ABSTRACT
Copper is a heavy metal that is an essential cofactor for several important enzymes in humans. Known as cuproenzymes, these enzymes include cytochrome C oxidase (electron transport chain), dopamine b-hydroxylase (catecholamine synthesis), superoxide mutase (detoxification of free radicals), and lysyl oxidase (formation of collagen). The main source of copper is copper-containing foods, high quality sources being shellfish, nuts, chocolate, mushrooms, and liver. In the intestines, copper is transported into enterocytes and then transferred to the portal circulation by one of two mechanisms. Copper may bind to metallothioneins, proteins that bind metals, and then be transported to the liver. Alternatively, copper can be actively transported across the basolateral membrane of the enterocytes where it then binds to albumin and other proteins in blood. It is then transported to the liver through the portal circulation. Menkes disease is an X-linked disorder due to mutations in the gene ATP7A that encodes the ATPase-dependent copper transporter on the basolateral membrane of the enterocytes. In this disorder, there is a buildup of copper in enterocytes, leading to a secondary systemic copper deficiency. Without adequate copper, cuproenzyme function is impaired and the symptoms of Menkes disease develop.
