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Zinc is an essential trace element in human nutrition and its deficiency is a world nutritional problem. However, the zinc content of foods is low and its availability is conditioned by several physiologic and dietary factors. For that reason, the objective of the present work is to compile past and present information about the influence of these factors on zinc availability to try to improve this availability.

Zinc metabolism is controlled within relatively restricted limits throughout the life cycle. Expression and localization of zinc transporters 1, 2 and 4 during pregnancy and lactation in small intestine, mammary gland and liver of the rat were investigated using Northern analysis, Western blotting and immunohistochemistry. In maternal tissues, zinc transporter 4 was the most widely expressed among these zinc transporters in the tissues examined. In small intestine and liver, zinc transporter 4 increased from levels found during late gestation, but zinc transporter 1 did not. Zinc transporter 2 expression in small intestine was transient, being highest around parturition, and was not detected in liver. Immunohistochemistry revealed unique patterns of zinc transporter localization at different stages of development. In the placenta, zinc transporters 1 and 4 were found concentrated along the villous visceral splanchnopleure. In the mammary gland, zinc transporter 4 was most abundant in cells surrounding the alveolar ducts and oriented to the basement lamina. All three transporters were highly expressed in neonatal small intestine, principally near the apical surface, but zinc transporters 1 and 4 increased in abundance at the basolateral surface during development. Zinc transporter 2 was oriented apically, directly adjacent to the microvilli of enterocytes. Within the intestine, expression of each transporter was limited to enterocytes. These results support a role for these transporters in maintaining an adequate zinc supply derived from the maternal diet for zinc acquisition and use by the fetus and neonate. J. Nutr. 133: 342-351, 2003. KEY WORDS: * transport * fetal development * lactation * gene expression

Deficient intake of zinc from the diet upregulates both uroguanylin (UG) and inducible nitric oxide synthase (iNOS) expression in rats. Because these changes influence intestinal fluid secretion and intestinal cell pathophysiology, they relate to the incidence of diarrheal disease and its reversal by zinc as well as intestinal inflammation in general. A model of moderate zinc deficiency in rats, which changes molecular indices of zinc deficiency, was used to further explore the effects of the proinflammatory cytokine interleukin (IL)-1[alpha] and zinc repletion on these changes. IL-1[alpha] has been shown to have a role in the intestinal inflammation that occurs with bacterial infection. Our results showed a permissive effect of zinc deficiency on both UG and iNOS expression. Specifically, UG expression was responsive to zinc deficiency and IL-1[alpha] challenge, which were additive when combined, whereas iNOS expression was upregulated by IL-1[alpha] only during the deficiency. Immunohistochemistry showed that the increase in UG was limited to enterocytes of the upper villus but, in contrast, the increase in iNOS was principally in cells of the lamina propria of IL-1[alpha]-treated rats. Cells exhibiting UG upregulation did not co-express serotonin. Repletion with zinc reversed upregulation of the iNOS gene within 1 d, whereas UG upregulation required 3-4 d to return to normal. This differential response to repletion suggests that mechanisms of UG and iNOS dysregulation are different. Dysregulation of both genes may contribute to the severity of zinc-responsive diarrheal disease and intestinal inflammatory disease. KEY WORDS: * zinc deficiency * diarrheal disease * interleukin 1 * inflammation * gene regulation * rats

