Zinc Binding Ligands and Complexes in Zinc Metabolism

  • Bo Lönnerdal
  • Carl L. Keen
  • Lucille S. Hurley
Part of the Advances in Nutritional Research book series (ASIB, volume 110)


The essential role of the trace element zinc in both the prenatal and post-natal periods of mammalian development has been well documented (Underwood, 1977; Hurley, 1980; Prasad, 1976). Zinc is important in many ways: it is required for the activity of numerous enzymes (Parisi and Yallee, 1969), and is important for stability of biological membranes (Chvapil, 1973), for integrity and synthesis of nucleic acids (Dreosti et al., 1972; Dreosti and Hurley, 1975; Eckhert and Hurley, 1977; Eichhorn et al., 1973), and for synthesis of proteins and lipids (Underwood, 1977). Based on the large number of important reactions that involve zinc, it is reasonable to suppose that metabolism of this element is under some regulation. It has been suggested that the primary site of zinc homeostasis is the intestine (Cotzias et al., 1962; Cousins, 1979a, 1979b; Weigand and Kirchgessner, 1976a, 1976b, 1980). Currently, most investigators think that zinc homeostasis in the intestine, occurring through absorption or excretion of the element (or both), is mediated in part by low molecular weight (LMW) ligands. This area of nutrition research has been the subject of considerable recent interest, especially because of reports of dietary zinc deficiency in various age groups of several human populations (Prasad, 1976; Hambidge et al., 1972, 1976; Jameson, 1976, 1981). Zinc deficiency in humans has been correlated with a number of disorders, including congenital malformations and complications of pregnancy, poor growth and development during infancy, childhood, and adolescence, and impaired immunocompetence.


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  1. Aggett, P.J., Fenwick, P.K., and Kirk, H., 1982, A study in vitroof the effect of picolinic acid on metal translocation across model membranes, Proc. Nutr. Soc. 41: 68A.Google Scholar
  2. Andresen, E., Flagstad, T., Basse, A., and Brummerstedt, E., 1970, Evidence of a lethal trait, A46, in Black Pied Danish Cattle of Friesian descent, Nord. Vet. Med. 22: 473.Google Scholar
  3. Andresen, E., Basse, A., Brummerstedt, E., and Flagstad, T., 1974, Lethal trait A46 in cattle. Additional genetic investigations, Nord. Yet. Med 26: 275.Google Scholar
  4. Antonson, D.L., Barak, A.J., and Vanderhoof, J.A., 1979, Determination of the site of zinc absorption in rat small intestine, J. Nutr 109: 142.Google Scholar
  5. Atherton, D.J., Muller, D.P.R., Aggett, P.J., and Harries, J.T., 1979, A defect in zinc uptake by jejunal biopsies in acrodermatitis enteropathica, Clin. Sci 56: 505.Google Scholar
  6. Beach, R.S., Gershwin, M.E., and Hurley, L.S., 1980, T cell function in the lethal milk (lm/lm) mutant mouse, in: Immunology 80: Fourth International Congress of Immunology( M. Fougereau and J. Dausset, eds.), Academic Press, New York.Google Scholar
  7. Berggren, L., and Hansson, O., 1966, Treating acrodermatitis enteropathica, Lancet 1: 52.Google Scholar
  8. Bergsma, D., 1973, in: Birth Defects, Williams and Wilkins, Baltimore.Google Scholar
  9. Bernstein, B., and Leyden, J.J., 1978, Zinc deficiency and acrodermatitis after intravenous hyperalimentation, Arch. Dermatol. 114: 1070.Google Scholar
  10. Birnstiegl, M., Stone, B., and Richards, V., 1956, Excretion of radioactive zinc (Zn65) in bile, pancreatic and duodenal secretions of the dog, Am. J. Physiol 186: 377.Google Scholar
  11. Blakeborough, P., Salter, D.N., and Gurr, W.I., 1981, Zinc binding in human and cow’s milk, in: Nutrition in Health and Disease and International Development: symposia from the 12th International Congress of Nutrition (A.E. Harper and G.K. Davis, eds.), no. 957, Liss, New York.Google Scholar
