Copper metabolism and the liver.

SITTING as it does astride the portal circulation, the liver is intimately connected with regulating the plasma concentrations of many, if not all, substances absorbed from the gut. Copper is no exception to this rule for although it is, physiologically speaking, a trace metal in man it is an ubiquitous element in nature and is found in many articles of diet and in significant amounts in drinking water since the introduction of copper pipes into household plumbing (surely a word whose etymology has now left it in an untenable position). The normal diet contains 2 to 4 mg. of copper per day and a number of foods are particularly rich in this element, such as shell fish with their copper-containing respiratory pigment, nuts, chocolate, mushrooms, liver and many cereals particularly if these are grown on copper-rich soils. Either by accident or, more probably, by design copper is poorly absorbed from the gut and about 70% of an orally administered dose is recoverable in the faeces (Van Ravestyn, I944). Little copper is excreted in the urine, probably less than 50 ,g. daily by normal adults, and the main route of excretion is via the bile and possibly the gut wall (Adelstein and Valee, I96I). The copper ion is much too reactive to exist free in the body and, for that matter, too powerful an enzyme poison to be allowed to come in contact with the intracellular enzymes (Rees, 1962). Once in contact with protein copper rapidly becomes bound to-SH,-COOH or-NH2 radicles in decreasing order of affinity. Apart from these non-specific copper-protein bindings there are a number of true copper-proteins in the body with a constant copper-protein ratio and, in a number of cases, a known enzyme action, examples being cytochrome C oxidase, tyrosinase and uricase. There are other well documented copper-proteins whose enzyme action or specific function, though such probably exists, is at present unknown, for instance cerebrocuprein, liver-copper-protein erythrocuprein and caeruloplasmin, the blue copper-Although copper, with its integral role in the formation of a number of metallo-proteins, is an essential element in man, there are no well recorded examples of a dietary deficiency of the element such as occur in animals leading to anaemia, demyelinating diseases, myocardial fibrosis, loss of fertility and achromotrichia, the particular manifestion varying with the species (Adelstein and Valee, 1961). The normal body content of the metal is around Ioo mg. (Adelstein and Valee, 1961), the …