Herein, the function of pancreatic metallothionein (MT)-I during zinc deficiency in pregnancy was examined using transgenic mice, which constitutively express the mouse MT-I gene driven by the rat elastase I promoter. Pancreatic MT protein levels and zinc levels were elevated significantly in the transgenic mice compared with those in control mice. Pregnant transgenic and control mice were fed zinc-deficient (1 [micro]g/g beginning at d 8) or zinc-adequate (50 [micro]g/g) diets during pregnancy, and the effects on the morphology of embryos were determined at d 14 of pregnancy (d 1 = vaginal plug). As other indicators of zinc deficiency, maternal pancreatic MT levels, as well as the expression of zinc-regulated genes in the embryonic visceral yolk sac were examined. Under these experimental conditions of moderate dietary zinc deficiency, 21.3% of the embryos in control mice exhibited morphological defects, whereas only 5.8% of the embryos in the elastase-MT-I transgenic females had developed abnormally by d 14. Surprisingly, dietary zinc deficiency caused a >95% decrease in pancreatic MT protein concentration in these transgenic mice. This suggests the post-transcriptional control of MT protein levels during zinc deficiency because the rat elastase I promoter is not metal-regulated. The decrease in pancreatic MT protein levels was paralleled by a dramatic decrease in the relative abundance of MT-I mRNA and a dramatic increase in the relative abundance of the zinc/iron regulated transporter-related zinc transporter-4 (ZIP4) mRNA in the embryonic visceral yolk sac. Thus, the constitutive overexpression of pancreatic MT-I in these mice attenuated, but did not prevent the effects of maternal or embryonic zinc deficiency under these conditions. Overall, these findings are consistent with the hypothesis that mouse pancreatic MT-I may participate in providing a labile pool of maternal zinc for the developing embryo during periods of zinc deficiency. KEY WORDS: * mice * metallothionein * pregnancy * transgenic * pancreas * zinc homeostasis

An integration of knowledge concerning regulation of metallothionein expression with research on metallothionein's proposed functions is necessary to delineate how this metalloprotein affects cellular processes, especially zinc metabolism. Metallothionein expression is driven by a number of physiological mediators through several response elements in the metallothionein gene promoter. Cellular accumulation of metallothionein depends on both gene expression and protein degradation. Both depend largely on availability of cellular zinc derived from the dietary zinc supply. Metallothionein expression is related to zinc accumulation in certain organs. Evidence has been produced, which suggests that metallothionein could act in a number of biochemical processes. It may act in zinc trafficking and/or zinc donation to apoproteins, including zinc finger proteins that act in cellular signaling and transcriptional regulation. As a result, metallothionein expression may affect a number of cellular processes including gene expression, apoptosis, proliferation and differentiation. The ability of metallothionein to exchange other metals with zinc in these proteins may explain a role in metal toxicity. Similarly, mobilization of zinc from metallothionein by oxidative stresses may explain its proposed antioxidant function. Apparent good health of metallothionein-deficient mice argues against a critical biological role for metallothionein; however, expression may be critical in times of stress. J. Nutr. 130: 1085-1088, 2000. KEY WORDS: * zinc * metallothionein * gene expression

The influence of zinc status on the levels of p53, as well as downstream targets of p53 in cell repair and survival, was examined in human aortic endothelial cells (HAECs). A serum-reduced low-zinc medium (ZD) was used to deplete zinc over one passage. Other treatments included zinc-normal control (ZN), zinc-adequate (ZA), and zinc-supplemented (ZS) treatment with 3.0, 16.0, and 32.0 [micro] M zinc, respectively. Cellular zinc levels in the ZD cells were 64% of ZN controls; levels in the ZA cells were not different, but levels in ZS cells were significantly higher (40%) than in ZN cells. No difference in p53 mRNA abundance was detected among all treatments; however, p53 nuclear protein levels were >100% higher in the ZD and ZS cells and almost 200% higher in the ZA cells than in ZN controls. In addition, p21 mRNA abundance, a downstream target of p53 protein, was increased in the ZS ceils compared with both the ZN control and ZD cells. In the ZS cells, bax and mcl-1 were also ~50% higher compared with ZN controls, whereas bcl-2 mRNA was increased compared with ZA cells. Moreover, caspase-3 activity of ZD cells was not different from that of ZN controls but was reduced to 83 and 69% of ZN controls in ZA and ZS cells, respectively. Thus p53 protein and p53 downstream target genes appeared to be modulated by intracellular zinc status in HAECs. p53 tumor suppressor gene; apoptosis; zinc depleted; zinc supplemented; atherosclerosis

