and Menkes' disease, although clinically and pathogenetically different, are both marked by low ceruloplasmin and copper serum levels. The excessive liver retention of copper in Wilson's disease might be due to increased avidity of hepatic metallothioneins for copper and decreased biliary excretion through lysosomal dysfunction. Menkes' disease might be due to low avidity of intestinal and hepatic metallothioneins for copper. The basic biochemical defect responsible for these two hereditary conditions has not yet been fully elucidated.
铜是一种必需的膳食成分，是许多具有氧化酶活性的酶的辅酶，如铜蓝蛋白、超氧化物歧化酶、单胺氧化酶等。铜的代谢复杂且尚未完全明确。铜通过肠上皮细胞的主动转运涉及金属硫蛋白，这是一种富含巯基的蛋白质，它也能结合过量的铜，并可能阻止有毒量铜的吸收。在肝细胞中，一种金属硫蛋白通过类似机制促进铜的吸收，并调节肝脏中的铜分布：将铜掺入脱辅基铜蓝蛋白、储存以及合成铜依赖性酶。金属硫蛋白和铜蓝蛋白对于维持适当的铜稳态至关重要。除了遗传性疾病外，涉及铜的疾病通常是由各种原因引起的高铜血症导致的。威尔逊病和门克斯病虽然在临床和发病机制上有所不同，但都表现为铜蓝蛋白和血清铜水平降低。威尔逊病中肝脏铜潴留过多可能是由于肝脏金属硫蛋白对铜的亲和力增加以及通过溶酶体功能障碍导致胆汁排泄减少。门克斯病可能是由于肠道和肝脏金属硫蛋白对铜的亲和力较低。导致这两种遗传性疾病的基本生化缺陷尚未完全阐明。
