conspectus of researchon copper metabolism and requirements

More documents

Recommendations

Info

1986 KARL E. MASON min also has the capacity to oxidize natu rally occurring substances such as sero tonin, melatonin, epinephrine and norepinephrine, and may possibly play an important role in the control of blood and tissue levels of biogenic amines (585). There are also suggestions that abnormali ties in copper metabolism may be involved in Parkinson's disease (34). For further details concerning the multifunctional na ture of ceruloplasmin, its biological func tions and catalytic activity the reader is referred to the recent reviews of Frieden and Hsieh (230) and of Sass-Kortsak and Beam (668). Ceruloplasmin is not the only compound with ferroxidase-like activity in human plasma. In 1969, Lee et al. (444) reported the presence of citrate, differing from ceruloplasmin in that it is not inhibited by azide and yet has the same capacity to accelerate oxidation of ferrous ion to ferric ion and, possibly, to accelerate the rate of reaction of ferric ion with transferrin. Ad ditional mechanisms, perhaps not involving copper directly, have been implicated in iron translocation (56a). A deterrent to recognition of a role of ceruloplasmin in hematopoietic functions of man has been the finding that many subjects suffering from Wilson's disease may have no demon strable plasma ceruloplasmin and yet show no evidence of iron-deficiency anemia. This anomaly seems now to have a reason able explanation with the isolation of an other cuproprotein from human serum by Topham and Frieden (788) which nor mally accounts for about 1% of the total ferroxidase activity. It has a molecular weight of about 800,000 daltpns and con tains approximately 0.8% copper. Its desig nation as ferroxidase II seems quite appro priate. It is a lipoprotein with a cholesterol and phosphatidylcholine content of ap proximately 207o- It differs from cerulo plasmin also in its yellow color and its lack of p-phenylenediamine oxidase activity, and may be responsible for the mainte nance of near-normal iron metabolism, despite low-levels or absence of plasma ceruloplasmin, in Wilson's disease. Whether citrate plays a comparable role is still a question. Furthermore, most of the new postulations with respect to the roles of the ferroxidases and citrate are based upon in vitro studies on human blood and observa tions on experimental animals. Their appli cability to man seems reasonable but re mains to be established. Other intriguing aspects of ceruloplas min are: 1) its increased plasma levels in response to estrogenic hormones, as in users of oral contraceptives and pregnant women; 2) its very low levels in plasma of the fetus and newborn; 3) its rapid synthesis by the newborn infant through utilization of a special neonatal hepatomitochondrocuprein not found at any other stage of life; 4) its stabilization at adult plasma levels at or about puberty; 5) its low serum levels in the genetically deter mined Wilson's and Menkes' diseases; and 6) suggestions that copper is incor porated into cytochrome c oxidase only if it is presented to the cell as ceruloplasmin (3, 65). These topics will be considered later. Superoxide dismutase Almost 40 years ago, Mann and Keilin (486) isolated two blue copper proteins from bovine erythrocytes and liver which they designated hemocuprein and hepatocuprein, respectively. Both proteins had molecular weights of about 35,000 daltons and contained 0.34% copper. Similar pro teins were later isolated from human eryth rocytes (erythrocuprein) by Markowitz et al. (490), from human brain (cerebrocuprein) by Porter and Ainsworth (612) and from adult human liver (hepatocuprein) by Porter et al. (616). Subsequently, Carneo and Deutsch (95) clearly demonstrated that these copper proteins were identical and proposed the term cytocuprein to encompass them. They later considered the term inappropriate, since the protein also contained 2-g atoms of zinc per mole (96). On the basis that these cuproproteins catalyze the dismutation of superoxide-free radical ions, and thus have true enzymatic function, the designation "superoxide dismutase" was proposed by McCord and Fridovich (500, 501), and is now in common usage. The primary function of superoxide dismutase appears to be that of scavenging the inter mediates of oxygen reduction in aerobic Downloaded from jn.nutrition.org by guest on February 27, 2013