The main objective of this study was to describe Holstein neonatal growth and development as influenced by dietary zinc supplementation and the CD18 genotype, both of which may affect immune competence. Holstein calves (n = 421), after being fed colostrum, were brought to a calf facility, randomly assigned to one of four zinc supplementation groups (control at 40 mg Zn/kg DM or the control diet supplemented with an additional 60 mg Zn/kg DM provided as either zinc sulfate, zinc lysine, or zinc methionine), weighed, and measured for morphometric growth parameters. Measurements were repeated at 30, 60, and 90 d. Calves were also genotyped for the presence of the mutant D128G CD18 allele, which, if present in two copies, causes bovine leukocyte adhesion deficiency. Zinc supplementation above 40 mg Zn/kg DM, regardless of the chemical form, did not accelerate growth (P > 0.25). Further, overall calf growth performance was not suppressed or improved (P > 0.4) in calves heterozygous at the CD18 locus relative to calves homozygous for the normal CD18 allele, although genotype negatively affected some morphometric measurements (P < 0.05). Using these data, quadratic models of early growth were generated as a preliminary step to develop growth criteria that will allow producers, veterinarians, and animal scientists to identify poor growth performance early in neonatal life. Such criteria provide the basis for tools to improve economic performance. Key Words: Calves, Cattle Diseases, Growth, Zinc

Zinc deficiency leads to pathological signs that are related to impaired function of plasma membrane proteins. The purpose of this study was to assess the effect of dietary zinc status on the sulfhydryl (SH) content of erythrocyte plasma membranes and erythrocyte function. Three experiments were performed. In the first, immature male rats were fed for 21 d either a low-zinc ( KEY WORDS: zinc status; osmotic fragility; sulfhydryl concentration; band 3; zinc binding; rats

Zinc uptake in intestinal and renal brush-order membrane vesicles (BBMV) was studied to determine the effect of thyroid hormones on zinc metabolism. Results indicate that thyroid hormones regulate the zinc transport activity in both the intestinal and renal BBMV. It was also observed that the thyroid hormone exerts cellular effects and alters the the lipid composition of the rat colonic plasma membrane.

The influence of metallothionein (MT) on Zn transfer into non-gut tissues was investigated in MT-null (MT-/-) and normal (MT+/+) mice 4 h after oral gavage of aqueous 65ZnS[O.sub.4] solution at doses of 154, 385, 770 and 1540 nmol Zn per mouse. Zn transfer was not significantly different between MT+/+ and MT-/- mice and was directly proportional to the oral dose (slope = 0.127, r = 0.991; 0.146, r = 0.994, respectively). Blood 65Zn and plasma Zn concentrations increased progressively in MT-/- mice at doses >154 nmol Zn, reaching levels of 2.4% of oral dose and 60/[micro]mol/L, respectively, at the 1540 nmol Zn dose. The corresponding values for MT+/+ mice were approximately half, 1.0% and 29/[micro]mol/L. Intergenotypic differences were found in tissue distribution of 65Zn within the body; MT-/- mice had higher 65Zn levels in muscle, skin, heart and brain, whereas MT+/+ mice retained progressively more Zn in the liver, in conjunction with a linear increase in hepatic MT up to the highest Zn dose. MT induction in the small intestine reached its maximum at an oral dose of 385 nmol Zn and did not differ at higher doses. Absorption of a 770 nmol 65Zn dose from a solid egg-white diet was only one fourth (MT+/+) and one eighth (MT-/-) of the Zn absorption from the same dose of 65Zn in aqueous solution. MT+/+ mice had greater (P < 0.05) Zn absorption from the egg-white diet than did MT-/- mice, indicating that gut MT confers an absorptive advantage, but only when Zn is incorporated into solid food. KEY WORDS: zinc, metallothionein, intestinal absorption, metallothionein-null mice