  12. Bosma, A.A., and Kroneman, J., 1979, Chromosome studies in cattle with hereditary zinc deficiency (lethal trait A46), Vet. Quart 1: 121.Google Scholar
  13. Brandt, T., 1936, Dermatitis in children with disturbances of the general condition and the absorption of food elements, Acta Derm. Venereol. 17: 513.Google Scholar
  14. Brazin, S.A., Johnson, W.T., and Abramson, L.J., 1979, The acrodermatitis enteropathica like syndrome, Arch. Dermatol 115: 597.Google Scholar
  15. Brise, H., and Hallberg, L., 1962, Absorbability of different iron compounds, Acta Med. Scand. 171:Suppl. 376, 23.Google Scholar
  16. Brown, R.G., Hoag, G.N., Smart, M.E., Boechner, G., and Subden, R.E., 1977, Alaskan malamute chondrodysplasia. IV. Concentrations of zinc, copper, and iron in various tissues, Growth 41: 215.Google Scholar
  17. Brown, R.G., Hoag, G.N., Smart, M.E., and Mitchell, L.H., 1978, Alaskan malamute chondrodysplasia. V. Decreased gut zinc absorption, Growth 42: 1.Google Scholar
  18. Brummerstedt, E., Flagstad, T., Basse, A., and Andresen, E., 1971, The effect of zinc on calves with hereditary thymus hypoplasia (lethal trait A46), Acta Path. Microbiol. Scand., section A 79: 686.Google Scholar
  19. Brummerstedt, E., Andresen, E., Basse, A., and Flagstad, T., 1974, Lethal trait A46 in cattle. Immunological investigations, Nord Vet-Med. 26: 279.Google Scholar
  20. Canfield, W., Lykken, G., Milne, D., and Sandstead, H., 1982, Effect of oral picolinic acid on 65Zn retention in normal men, Am. J. Clin. Nutr 35: 843.Google Scholar
  21. Casey, C.E., Hambidge, K.M., Walravens, P.A., Silverman, A., and Neldner, K.H., 1978, Zinc binding in human duodenal secretions, Lancet 2: 423.Google Scholar
  22. Casey, C.E., Walravens, P.A., and Hambidge, K.M., 1981, Availability of zinc: loading tests with human milk, cow’s milk, and infant formulas, Pediatrics 68: 394.Google Scholar
  23. Cavell, P.A., and Widdowson, E.M., 1964, Intakes and excretions of iron, copper and zinc in the neonatal period, Arch. Dis. Child 39: 496.Google Scholar
  24. Chandra, R.K., 1980, Acrodermatitis enteropathica: zinc levels and cell-mediated immunity, Pediatrics 66: 789.Google Scholar
  25. Chvapil, M., 1973, New aspects in the biological role of zinc: a stabilizer of macromolecules and biological membranes, Life Sci. 13: 1041.Google Scholar
  26. Cikrt, M., 1973, Enterohepatic circulation of 64Cu, 52Mn, and 203Hg in rats, Arch. Toxicol. 31: 51.Google Scholar
  27. Cikrt, M., Havrdova, J., and Tichy, M., 1974, Changes in the binding of copper and zinc in the rat bile during 24 hours after application, Arch. Toxicol 32: 321.Google Scholar
  28. Cotzias, G.C., Bong, C., and Selleck, B., 1962, Specificity of zinc pathway through the body: turnover of 65Zn in the mouse, Am. J. Physiol 202: 359.Google Scholar
  29. Cousins, R.J., 1979a, Regulation of zinc absorption: role of intracellular ligands, Am. J. Clin. Nutr 32: 339.Google Scholar
  30. Cousins, R.J., 1979b, Regulatory aspects of zinc metabolism in liver and intestine, Nutr. Rev 37: 97.Google Scholar
  31. Cousins, R.J., Smith, K.T., Failla, M.L., and Markowitz, L.A., 1978, Origin of low molecular weight zinc binding ligands in rat intestine, Life Sci. 23: 1819.Google Scholar
  32. Danbolt, N., and Closs, K., 1943, Acrodermatitis enteropathica, Acta Derm. Venereol 23: 127.Google Scholar
  33. Danks, D.M., Camakaris, J., and Stevens, B.J., 1978, The cellular defect in Menkes’ syndrome and in mottled mice, in: Trace Element Metabolism in Man and Animals — 3( M. Kirchgessner, ed.), pp. 401 - 404, Technische Universitat Munchen, Freising-Weihenstephan.Google Scholar
  34. Dauncey, M.J., Shaw, J.C.L., and Urman, J., 1977, The absorption and retention of magnesium, zinc and copper by low birth weight infants fed pasteurized breast milk, Pediatr. Res 11: 911.Google Scholar
