Metabolism copper

Werner s coordination theory, 1, 6 Whewellite structure, 6, 849 Wickmanite structure, 6, 849 Wilkinson s catalyst, 6, 239 Wilson s disease, 5, 721 copper, 6,648 removal, 6,769 copper complexes, 2,959 copper metabolism, 6,766 radiopharmaceutical agents, 6,968 Wolfram s red salt, 5,427 Wurzite... 

Menkes disease ( kinky or steely hair disease) is a disorder of copper metabolism. It is X-hnked, affects... 

Table 50-6. Major laboratory tests used in the investigation of diseases of copper metabolism ...

Wilson s disease A disorder of copper metabolism characterized by cirrhosis of the liver and neurologic manifestations a potentially fatal genetic disorder that causes the body to retain copper. 

In mammals, as in yeast, several different metallothionein isoforms are known, each with a particular tissue distribution (Vasak and Hasler, 2000). Their synthesis is regulated at the level of transcription not only by copper (as well as the other divalent metal ions cadmium, mercury and zinc) but also by hormones, notably steroid hormones, that affect cellular differentiation. Intracellular copper accumulates in metallothionein in copper overload diseases, such as Wilson s disease, forming two distinct molecular forms one with 12 Cu(I) equivalents bound, in which all 20 thiolate ligands of the protein participate in metal binding the other with eight Cu(I)/ metallothionein a molecules, with between 12-14 cysteines involved in Cu(I) coordination (Pountney et ah, 1994). Although the role of specific metallothionein isoforms in zinc homeostasis and apoptosis is established, its primary function in copper metabolism remains enigmatic (Vasak and Hasler, 2000). 

H. Markowitz, G.E. Cartwright, and M.M. Wintrobe, Copper metabolism. XXVII. Isolation and properties of an erythrocyte cuproprotein (erythrocuprein). J. Biol. Chem. 234, 40-45 (1959). 

Abnormalities in copper metabolism are normally associated with Wilson s disease [28] and Menkes disease [29,30,31], although total copper and hCP concentrations increase significantly in many inflammatory and infectious diseases including hepatitis and tuberculosis, and a number of different kinds of cancer. A direct connection between copper and coronary artery disease has also been proposed [32]. A useful general review of copper and disease has been given by Linder [33]. 

This section demonstrates that (1) free ionic copper (Cu2+) is the most toxic chemical species of copper and that copper bioavailability is modified by many biological and abiotic variables (2) copper metabolism and sensitivity to copper of poikilotherms differs from that of mammals and (3) copper interactions with inorganic and organic chemicals are substantial and must be considered when evaluating copper hazards to natural resources. 

Two inherited human diseases that represent abnormal copper metabolism are Menkes syndrome and Wilson s disease. Menkes syndrome, with symptoms similar to those of copper deficiency, is characterized by a progressive brain disease, abnormally low copper concentrations in liver and other tissues, and diminished ability to transfer copper across the absorptive cells of the intestinal mucosa (USEPA 1980 Aaseth and Norseth 1986). Wilson s disease (hepatolenticular degeneration) is the only significant example of copper toxicity in humans. Wilson s disease is an autosomal recessive disorder that affects normal copper homeostasis and is characterized by excessive... 

Sugawara, N., D. Li, M. Katakura, and C. Sugawara. 1994. Biliary excretion of copper in Fischer rats treated with copper salt and in Long-Evans Cinnamon (LEC) rats with an inherently abnormal copper metabolism. Biol. Trace Elem. Res. 46 125-134. 

Yu, S., R.B. Beems, J.A. Joles, G.A. Kaysen, and A.C. Beynen. 1995. Iron and copper metabolism in analbuminaemic rats fed a high-iron diet. Comp. Biochem. Physiol. 110A 131-138. 

Bridges, C.H. 1990. Influence of variable content of dietary zinc on copper metabolism of weanling foals. Amer. Jour. Veterin. Res. 51 275-280. 

Increased urinary excretion, normal serum Mo levels, no change in copper metabolism (11)... 

Cymbaluk, N.F., H.F. Schryver, H.F. Hintz, D.F. Smith, and J.E. Lowe. 1981. Influence of dietary molybdenum on copper metabolism in ponies. Jour. Nutr. 111 96-106. 

Nederbragt, H. 1980. The influence of molybdenum on the copper metabolism of the rat at different Cu levels of the diet. Brit. Jour. Nutr. 43 329-338. 

Suttle, N.F. 1983a. Effects of molybdenum concentration in fresh herbage, hay and semi-purified diets on the copper metabolism of sheep. Jour. Agric. Sci. (Cambridge) 100 651-656. 

Weber, K.M., R.C. Boston, and D.D. Leaver. 1983. The effect of molybdenum and sulfur on the kinetics of copper metabolism in sheep. Austral. Jour. Agric. Res. 34 295-306. 

In contrast, CopB extrudes excess copper (Figure 7.4). Both CopA and CopB belong to the PI subclass of I1-type ATPases, which includes the proteins involved in the human diseases of copper metabolism, Menkes and Wilson s disease (discussed in Chapter 14). 

Contrary to popular belief, ceruloplasmin5, the principal copper-containing protein in plasma, ceruloplasmin, is not involved in copper transport. This is clearly underlined by the clinical observation that patients with aceruloplasminaemia (i.e. lacking ceruloplasmin in their blood) have perfectly normal copper metabolism and homeostasis. Copper is transported in plasma mostly by serum albumin with smaller amounts bound to low-molecular weight ligands like histidine. Likewise zinc is mostly transported in plasma bound to proteins (albumin and ot2-macroglobulin). 

Creutzfeldt-Jakob and other prion diseases have been associated with disorders of copper metabolism. The first cases of Creuzfeldt-Jakob disease in humans were described by Creuzfeldt and Jakob over 80 years ago. Although scrapie was known as a fatal neurological... 

In many crucial biological processes, such as oxygen transport, electron transport, intermediary metabolism, metals play an important part. Therefore, disorders of metal homeostasis, metal bioavailability or toxicity caused by metal excess, are responsible for a large number of human diseases. We have already mentioned disorders of iron metabolism (see Chapter 7) and of copper metabolism (see Chapter 14). The important role, particularly of redox metals such as copper and iron, and also of zinc, in neurodegenerative diseases, such as Parkinson s disease, Alzheimer s disease, etc. has also been discussed (see Chapter 18). We will not further discuss them here. 

G. E. Cartwright, "Copper Metabolism in Human Subjects," in William... 

D. McElroy and Bentley Glass, eds., Copper Metabolism, Johns Hopkins Press, Baltimore, Md., 1950, pp. 274314. 

An excess of zinc will cause problems in humans. Excessive doses can lead to biochemical control system damage, while doses slightly higher than optimal can cause disorders in iron and copper metabolism, resulting in incurable anemia, decrease in activity of zinc protein enzymes, and pancreas and kidney damage (Boularbah et ah, 1999 Seiler et ah, 1994). Increased levels of zinc have been observed in nuclei of neoplastic cells and in cases of acute dental caries, however its role in these diseases has not been explained. 

Zinc is used for a variety of indications. Zinc acetate (8.102) or, rarely, zinc sulfate (8.103) have been used orally to treat Wilson s disease, a recessively inherited disorder of copper metabolism, characterized by brain and liver dysfunction arising from excessive deposits of copper. Zinc pyrithione (8.104) is used in shampoos to treat seborrhea. Zinc propionate (8.105) and zinc caprylate (8.106) have been used as topical antifungal agents. 

---