We conducted two trials (n = 144 and 96) to evaluate the response of feeding either ZnS[O.sub.4][multiplied by][H.sub.2]O or a zinc-lysine complex (ZnLys) in combination with various lysine levels on growth performance, liver, kidney, and 10th rib Zn concentration, serum Zn humoral immune response and absorption of Zn (chromic oxide method) of young pigs. The following treatments were started after a 7-d post-weaning adjustment during which all pigs were fed a common diet adequate in zinc. Diets were as follows: 1) basal 1 (B1), .8% dietary lysine without added Zn (basal contained 32 ppm Zn); 2) B1 plus 100 ppm Zn from ZnS[O.sub.4]; 3) B1 plus 100 ppm Zn from ZnLys, 4) basal 2 (B2), 1.1% lysine without added Zn; 5) B2 plus 100 ppm Zn from ZnS[O.sub.4]; 6) B2 plus 100 ppm Zn from ZnLys. In Trial 1 only, 100 ppm Zn from ZnS[O.sub.4] (diet 7) or ZnLys (diet 8) was added to a .95% lysine basal diet. The basal 20% CP diet contained 9.0% corn gluten meal to lower the total lysine level. Within lysine level, all diets were made isolysinic by using crystalline lysine. Zinc sulfate, ZnLys, or lysine replaced dextrose in the basal diet. After 4 wk on test, one barrow in each pen was killed; liver, kidney, left 10th rib, and contents of the stomach, small intestine, and lower colon were removed for Zn analyses. Performance (ADG and ADFI) was only improved (P < .05) in one of the two trials when either zinc source was added to the basal diets, but performance was higher (P < .01) for pigs fed 1.1% lysine diets compared with .8% lysine diets in both trials. Serum Zn concentrations were lower (P < .001) for pigs fed both dietary lysine basal diets without added Zn. The humoral response to sheep red blood cells and ovalbumin was not influenced (P > .20) by lysine level, or Zn level and source. Pigs fed diets without added Zn had lower (P < .001) liver, kidney, and rib Zn concentrations than pigs fed diets with added Zn regardless of Zn source. Dietary lysine did not influence liver Zn, but kidney (P < .01) and rib (P < .001) Zn concentrations were lower for pigs fed the higher lysine level. Digestibility coefficients of Zn were lower in the stomach for pigs fed diets without added Zn, similar among Zn levels and sources in the small intestine, and higher in the lower colon for pigs fed the basal diets without added Zn. Lysine level and Zn source did not influence Zn absorption. The ZnS[O.sub.4] and a zinc lysine complex seemed to be equally effective in promoting growth performance, zinc absorption, and tissue stores of young pigs when diets contained deficient, adequate, or slightly more than adequate levels of lysine. Key Words: Pigs, Zinc, Animal Tissues, Absorption

The mechanisms of stress-related hypozincemia were characterized in men and women based on the quantitative analysis of the time course of hypozincemia after the administration of lipopolysaccharide (LPS). Quantitative analysis of the time course of hypozincemia after LPS injection in human volunteers indicated the ability of low, safe doses of endotoxin to develop marked transient hypozincemia. Furthermore, hypozincemia was followed by reductions in serum albumin-zinc binding and increased urine zinc excretion.

The effect of marginal zinc restriction on bone zinc release was studied. Male weanling rats were fed zinc-adequate diet (12 mg zinc/kg diet) for 1 wk, intubated with 65Zn, refed the zinc-adequate diet for an additional week, and divided into one baseline group and five marginally zinc-restricted groups (6 mg/kg) and five corresponding zinc-adequate pair-fed groups. Significantly lower (P < 0.05) 65Zn radioactivity (10-20%) in the first week was observed in femurs of rats fed the marginally zinc-restricted diet without further change in the following weeks. Pair-fed rats showed higher 65Zn radioactivity in femurs in the second week, and the level was maintained. Similar results were found in tibia 65Zn radioactivity. Muscle zinc concentration was higher in the first week (P < 0.05) but subsequently returned to baseline levels in the second week through the fifth week. The results support the existence of two zinc pools in the skeleton, one a small, rapidly turning-over pool (10-20% in size), and the other a slowly turning-over pool. When rats suffer marginal zinc restriction, zinc from the readily turning-over bone pool is utilized for soft tissue needs, followed by decreased growth rate to maintain zinc homeostasis.

