conspectus of researchon copper metabolism and requirements

More documents

Recommendations

Info

1982 KARL E. MASON year Daniels and Wright (142) reported the first balance study on young children (4-6 years old) indicating an average in take of 1.48 mg/day and a requirement not less than 0.10 mg/kg/day. These esti mates are in remarkably good agreement with those recorded in the later literature (see p. 2032). Thus, the stage was set for an extensive exploration of the metab olism, deficiencies, excesses and require ments of copper in man witnessed during the past half century. An overview of what has transpired dur ing this period should include: 1) a vast number of studies on copper depletion and effects of copper supplementation in laboratory animals; 2) recognition of natu rally occurring deficiency of copper in farm animals, especially cattle and sheep, in geo graphic areas where there exists a defi ciency of copper in the soil and vegeta tion; 3) exhaustive analyses of the copper content of plant and animal tissues, in cluding those of man; 4) recognition of states of copper deficiency in the human infant reared on diets similar to those em ployed in inducing copper deficiency states in experimental animals, combined with states of protein calorie malnutrition, in fection and other metabolic disorders; 5) the effects of parenteral alimentation, especially in infants suffering from devel opmental anomalies of the alimentary tract and post-surgical stresses; 6) recognition of two genetically determined abnormali ties of copper metabolism in man ( Menkes' kinky-hair, or steely-hair, syndrome affect ing primarily young infants and Wilson's disease, affecting the adolescent and adult, together with therapeutic measures for the same; and 7) exhaustive studies of the many copper-containing proteins distrib uted throughout the blood and other tissues, and their role in metabolic processes of man and lower animals. In the present review it is not possible to consider the first three categories of re search mentioned above, other than to make reference to certain observations which have particular relevance to the un derstanding of copper metabolism and re quirements of man. For additional infor mation on the first areas of research men tioned the reader is referred to a rather extensive series of reviews (6, 7, 32, 71, 99, 139, 140, 185, 211, 257, 319, 461, 493, 779, 798). COPPER IN THE HUMAN BODY Many opinions have been expressed con cerning the total copper content of the human body. More than 40 years ago Chou and Adolph (115), in studies based upon analyses of nine organs from two adults at autopsy, in which they found an average of about 116 mg, estimated that the human body contained between 100 and 150 mg of copper. Since then estimates have been reduced. Cartwright and Wintrobe (105) considered 80 mg of copper to be a more reasonable estimate for a 70-kg man. Sass- Kortsak (666), on the basis of data of Tipton and Cook (781), calculated a mean of 75 mg, with a range of 50 to 120 mg. A slightly lower estimate of 70 mg has been given recently by Sumino et al. (762), based upon analyses of 18 different organs and tissues of 30 Japanese subjects, victims of accidental deaths, 28 of whom ranged in age from 20 to more than 60 years. These investigators also estimated that about one-third of body copper was in the liver and brain combined, one-third in the musculature, and the remaining third dis persed in other tissues. The mean content of copper in human liver is about \5% of total body copper (668). It has long been recognized that the liver and brain contain a much higher con centration of copper than other organs and tissues, amounting to about 8 mg in each of these organs ( 105). The liver content is, in large part, related to its function as a storage organ for copper and also as the only site of synthesis and release of ceruloplasmin. Copper is unevenly distributed in the brain. While some investigators re port very little difference in the copper content of grey and white matter of the cerebral cortex (102, 138, 613), others have found a considerably higher content in the grey than in the white matter ( 134, 138, 178, 780, 828). The substantia nigra and locus ceruleus, both components of the grey matter, are exceptionally rich in cop per ( 134, 178). Possible relationships of the pigmented nerve cells of the locus ceruleus to their content of melanin and Downloaded from jn.nutrition.org by guest on February 27, 2013