  35. Dickie, M.M., 1969, Lethal-milk: a new mutation in the mouse, Mouse News Letter 41: 30.Google Scholar
  36. Dillaha, C.J., Lorincz, A.L., and Aavik, O.R., 1953, Acrodermatitis enteropathica. Review of the literature and report of a case successfully treated with diodoquin, J. Am. Med. Assn 152: 509.Google Scholar
  37. Dreosti, I.E., and Hurley, L.S., 1975, Depressed thymidine kinase activity in zinc-deficient rat embryos, Proc. Soc. Exp. Biol. Med 150: 161.Google Scholar
  38. Dreosti, I.E., Grey, P.C., and Wilkins, P.J., 1972, Deoxyribonucleic acid synthesis protein synthesis and teratogenesis in zinc-deficient rats, S. Afr. Med. J 46: 1585.Google Scholar
  39. Duncan, J.R, and Hurley, L.S., 1978, Intestinal absorption of zinc: a role for a zinc binding ligand in milk, Am. J. Physiol 235: E556.Google Scholar
  40. Dungan, D.D., Keen, C.L., Lönnerdal, B., and Hurley, L.S., 1980, Developmental changes in concentrations of iron, copper and zinc in mouse and rat tissues, Fed. Proc 39: 903.Google Scholar
  41. Eckhert, C.D., and Hurley, L.S., 1977, Reduced DNA synthesis in zinc deficiency: regional differences in embryonic rats, J. Nutr 107: 855.Google Scholar
  42. Eckhert, C.D., Sloan, M.V., Duncan, J.R., and Hurley, L.S., 1977, Zinc binding: a difference between human and bovine milk, Science 195: 789.Google Scholar
  43. Eichhorn, G.L., Berger, N.A., Butsow, J.J., Clark, P., Hein, J., Pitha, I., Richardson, C., Rifkind, R.M., Shin, Y., and Tarien, E., 1973, in: Metal Ions in Biologial Systems(S.K. Dhar, ed.), p. 43, Springer Science+Business Media New York.Google Scholar
  44. Elmes, M.E., 1976, The Paneth cell population of the small intestine of the rat—effects of fasting and zinc deficiency on total count and on dithizone-reactive count, J. Path 118: 183.Google Scholar
  45. Entwisle, B.R., 1965, Acrodermatitis enteropathica. Report of a case in a twin with dramatic response to expressed human milk, Austral. J. Derm 8: 13.Google Scholar
  46. Erway, L.C., Piletz, J.E., and Ganschow, R.E., 1979, Zinc supplementation prevents mortality in lethal-milk mice, Mouse News Letter 60: 41.Google Scholar
  47. Evans, G. W., 1980, Normal and abnormal zinc absorption in man and animals: the trypto-phan connection, Nutr. Rev 38: 137.Google Scholar
  48. Evans, G.W., and Johnson, P.E., 1977, Defective prostaglandin synthesis in acrodermatitis enteropathica, Lancet 1: 52.Google Scholar
  49. Evans, G.W., and Johnson, E.C., 1980a, Zinc concentration of liver and kidneys from rat pups nursing dams fed supplemental zinc dipicolinate or zinc acetate, J. Nutr 110: 2121.Google Scholar
  50. Evans, G.W., and Johnson, P.E., 1980b, Characterization and quantitation of a zinc binding ligand in human milk, Pediatr. Res 14: 876.Google Scholar
  51. Evans, G.W., Majors, P.F., and Cornatzer, W.E., 1970, Mechanism of cadmium and zinc antagonism of copper metabolism, Biochem. Biophys. Res. Commun 40: 1142.Google Scholar
  52. Evans, G.W., Grace, C.I., and Votava, H.J., 1975, A proposed mechanism for zinc absorption in the rat, Am. J. Physiol 228: 501.Google Scholar
  53. Evans, G.W., Johnson, E.C., and Johnson, P.E., 1979a, Zinc absorption in the rat determined by radioisotope dilution, J. Nutr 109: 1258.Google Scholar
  54. Evans, G.W., Johnson, P.E., Brushmiller, J.G., and Ames, R.W., 1979b, Detection of labile zinc binding ligands in biological fluids by modified gel filtration chromatography, Anal. Chem 51: 839.Google Scholar
  55. Feldman, B.F., 1981, Anemias associated with blood loss and hemolysis, Vet. Clin. North America: Small Animal Practice 11: 265.Google Scholar
  56. Flagstad, T., 1976, Lethal trait A46 in cattle, Nord. Vet.-Med 28: 160.Google Scholar
  57. Flagstad, T., 1977, Intestinal absorption of 65zinc in A46 (Adema disease) after treatment with oxychinolines, Nord. Vet.-Med 29: 96.Google Scholar