Acute intestinal inflammation was established in rats by intraluminal administration of acetic acid into loops of distal ileum, proximal jejunum or ascending colon. The study included two control groups of intact (untreated) rats and sham-operated (saline-treated) rats for each intestinal segment. A third group of rats received acetic acid. Histological evaluation demonstrated that acetic acid treatment induced a mild inflammatory response. Two days after treatment, zinc absorption was measured using ligated 10-cm loops of each segment in which 65Zn was injected intraluminally. 65Zn absorption by the ileum, jejunum and colon was markedly reduced in those rats in which inflammation was induced by acetic acid. The liver showed the highest uptake of radioisotope, but the relative tissue distribution generally followed the amount of absorption. The surgical procedure itself seemed to reduce zinc absorption. No changes in (3H)leucine absorption were observed between sham-operated and acetic acid-treated controls. There was no significant serosal arrow to the right luminal secretion of intramuscularly injected 65Zn in any of the studied segments. Therefore, based upon the data obtained, we conclude that acetic acid-induced intestinal inflammation reduces absorption of zinc by the small and large intestine, and that a surgical procedure (laparotomy) also reduces zinc absorption. The mechanism of this inflammation is such that malabsorption shows some specificity.

Two experiments were conducted to determine the effects of supplemental microbial phytase on utilization of dietary zinc by weanling pigs. Experiment 1 was a 2 X 3 factorial arrangement of treatments with 24 pigs for 4 wk. Two levels of phytase activity (0 and 1350 units/g) and three levels of zinc (0, 30 and 60 mg/kg as ZnSO4 center dot 7H2O) were added to a corn-soybean meal basal diet. Weekly measures included growth performance, plasma alkaline phosphatase activity and plasma mineral concentrations. In Experiment 2, mineral balances were determined in 12 pigs fed the basal diet or the diet with added zinc (30 mg/kg) or phytase (1350 units/g). The results indicated that either supplemental phytase or supplemental zinc increased plasma alkaline phosphatase activity and plasma zinc concentrations, but these increases were not additive. Supplemental phytase decreased plasma alkaline phosphatase activity in pigs supplemented with zinc. Supplemental phytase also significantly enhanced weight gain, feed intake, gain:feed ratio, plasma concentrations of inorganic phosphorus, and retention of phosphorus and calcium. Neither supplemental phytase nor zinc affected zinc retention. Supplementing corn-soybean meal diets with microbial phytase at 1350 units/g feed improves bioavailability of zinc as well as of phytate phosphorus to weanling pigs.

Zinc is a nontoxic metal that is indispensable in numerous functional proteins which take part in various physiologic processes. Its physicochemical properties makes it stable since it is amphoteric, free in solution and does not undergo reduction or oxidation. As an enzyme, either in metal-proteins and metal-metal complexes, ithas three functions: catalytic, coactive, anfd structural. It is also an integral component in two proteins: metallithioneins and gene regulatory proteins.

The pharmacokinetics of D(-)-penicillamine (PA) and its effects on zinc and copper levels in chicks were studied. Subcutaneous and intravenous injections of PA were eliminated from plasma with a fast and a slow component. In the liver and pancreas, elimination showed only the slow component. Oral administration evoked the bimodal pattern in plasma but the highest level was only 20% of that reached through injection. Urinary excretion of zinc and copper was found to be related to PA excretion and to increase in direct proportion to PA dose. PA can also modify zinc tissue distribution, and also that of copper, but to a lesser degree.

Zinc is an important cofactor of several enzymes that function in energy metabolism. Exercise has been found to induce changes in zinc homeostasis; thus, compromised zinc status may influence exercise [...]