COPPER METABOLISM AND REQUIREMENTS OF MAN 1983 to tyrosinase have been suggested and ex plored by in vitro studies with no positive results, possibly due to the use of necropsy material rather than fresh tissue (178). Gubler et al. (285) record mean copper values (in terms of /*g/g wet weight) of 6.3, 6.5, 5.7, 4.2, 2.6 and 1.7, repsectively, for whole brain, cerebellum, basal ganglia, cerebral cortex, brain stem and cervical spinal cord. These data are based on five adult males who died following traumatic injuries. Compared to the liver and brain, lesser levels of copper are found in the heart, kidney, pancreas, spleen, lungs, bone and skeletal muscle, diminishing generally in the order mentioned (102, 115, 182, 208, 285, 397, 509, 691, 762, 786). Gubler et al. (285 ) give mean values (/Â¿g/gwet weight ) of 5.3, 3.2, 2.2, 1.0 and 0.9, respectively, for liver, heart, kidney, spleen and skeletal muscle. The total copper content of the whole liver, brain, kidney, heart and spleen, respectively, is estimated to be 8.0, 8.0, 1.2, 0.9 and 0.1 mg (105). In the fetus and infant, the distribution of copper is quite different from that in the adult. During fetal life there is a progres sive increase in percentage of copper and iron in the body, while that of zinc re mains relatively constant (704), such that at birth the liver and spleen contain about 1/2 the copper, l/4th the zinc and l/8th the iron in the whole body (846). Liver of the newborn has an exceptionally high con centration of copper, approximately 6 to 10 times that of adult man (538, 844, 846). After the first few months of life these con centrations decrease rapidly to those of the adult (69, 565, 845). During the transition from infancy to the early years of life, there is a decrease in copper concentration in kidney, heart and spleen and an increase in brain (69, 845), which is relatively low in the newborn (780). On the basis of analyses of major organs of man in different geographic areas Forssen (222) states that the Finns have some what lower copper levels than Americans, and that peoples of Africa and the Near and Far East have levels 1.5 to 2 times those of the Finns. Whether these obser vations may or may not reflect differences in soils, dietary habits or ethnic factors is not clear. They are in accord with earlier observations of Schroeder et al. (691) who found that other races have larger mean amounts of copper in aorta, kidney, liver, lung and spleen than do Americans, Swiss and African Caucasoids, and that Orientals have especially high values. The levels of copper in human hair have been the subject of numerous studies in the hope that such information might pro vide some measure of the copper status of the body, especially states of copper de ficiency. Wide individual variations with respect to age and sex (415), to hair pig mentation (357) and to exogenous con tamination (298) have indicated that cop per levels in hair have little meaningfulness in evaluating the status of copper in man (798). However, a recent report (378) states that determination of copper in hair may be useful in evaluating total liver content of copper. COPPER PROTEINS Many proteins in tissues have the ca pacity to form copper complexes. Some of these do not occur in mammalian species, but appear only in lower animal forms and plants (e.g., hemocyanin, lacease, ascorbic acid oxidase, polyphenol oxidases, turacine). There have come to be recognized a large number of cuproproteins of mam malian species in which copper is part of the molecular structure and in which there is a characteristic ratio between moles of protein and atoms of associated copper. By virtue of these characteristics and the fact that the contained copper does not dissociate during isolation of the protein, these cuproproteins function as enzymes and are often grouped with other metalcontaining enzymes, all of which are re ferred to as "metalloproteins." Those ac cepted in this category include ceruloplasmin, Superoxide dismutase, cytochrome c oxidase, lysyl oxidase, tyrosinase and dopamine ÃŸ-hydroxylase. One other important metalloprotein, metallothionein, lacks enzymic properties but is capable of binding copper as well as certain other heavy metals. Several plasma and connective tis sue oxidases isolated from mammalian organs and tissues are at least copper de pendent (monoamine oxidase, spermine Downloaded from jn.nutrition.org by guest on February 27, 2013
Page 1 and 2: A CONSPECTUS OF RESEARCH ON COPPER
Page 3: INTRODUCTION The discovery of coppe
Page 7 and 8: 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 57 and 58:
COPPER METABOLISM AND REQUIREMENTS
Page 59 and 60:
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?