conspectus of researchon copper metabolism and requirements

More documents

Recommendations

Info

1996 KARL E. MASON enterohepatic circulation of copper, con sidered unlikely on the basis of the macromolecular complexes of copper predomi nating in the gall bladder bile (266), now justifies more critical study. More recently evidence has been found that the mechanism of copper excretion may involve its complexing with taurochenodeoxycholate in the liver, thereby preventing its reabsorption from the upper intestine, with subsequent splitting of the complex in the lower intestine where reabsorption of the bile acid but not of cop per may take place (454). Other evidence, also based upon bile from T-tubes, sug gests that orally administered 04Cu be comes combined with conjugated bilirubins (503 ). It is obvious that there is still much more to be learned about the binding of copper in bile and its possible reabsorbability. Salivary excretion Little or no attention had been given to the presence of copper in saliva until 1952 when Dreizen et al. ( 170) reported finding in the whole saliva of 14 normal humans (48 samples) a mean copper concentration of 25.6 /Ag/100 ml. In general agreement with these findings are those of De Jorge et al. (157) based on 40 normal, fasting subjects, giving a mean value of 31.7 /Â¿g/ 100 ml, and of Gollan et al. (264) based on 18 normal subjects and providing a mean value of 29 /Â¿g/100ml. The ' copper of saliva is in the labile form, since reactions for ceruloplasmin are negative (157). If one considers the daily output of saliva to be 1.5 liters (range 1-2 liters), the total daily excretion of copper would amount to from 0.38 to 0.47 mg, on the basis of the data recorded above. There is also evi dence that the copper-binding substances in saliva retain their activity after transit through the stomach to the site of absorp tion in the small intestine. De Jorge et al. (157) also report mean copper values of submaxillary, parotid and pancreas re moved from 10 postmortem cases as 1.43, 0.55 and 0.85 mg/100 g dry weight of tis sue, respectively. Gastrointestinal excretion In his pioneer studies on the metabolism of copper in man, Van Ravensteyn (805) found an average copper concentration of 0.023 mg/100 ml (range 0.01-0.04 mg/100 ml) in gastric juice of eight normal sub jects. Some 27 years later, other data were provided by Gollan et al. (265) who, in four normal subjects, found a mean con centration of 0.034 mg/100 ml (range 0.02- 0.96 mg/100 ml). In the latter studies gastric juice free of swallowed saliva and nasopharyngeal secretions was aspirated from fasting subjects, and particulate mat ter was removed by centrifugation at 2,000 X g for 20 minutes. Accepting the values reported by Gollan et al. (265), employing exacting collecting and analytical pro cedures, and considering current estimates that the daily volume of gastric secretions approximates 3 liters (range 2-4 liters), it can be calculated that the gastric mucosa secretes approximately 1.0 mg/day. The only recorded study of duodenal secretion of copper is that of Gollan (263 ). Normal and secretin-stimulated aspirates of the duodenum, obtained from fasting normal subjects through a tube positioned such as to exclude gastric contents (and presumably to also exclude bile and pan creatic secretions) indicates the presence of copper-binding substances of low molec ular weight such as also found in saliva and gastric juice. Gollan presents evidence that the latter binding substances retain their activity after transit through the stomach to the site of absorption in the small intestine. He also postulates that these secretions, through their capacity to solubilize the metal at an alkaline pH, may enhance the availability of copper for ab sorption. Relatively little attention has been given to, or estimates made of, the amount of copper released into the feces via the ex tensive dehiscence of epithelial cells of the intestinal mucosa. In these cells there is a considerable amount of copper bound to metallothionein or metallothionein-like pro teins, functioning in copper storage and in protection against excess copper intake. Considering that the absorptive cells lining intestinal villi are replaced every 5 to 6 days in man (475), this contribution of copper to the intestinal contents and to the fecal output may be quite significant, since it is thought to be nonabsorbable Downloaded from jn.nutrition.org by guest on February 27, 2013