Both thyroid hormone (triiodo-L-thyronine, [T.sub.3]) and zinc play important roles in growth and development. The [T.sub.3] receptor is thought to require zinc to adopt its biologically active conformation. Some of the effects of zinc deficiency, therefore, may be due to loss of zinc from the [T.sub.3] receptor and impairment of [T.sub.3] action. This possibility was investigated in growing rats by examining the effects of hypothyroidism and hyperthyroidism in zinc-deficient, pair-fed and control rats. Measurement of serum zinc and [T.sub.3] confirmed the efficacy of the treatments. Zinc deficiency and hypothyroidism resulted in lower food intake and growth failure, but no interaction was observed between the two treatments. Individual tissue weights were influenced by thyroid status as expected, regardless of zinc status. Both dietary and hormonal treatments influenced serum insulin-like growth factor (IGF)-I in an interactive manner. IGF-I was reduced to a greater extent in zinc-deficient than in pair-fed rats compared with controls. Both hypothyroidism and hyperthyroidism reduced serum IGF-I, and a greater reduction due to hyperthyroidism was apparent in zinc-deficient rats. IGF binding proteins were also influenced by diet and thyroid status. The hepatic expression of mRNA S14 was assessed as a direct index of the nuclear action of [T.sub.3], but its response was not influenced by dietary treatment. Although confirming the role of both [T.sub.3] and zinc in the regulation of growth and the somatotrophic axis, the growth failure of zinc deficiency does not appear to be due to impaired [T.sub.3] function. J. Nutr. 131: 1135-1141, 2001. KEY WORDS: * thyroid hormone * zinc * growth * rats

We investigated the effects of dietary zinc deficiency on skeletal metabolism in an animal model. Thirty 21-d-old male Sprague-Dawley rats were fed for 28 d either a zinc-deficient (ZD) diet (1 mg zinc/kg) or a normal diet ad libitum (AL, 50 mg zinc/kg) or in the same quantity as the ZD (pair-fed, PF). Only in the ZD group were general physical signs of zinc deficiency observed. Compared with the AL and PF rats, ZD rats showed significantly lower mean values in ponderal growth rate, femur weight and length, circulating levels of insulin-like growth factor-I, bone mechanical properties and concentration of zinc and, on histomorphometry, a decrease in the thicknesses of the overall growth plate and hypertrophic cartilage. In contrast, although bone volume was significantly lower in the ZD and PF rats than in the AL rats, no difference was observed between the ZD and PF rats. Osteoclast surface/bone surface and osteoclast number/bone surface ratios were significantly greater in PF rats than in the other two groups and not different in ZD and AL rats. Collectively, these data indicate that zinc deficiency has profound effects on the skeletal system of growing rats. In particular, the effects of zinc deficiency on bone growth and mass are the result of the reduced activity of the growth plate, likely mediated by impairment in the insulin-like growth factor-I system. We did not demonstrate an effect on bone mass via increased bone resorption. J. Nutr. 131: 1142-1146, 2001. KEY WORDS: * zinc deficiency * rats * histomorphometry * growth cartilage

There is substantial evidence to support an important role for zinc in immune processes. Adequate zinc status is essential for T-cell division, maturation and differentiation; lymphocyte response to mitogens; programmed cell death of lymphoid and myeloid origins; gene transcription; and biomembrane function. Lymphocytes are one of the types of cells activated by zinc. Zinc is the structural component of a wide variety of proteins, neuropeptides, hormone receptors and polynucleotides. Among the best known zinc-dependent hormones/ enzymes are Cu, Zn superoxide dismutase, an enzyme component of the antioxidant defense system, and thymulin, which is essential for the formation of T-lymphocytes. In animals and humans, zinc deficiency results in rapid and marked atrophy of the thymus, impaired cell-mediated cutaneous sensitivity and lymphopenia. Primary and secondary antibody responses are reduced in zinc deficiency, particularly for those antigens that require T-cell help, such as those in heterologous red blood cells. In addition, antibody response and the generation of splenic cytotoxic T cells after immunization are reduced. Zinc also inhibits the production of tumor necrosis factor, which is implicated in the pathophysiology of cachexia and wasting in acquired immune deficiency syndrome. J. Nutr. 130:1421S-1423S, 2000. KEY WORDS: * zinc * human immunodeficiency virus * nutrition * disease progression * supplementation