  58. Flagstad, T., 1981, Zinc absorption in cattle with a dietary picolinic acid supplement, J. Nutr 40: 65.Google Scholar
  59. Fomon, S.J., 1974, in: Infant Nutrition, pp. 370-371, W.B. Saunders Co., Philadelphia.Google Scholar
  60. Freier, S., Faber, J., Goldstein, R., and Mayer, M., 1973, Treatment of acrodermatitis enteropathica by intravenous amino acid hydrolysate, J. Pediatr 82: 109.Google Scholar
  61. Garretts, M., and Molokhia, M., 1977, Acrodermatitis enteropathica without hypozincemia, J. Pediatr 91: 492.Google Scholar
  62. Giroux, E., and Prakash, N.J., 1977, Influence of zinc-ligand mixtures on serum zinc levels in rats, J. Pharm. Sci 66: 391.Google Scholar
  63. Graves, K., Kestenbaum, T., and Kalivas, J., 1980, Hereditary acrodermatitis enteropathica in an adult, Arch. Dermatol 116: 562.Google Scholar
  64. Green, M.C., and Sweet, H.O., 1973, The Jackson Laboratory—Linkages and Chromosomes, Mouse News Letter 48: 35.Google Scholar
  65. Gronborg-Pedersen, H., 1970, Morbus ademae, Medlemsbl. Danske Dyrlaege førening, 53: 143.Google Scholar
  66. Hahn, C.J., and Evans, G.W., 1973, Identification of a low molecular weight 65Zn complex in rat intestine, Proc. Soc. Exp. Biol. Med 144: 793.Google Scholar
  67. Hambidge, K.M., Hambidge, C., Jacobs, M., and Baum, J.D., 1972, Low levels of zinc in hair, anorexia, poor growth and hypogeusia in children, Pediatr. Res 6: 868.Google Scholar
  68. Hambidge, K.M., Walravens, P.A., Brown, R.M., Webster, J., White, S., Anthony, M., and Roth, M.L., 1976, Zinc nutrition of preschool children in the Denver Head Start program, Am. J. Clin. Nutr 29: 734.Google Scholar
  69. Hambidge, K.M., Walravens, P.A., Casey, C.E., Brown, R.M., and Bender, C., 1979, Plasma zinc concentrations of breast-fed infants, J. Pediatr 94: 607.Google Scholar
  70. Hambraeus, L., 1977, Proprietary milk versus human breast milk in infant feeding, Pediatr. Clin. N. Amer 24: 17.Google Scholar
  71. Harvey, J.W., 1980, Canine hemolytic anemias, J. Am. Vet. Med. Assoc 176: 970.Google Scholar
  72. Henderson, L.M., and Swan, P.B., 1971, Picolinic acid carboxylase, in: Methods in EnzymologyVol. 18B ( D.B. McCormick and L.D. Wright, eds.), pp. 175 - 180, Academic Press, New York.Google Scholar
  73. Henkin, R.I., Schulman, J.D., Schulman, C.B., and Bronzert, D.A., 1973, Changes in total, nondiffusible and diffusible plasma zinc and copper during infancy, J. Pediatr 82: 831.Google Scholar
  74. Hirsch, F.S., Michel, B., and Strain, W.H., 1976, Gluconate zinc in acrodermatitis entero-pathica, Arch. Dermatol 112: 475.Google Scholar
  75. Hoag, G.W., Brown, R.G., Smart, M.E., and Subden, R.E., 1976a, Alaskan malamute chondrodysplasia. I. Bone composition studies, Growth 40: 3.Google Scholar
  76. Hoag, G.W., Brown, R.G., Smart, M.E., and Subden, R.E., 1976b, Alaskan malamute chondrodysplasia. II. Urinary excretion of hydroxyproline, uronic acid and acid mucopolysaccharides, Growth 40: 13.Google Scholar
  77. Hurley, L.S., 1976, Interaction of genes and metals in development, Fed. Proc 35: 2271.Google Scholar
  78. Hurley, L.S., 1980, in: Developmental Nutrition, 335 pp., Prentice Hall, Englewood Cliffs, NJ.Google Scholar
  79. Hurley, L.S., and Lönnerdal, B., 1980, Tryptophan, picolinic acid and zinc absorption: an unconvincing case, J. Nutr 110: 2536.Google Scholar
  80. Hurley, L.S., and Lönnerdal, B., 1981, Picolinic acid as a zinc-binding ligand in human milk: an unconvincing case, Pediatr. Res 15: 166.Google Scholar
  81. Hurley, L.S., and Lönnerdal, B., 1982, Zinc binding in human milk: citrate versus picolinate, Nutr. Rev 40: 65.Google Scholar
  82. Hurley, L.S., Eckhert, C.D., Duncan, J.R., and Sloan, M.V., 1977a, Acrodermatitis entero-pathica and human breast milk, Lancet 1: 195.Google Scholar