COPPER METABOLISM AND REQUIREMENTS OF MAN 1997 (192). It may represent 17% of the daily fecal excretion (301). It certainly justifies more consideration as a factor in evaluat ing copper excretion and maintenance of copper balance in the human organism. Questions arise concerning the fate of the large amount of copper bound to sub stances of low molecular weight (amino acids and peptides) which is excreted via the saliva, gastric juice and duodenal se cretions. Unfortunately, studies presented record many data but make few predic tions as to what the findings may mean with regard to copper absorption or metab olism. Some of this copper may be reabsorbed and some may be added to the fÃ¨ces, but the relative amounts are un known. And, in addition, the physiological catabolism of ceruloplasmin may add about 0.1 mg to fecal excretion of copper per day (814). Urinary excretion Estimates of copper lost in the urine are somewhat variable, apparently due to dif ferences in sensitivity and accuracy of methods used, and possible contamination from extraneous sources. Early reports are summarized by Butler and Newman (83) who, in a study of 12 healthy adults, re ported mean excretion values of 18.0 jug/ day, (range 3.9-29.6 fig/day). Values re ported since that time are in reasonable accord with these results. If one selects from the literature those reports based upon 10 or more adult subjects, chrono logically recording results in terms of /Â«.g/dayexcreted in the urine, the values are: 18 (113); 18 (765); 20 (253); 37 (398) and 52 (153). These values are all within the range of 10 to 60 /Â¿g/daypro posed by Cartwright and Wintrobe ( 106). Thus, urinary excretion of copper, amount ing to approximately 0.5 to 3.0$ of the daily intake, places the main excretory re sponsibility on fecal excretion. There still remains the possibility that the human kidney possesses the capacity for tubular reabsorption of copper. Sweat loss The loss of copper through sweat has received limited consideration. The pioneer studies of Consolazio et al. ( 122) record that on a constant dietary intake of copper (3.5 mg) and in an environment of 37.8Â° and humidity of 50$;, three normal sub jects showed a significant negative copper balance. During 10 days of observation the sweat loss from the men averaged 1.6 mg/ day, or about 45% of their total dietary in take. Consequently, the negative balance averaged 1.1 mg/day. Mitchell and Hamil ton (528) found an average of 58 /Â¿g/li ter in the sweat of four adult males under hot, humid conditions. Another report (343) records for 33 males after sauna bathing an average excretion of 550 Â±350 /^g/liter in the sweat. In view of these data it ap pears that the loss of copper through sweat is much greater than heretofore recog nized. In fact, Hohnadel et al. (343) and Sunderman et al. (764) extol the possible virtues of the sauna bath as a therapeutic method for increasing the excretion of toxic metals, such as copper in Wilson's disease. Technical methods defy measurements of copper loss through insensible perspiration. Menstrual loss Data on the loss of copper via menstrual flow is likewise meager. For four menstrual periods in three subjects values of 0.19, 0.24, 0.39 and 0.61 mg per period (aver. 0.47 mg) are given by Ohlson and Daum (572). Comparable average values of 0.32, 0.48, 0.65 and 0.74 mg copper for four consecutive periods in four different sub jects are recorded by Leverton and Binkley (452), and a mean of 0.11 Â±0.07 mg per period for 12 adolescent girls is re ported by Greger and Buckley (278 ). COPPER IN THE DIET Copper in foods Copper is ubiquitous in plants and ani mals. Its widespread occurrence in food was demonstrated in the early reports of Lindow et al. (462) and of Hodges and Peterson (341) on the copper-content of samples of commonly used food in the USA, and that of Adolph and Chou (8) on Chinese foods. It is well recognized that the copper in foods varies greatly, depend ing upon the soils from which they have been obtained, and on contamination be fore and after reaching the market place. 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 17: 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 69 and 70:
COPPER METABOLISM AND REQUIREMENTS
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?