COPPER METABOLISM AND REQUIREMENTS OF MAN 1987 organisms, namely Superoxide aniÃ³nradical (500). Superoxide dismutase catalyzes the conversion of the Superoxide radical to hydrogen peroxide plus oxygen and the hydrogen peroxide is removed by catalyses and peroxidases. Thus, Superoxide dismu tase helps protect the cell from the damag ing effects of oxygen toxicity. Cytochrome c oxidase Although cytochrome c oxidase has been recognized as a copper and heme contain ing protein for almost 40 years, the state and function of its copper component have been very difficult to clarify. The history of these explorations, up to 1966, has been well reviewed by Beinert (43) and Wharton and Gibson (837). It has not yet been possible to clearly establish its molecular weight, or whether it contains one or two copper ions and one or two heme groups. This enzyme is found in all aerobic cells and is mainly responsible for the introduc tion of oxygen into the oxidative machinery that produces energy for biochemical syn thesis and for physical activity. As the terminal enzyme in the electron transport chain, it catalyzes the oxidation of reduced cytochrome c by molecular oxygen and, in the process, oxygen is reduced to water. It represents an enzyme vital to essentially all forms of life, by virtue of serving as the terminal enzyme in the oxidative phosphorylation process of living cells. A significant decrease in cytochrome c oxidase activity is considered a major cause of neural and cardiac abnormalities ob served in the offspring of different animal species fed diets deficient in copper. Neural lesions varying from defective myelination to necrosis occur in lambs and goats (361, 798), in the guinea pig (201, 202) and in the rat (92, 401 ). Myocardial abnormalities ranging from focal failure of tissue respi ration to myocardial hypertrophy and acute cardiac failure occur in cattle (798), swine (707) and rats (3, 92, 241, 316). Lysyl oxidase This copper-containing enzyme, lysyl oxidase, is one of the amine oxidases (308 ) but is given separate consideration here because of its well established status and special importance. It has now been par tially purified from several sources (308, 601, 648a, 650, 716). Its major function appears to be to catalyze the oxidative deamination of e-amino groups of peptidyl lysine or hydroxylysine to form Â«-aminoadipic-S-semialdehyde derivatives as a first step in the cross-linking of immature elastin and collagen into stabile fibrils. In collagen, the cross-links are derived from either ly sine or hydroxylysine. In elastin, however, hydroxylysine and hydroxylysine-derived cross-links are not present. The story of lysyl oxidase goes back to early studies of experimental copper-defi ciency in the chick (331, 571, 734) and pigs (93, 94, 129, 707) in which dissecting aneurisms and sometimes rupture of the aorta and large vessels were noted. These vascular defects were ascribed to abnor malities of the elastic component of the vascular wall and to low tissue levels of copper. These observations coincided in time with the demonstration by Partridge et al. (594) that the vital crosslinking groups in elastin, which they named "desmosine" and "isodesmosine," were formed from lysine. Other studies on copper-defi cient chicks (117) gave evidence of a role of copper in crosslinking of collagen. It is now clear that the basis for these observa tions was the role of copper as a cofactor for lysyl oxidase (648a). Further, a foundation was laid for the development of current concepts related to the role of copper with respect to bio chemical and structural abnormalities seen in collagen and elastin in experimental ani mals, livestock (798) and non-domestic animals (219). Furthermore, one can ob serve an example of application of knowl edge gained from experimentally induced deficiency in the chick and lower animals to a better understanding of human dis orders, since many of the manifestations of Menkes' kinky-hair syndrome (513), a congenital state of copper-deficiency in young children, are also characterized by vascular and skeletal defects. For further details, the reader is referred to several recent reviews (93, 130, 568-570, 648a, 650) and top. 2009. Tyrosinase ( phenoloxidase ) This cuproprotein enzyme contains about Q.2c/f copper, or 1 atom per molecule (68), Downloaded from jn.nutrition.org by guest on February 27, 2013
Page 1 and 2: A CONSPECTUS OF RESEARCH ON COPPER
Page 3 and 4: INTRODUCTION The discovery of coppe
Page 5 and 6: COPPER METABOLISM AND REQUIREMENTS
Page 7: COPPER METABOLISM AND REQUIREMENTS
Page 53 and 54: s &5Â°.S0 0lÃ¬Â»"oPH o^â€
Page 55 and 56: Ã®1co 1stW Â»aÂ«a3 COPPER MET
Page 59 and 60:
COPPER METABOLISM AND REQUIREMENTS
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
show all

conspectus of researchon copper metabolism and requirements

Create successful ePaper yourself

Delete template?

Save as template?