  83. Hurley, L.S., Duncan, J.R., Sloan, M.V., and Eckhert, C.D., 1977b, Zinc-binding ligands in milk and intestine: A role in neonatal nutrition? Proc. Nat. Acad. Sci. USA 74: 3547.Google Scholar
  84. Hurley, L.S., Keen, C.L., Young, H.M., and Lönnerdal, B., 1982, Effect of chelates on zinc-concentration in rat maternal and pup tissues, Fed. Proc 41: 781.Google Scholar
  85. Jackson, M.J., 1977, Zinc and diodohydroxyquinoline therapy in acrodermatitis enteropathica, J. Clin. Pathol 30: 284.Google Scholar
  86. Jackson, M.J. Jones, D.A., and Edwards, R.H.T., 1981, Zinc absorption in the rat, Br. J. Nutr 46: 15.Google Scholar
  87. Jameson, S., 1976, Effects of zinc deficiency in human reproduction, Acta Med. Scand. Suppl. 593.Google Scholar
  88. Jameson, S., 1981, Zinc nutrition and pregnancy in humans, in: Fourth International Symposium on Trace Elements in Man and Animals(TEMA-4) ( J. McHowell, J.M. Gawthorne, and C.L. White, eds.), pp. 243 - 248, Griffin Press Ltd., Netley, South Australia.Google Scholar
  89. Jenness, R., 1974, The composition of milk: salts, in: LactationVol. III. ( B.L. Larson and V.R. Smiths, eds.), pp. 43 - 44, Academic Press, New York and London.Google Scholar
  90. Johnson, P.E., and Evans, G.W., 1978a, Identification of a prostaglandin E2-zinc complex in human breast milk, and porcine and rat duodenum, Fed. Proc 37: 889.Google Scholar
  91. Johnson, P.E., and Evans, G.W., 1978b, Relative zinc availability in human breast milk, infant formulas, and cow’s milk, Am. J. Clin. Nutr 31: 416.Google Scholar
  92. Käi, J.H.R., and Vallee, B.L., 1960, Metallothionein: a cadmium and zinc containing protein from equine renal cortex, J. Biol. Chem 235: 3460.Google Scholar
  93. Katoh, T., Igarashi, M., Okhashi, E., Ohi, R., Hebiguchi, T., and Seiji, M., 1976, Acroder-matitis enteropathica-like eruption association with parenteral nutrition, Dermatologica 152: 119.Google Scholar
  94. Keen, C.L., and Hurley, L.S., 1980, Developmental changes in concentrations of iron, copper, and zinc in mouse tissues, Mech. Ageing Dev 13: 161.Google Scholar
  95. Keen, C.L., Lönnerdal, B., and Hurley, L.S., 1981, Developmental changes in zinc and copper in mouse and rat tissues, in: Fourth International Symposium on Trace Elements in Man and Animals(TEMA-4) ( J. McHowell, J.B. Gawthorne, and C.L. White, eds.), pp. 287 - 290, Griffin Press Ltd., Netley, South Australia.Google Scholar
  96. Kowarski, S., Blair-Stanek, C.S., and Schachter, D., 1974, Active transport of zinc and identification of zinc binding protein in rat jejunal mucosa, Am. J. Physiol 226: 401.Google Scholar
  97. Krieger, I., 1980, Picolinic acid in the treatment of disorders requiring zinc supplementation, Nutr. Rev 38: 148.Google Scholar
  98. Krieger, I., and Evans, G.W., 1980, Acrodermatitis enteropathica without hypozincemia. Therapeutic effect of a pancreatic enzyme preparation due to a zinc binding ligand, J. Pediatr 96: 32.Google Scholar
  99. Kroneman, J., Mey, G.J.W. van der, and Helder, A., 1975, Hereditary zinc deficiency in Dutch Friesian cattle, Zbl. Yet. Med. A 22: 201.Google Scholar
  100. Lombeck, I., Von Bassewitz, D.B., Becker, K., Tinschmann, P., and Kastner, H., 1974, Ultrastructural findings on acrodermatitis enteropathica, Pediatr. Res 8: 82.Google Scholar
  101. Lombeck, I., Schnippering, H.G., Ritzl, F., Feiendegen, L.E., and Bremer, H.J., 1975, Absorption of zinc in acrodermatitis enteropathica, Lancet 1: 855.Google Scholar
  102. Lönnerdal, B., and Fransson, G.B., 1981, Distribution of copper, zinc, calcium and magnesium in human milk, in: Nutrition in Health and Disease and International Development: symposia from the 12th International Congress of Nutrition (A.E. Harper and G.K. Davis, eds.), no. 220, Liss, New York.Google Scholar
  103. Lönnerdal, B., and Hoffman, B., 1981, Alkaline reduction of dextran gels and cross-linked agarose to overcome nonspecific binding of trace elements, Biol. Trace Element Res 3: 301.Google Scholar
  104. Lönnerdal, B., Stanislowski, A.G., and Hurley, L.S., 1980a, Isolation of a low molecular weight zinc binding ligand from human milk, J. Inorg. Biochem 12: 71.Google Scholar
  105. Lönnerdal, B., Keen, C.L., Sloan, M.V., and Hurley, L.S., 1980b, Molecular localization of zinc in rat milk and neonatal intestine, J. Nutr 110: 2414.Google Scholar
  106. Lönnerdal, B., Schneeman, B.O., Keen, C.L., and Hurley, L.S., 1980c, Molecular distribution of zinc in biliary and pancreatic secretions, Biol. Trace Element Res 2: 149.Google Scholar
  107. Lönnerdal, B., Keen, C.L., and Hurley, L.S., 1981a, Iron, copper, zinc and manganese in milk, Ann. Rev. Nutr 1: 149.Google Scholar
  108. Lönnerdal, B., Keen, C.L., and Hurley, L.S., 1981b, Trace elements in milk from various species in: Fourth International Symposium on Trace Elements in Man and Animals(TEMA-4) (J. McHowell, J.M. Gawthorne, and C.L. White, eds.), pp. 249-252, Griffin Press, Netley, South Australia.Google Scholar
  109. Lönnerdal, B., Keen, C.L., and Hurley, L.S., 1981b, Trace elements in milk from various species in: Fourth International Symposium on Trace Elements in Man and Animals(TEMA-4) (J. McHowell, J.M. Gawthorne, and C.L. White, eds.), pp. 249-252, Griffin Press, Netley, South Australia.Google Scholar
  110. Luckey, T.D., Mende, T.J., and Pleasants, J., 1954, The physical and chemical characterization of rat’s milk, J. Nutr 54: 345.Google Scholar
  111. MacDonald, L., and Gibson, R.S., 1981, The zinc status of breast and formula fed infants, in: Fourth International Symposium on Trace Elements in Man and Animals(TEMA-4) ( J. McHowell, J.M. Gawthorne, and C.L. White, eds.), pp. 121 - 124, Griffin Press Ltd., Netley, South Australia.Google Scholar
  112. Martin, M.T., Licklider, K.F., Brushmiller, J.G., and Jacobs, F.A., 1981, Detection of low molecular weight copper (II) and zinc (II) binding ligands in ultrafiltered milks—the citrate connection, J. Inorg. Biochem 15: 55.Google Scholar
  113. McClain, P.E., Wiley, E.R., Beecher, R.G., Anthony, W.L., and Hsu, J.M., 1973, Influence of zinc deficiency on synthesis and crosslinking of rat skin collagen, Biochem. Biophys. Acta 304: 45.Google Scholar
  114. McMaster, D., Steel, L., and Love, A.H.G., 1981, Zinc absorption by vascularly perfused small intestine, in: Fourth International Symposium on Trace Elements in Man and Animals(TEMA-4) ( J. McHowell, J.M. Gawthorne, and C.L. White, eds.), pp. 121 - 124, Griffin Press Ltd., Netley, South Australia.Google Scholar
  115. McPherson, E.A., Beattie, I.S., and Young, G.B., 1964, An inherited defect in Friesian calves, Nord. Vet. Med. Suppl 1: 533.Google Scholar
  116. Menard, M.P., and Cousins, R.J., 1982, Zinc transport by isolated brush border membrane vehicles from rat intestine, Fed. Proc 41: 779.Google Scholar
  117. Methfessel, A.H., and Spencer, H., 1973, Zinc metabolism in the rat. I. Intestinal absorption of zinc, J. Appl. Physiol 34: 58.Google Scholar
  118. Michäelsson, G., 1974, Zinc therapy in acrodermatitis enteropathica, Acta Dermatovener. (Stockholm) 54: 377.Google Scholar
  119. Miller, W.J., 1969, Absorption, tissue distribution, endogenous excretion, and homeostatic control of zinc in ruminants, Am. J. Clin. Nutr 22: 1323.Google Scholar
  120. Morishima, T., Yaji, S., and Takemura, T., 1981, An acquired form of acrodermatitis ente-ropathica due to long-term lactose-free milk alimentation, in: Fourth International Symposium on Trace Element Metabolism in Man and Animals(TEMA-4) ( J. McHowell, J.M. Gawthorne, and C.L. White, eds.), pp. 487 - 490, Griffin Press Ltd., Netley, South Australia.Google Scholar
  121. Moynahan, E.J., 1966, Acrodermatitis enteropathica with secondary lactose intolerance, and tertiary deficiency state, probably due to chelation of essential nutrients by di-iodohydroxyquinoline, Proc. Roy. Soc. Med 59: 445.Google Scholar
  122. Moynahan, E.J., 1974, Acrodermatitis enteropathica: a lethal inherited human zinc-deficiency disorder, Lancet 2: 399.Google Scholar
  123. Moynahan, E.J., and Barnes, P.M., 1973, Zinc deficiency and a synthetic diet for lactose intolerance, Lancet 1: 676.Google Scholar
  124. Mutch, P.B., and Hurley, L.S., 1974, Effect of zinc deficiency during lactation on postnatal growth and development, J. Nutr 104: 828.Google Scholar
  125. Mutch, P.B., and Hurley, L.S., 1980, Mammary gland function and development: effect of zinc deficiency in rat, J. Physiol 238: E26.Google Scholar
  126. Neldner, K.H., and Hambidge, K.M., 1975, Zinc therapy of acrodermatitis enteropathica, N. Engl. J. Med 292: 879.Google Scholar
  127. Nishimura, H., 1953, Zinc deficiency in suckling mice deprived of colostrum, J. Nutr 49: 79.Google Scholar
  128. O’Dell, B.L., 1981, Metabolic functions of zinc—a new look, in: Fourth International Symposium on Trace Elements in Man and Animals(TEMA-4) ( J. McHowell, J.M. Gawthorne, and C.L. White, eds.), Griffin Press Ltd., Netley, South Australia.Google Scholar
  129. Ohlsson, A., 1981, Case Report: acrodermatitis enteropathica: reversibility of cerebral atrophy with zinc therapy, Acta. Paediatr. Scand 70: 269.Google Scholar
  130. Ohtake, M., 1977, Serum zinc and copper levels in healthy Japanese infants, Tohoku J. Exp. Med 123: 265.Google Scholar
  131. Ølholm-Larsen, P., 1978, Untreated acrodermatitis enteropathica in adults, Dermatologica 156: 155.Google Scholar
  132. Ølholm-Larsen, P., 1979, Serum zinc levels in heterozygous carriers of the gene for acrodermatitis enterovathica, Hum. Genet 46: 65.Google Scholar
  133. Parisi, A.F., and Vallee, B.L., 1969, Zinc metalloenzymes: characteristics and significance in biology and medicine, Am. J. Clin. Nutr 22: 1222.Google Scholar
  134. Piletz, J. E., and Ganschow, R. E., 1978a, Zinc deficiency in murine milk underlies expression of the lethal milk (lm) mutation, Science 199: 181.Google Scholar
  135. Piletz, J.E., and Ganschow, R.E., 1978b, Lethal-milk mutation results in dietary zinc deficiency in nursing mice, Am. J. Clin. Nutr 31: 560.Google Scholar
  136. Pories, W.J., Henzel, J.H., Rob, G.G., and Strain, W.H., 1976, Acceleration of wound healing in man with zinc sulfate given by mouth, Lancet 1: 121.Google Scholar
  137. Portnoy, B., and Molokhia, M., 1974, Zinc in acrodermatitis enteropathica, Lancet 2: 663.Google Scholar
  138. Prasad, A.S., 1976, in: Trace Elements in Human Health and Disease, Academic Press, New York.Google Scholar
  139. Rebello, T., Lönnerdal, B., and Hurley, L.S., 1982, Picolinic acid in milk, pancreatic juice and intestine: inadequate for role in zinc absorption, Am. J. Clin. Nutr 35: 1.Google Scholar
  140. Richards, M.P., and Cousins, R.J., 1976, Zinc binding protein: relationship to short-term changes in zinc metabolism, Proc. Soc. Exp. Biol. Med 153: 52.Google Scholar
  141. Richards, M.P., and Cousins, R.J., 1977, Isolation of an intestinal metallothionein induced by parenteral zinc, Biochem. Biophys. Res. Commun 75: 286.Google Scholar
  142. Roberts, J.A.F., 1970, in: An Introduction to Medical Genetics, Oxford University Press, London.Google Scholar
  143. Robertson, A.F., and Sotos, J., 1975, Treatment of acrodermatitis enteropathica with zinc sulfate, Pediatrics 55: 738.Google Scholar
  144. Rodin, A.E., and Goldman, A.S., 1969, Autopsy findings in acrodermatitis enteropathica, J. Am. Clin. Path 51: 315.Google Scholar
  145. Schricker, B.R., and Forbes, R.M., 1978, Studies on the chemical nature of a low molecular weight zinc binding ligand in rat intestine, Nutr. Rep. Int 18: 159.Google Scholar
  146. Siegel, H., and McCormick, D.B., 1970, On the discriminating behavior of metal ions and ligands with regard to their biological significance, Acc. Chem. Res 3: 201.Google Scholar
  147. Smart, M.E., and Fletch, S., 1971, A hereditary growth defect in purebred Alaskan malamutes, Can. Yet. J 12: 31.Google Scholar
  148. Sobel, A.E., Goldenberg, M., and Schmerzler, E., 1954, Calcification. XI. Studies on the incorporation of citrate in calcification in vitro, J. Dent. Res. 33: 492.Google Scholar
  149. Song, M.K., and Adham, N.F., 1978, Role of prostaglandin E2 in zinc absorption in the rat, Am. J. Physiol 234: E99.Google Scholar
  150. Song, M.K., and Adham,N.F., 1979, Evidence for an important role of prostaglandins E2 and F2 in the regulation of zinc transport in the rat, J. Nutr 109: 2152.Google Scholar
  151. Starcher, B.C., 1969, Studies on the mechanism of copper absorption, J. Nutr 97: 321.Google Scholar
  152. Stober, M., 1971, Parakeratose beim schwarzbunten Niederungskalb. I. Klinisches Bild and Atiologie, Dtsch. Tierartztl. Wschr 78: 257.Google Scholar
  153. Sunderman, F.W., Jr., 1975, Current status of zinc deficiency in the pathogenesis of neurological, dermatological and musculoskeletal disorders, Ann. Clin. Lab. Sci 5: 132.Google Scholar
  154. Thunberg, T., 1953, Occurrence and significance of citric acid in the animal organism, Physiol. Rev 33: 1.Google Scholar
  155. Underwood, E.J., 1977, in: Trace Elements in Human and Animal Nutrition, pp. 545, Aca-demic Press, New York.Google Scholar
  156. Van Campen, D.R., and Kowalski, T.J., 1971, Studies on zinc absorption: 65Zn binding by homogenates of rat intestinal mucosa, Proc. Soc. Exp. Biol. Med 136: 294.Google Scholar
  157. Vohra, P., and Kratzer, F.H., 1966, Influence of various phosphates and other complexing agents on the availability of zinc for turkey poults, J. Nutr 89: 106.Google Scholar
  158. Walravens, P.A., and Hambidge, K.M., 1976, Growth of infants fed a zinc supplemented formula, Am. J. Clin. Nutr 29: 1114.Google Scholar
  159. Walravens, P.A., Hambidge, K.M., Neldner, K.H., Silverman, A., Van Doorninck, W.J., Mierau, G., and Favara, B., 1978, Zinc metabolism in acrodermatitis enteropathica, J. Pediatr 93: 71.Google Scholar
  160. Wapnir, R.A., Wang, J. Exeni, R.A., and McVicar, M., 1981, Experimental evaluation of ligands for the intestinal absorption of zinc in vivo, Am. J. Clin. Nutr 34: 651.Google Scholar
  161. Weigand, E., and Kirchgessner, M., 1976a, Radioisotope dilution technique for determination of zinc absorption in vivo, Nutr. Metab. 20: 307.Google Scholar
  162. Weigand, E., and Kirchgessner, M., 1976b, 65Zn-labeled tissue zinc for determination of endogenous fecal zinc excretion in growing rats, Nutr. Metabol. 20:314.Google Scholar
  163. Weigand, E., and Kirchgessner, M., 1980, Total true efficiency of zinc utilization: determination and homeostatic dependence upon the zinc supply status in young rats, J. Nutr 110: 469.Google Scholar
  164. Weismann, K., and Flagstad, T., 1976, Hereditary zinc deficiency (Adema disease) in cattle, and animal parallel to acrodermatitis enteropathica, Acta Dermatovener. (Stockholm) 56: 151.Google Scholar
  165. Weismann, K. Hjorth, N., and Fischer, A., 1976, Zinc depletion syndrome with acrodermatitis during long-term intravenous feeding, Clin. Exp. Dermatol 1: 237.Google Scholar
  166. Wilson, I.D., McClain, C.J., and Erlandsen, S.L., 1980, Ileal paneth cells and IgA system in rats with severe zinc deficiency: an immunohistochemical and morphological study, Histochemical J. 12: 457.Google Scholar
  167. Yoza, N., 1977, Determining the stability constant of a metal complex by gel chromatogram-phy, J. Chem. Ed 54: 284.Google Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Bo Lönnerdal
    • 1
  • Carl L. Keen
    • 1
  • Lucille S. Hurley
    • 1
  1. 1.Department of NutritionUniversity of CaliforniaDavisUSA

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