Although the intriguing role of zinc as an essential trace element for immune function is well established, particular progress in determining the molecular principles of action of this ion was made recently. Leukocyte responsiveness is delicately regulated by zinc concentration. Zinc deficiency as well as supraphysiologic levels impair immune function. Furthermore, the activities of many immunostimulants frequently used in immunologic studies are influenced by zinc concentration. Therefore, our knowledge from in vitro studies is widely dependent on the zinc concentration, and when not in physiologic range, immunologic responses are artificially low. Decreased production of TH1 cytokines and interferon-[Alpha] by leukocytes in the healthy elderly person is correlated with low zinc serum level. The defect in interferon-[Alpha] production is reconstituted by the addition of physiologic amounts of zinc in vitro. Interestingly, zinc induces cytokine production by isolated leukocytes. Zinc induces monocytes to produce interleukin-1, interleukin-6 and tumor necrosis factor-[Alpha] in peripheral blood mononuclear cells and separated monocytes. This effect is higher in serum-free medium. However, only in the presence of serum does zinc also induce T cells to produce lymphokines. This effect on T cells is mediated by cytokines produced by monocytes. Stimulation also requires cell-to-cell contact of monocytes and T cells. Information is presented to illustrate the concepts that the zinc concentration must be taken into account whenever in vitro studies are made or complex alterations of immune functions are observed in vivo. J. Nutr. 130:1407S-1411S, 2000. KEY WORDS: * trace elements * immunology * cell biology * human * review

The concentration of plasma zinc is the generally accepted index of zinc status. Although low plasma zinc is an essential criterion of deficiency, alone it is inadequate. To supplement this index, we sought to determine the first limiting biochemical defect in animals fed zinc-deficient diets and concluded that the limiting function is associated with a posttranslational change in plasma membrane proteins. Among the signs of zinc deficiency in rats is a bleeding tendency associated with failure of platelet aggregation, a phenomenon that correlates with impaired uptake of [Ca.sup.2+] when stimulated. Zinc-deficient guinea pigs exhibit signs of peripheral neuropathy, and their brain synaptic vesicles exhibit impaired [Ca.sup.2+] uptake when they are stimulated with glutamate. Red cells from zinc-deficient rats show increased osmotic fragility associated with decreased plasma membrane sulfhydryl concentration. Both phenomena are readily reversed (2 d) by dietary zinc repletion. Volume recovery is dependent on Ca-dependent K channels and the sulfhydryl redox state. Both the impaired aggregation and calcium uptake of zinc-deficient platelets are corrected by in vitro incubation of blood with glutathione. Considering the fact that plasma membranes from several cell types show impaired function that is associated with a decreased rate of calcium uptake, it is postulated that a defect in calcium channels is the first limiting biochemical defect in zinc deficiency. The calcium uptake defect and consequent impaired second-messenger function likely results from an abnormal sulfhydryl redox state in the membrane channel protein. J. Nutr. 130: 1432S-1436S, 2000. KEY WORDS: * zinc status * biochemical defect * sulfhydryl redox state * calcium channels * osmotic fragility * rats

Maintaining a constant state of cellular zinc nutrition, or homeostasis, is essential for normal function. In animals and humans, adjustments in zinc absorption and endogenous intestinal excretion are the primary means of maintaining zinc homeostasis. The adjustments in gastrointestinal zinc absorption and endogenous excretion are synergistic. Shifts in endogenous excretion appear to occur quickly with changes in intake just above or below optimal intake. The absorption of zinc responds more slowly, but it has the capacity to cope with large fluctuations in intake. With extremely low zinc intakes or with prolonged marginal intakes, secondary homeostatic adjustments may augment the gastrointestinal changes. These secondary adjustments include changes in urinary zinc excretion, a shift in plasma zinc turnover rates and, possibly, an avid retention of zinc released from selected tissues, such as bone, in other tissues to maintain function. J. Nutr. 130: 1360S-1366S, 2000. KEY WORDS: * zinc * zinc homeostasis * zinc absorption * zinc kinetics * zinc excretion

Metallothionein is a zinc-binding protein composed of more than 60 amino acid residues, a third of which are cyteines and eight are lysines. It was discovered in the 1950s but its crystal structure was elucidated in the early 1990s. Recent interest in metallothionein stems from its regulatory function in zinc metabolism. The different functions of zinc in the body are summarized.

Circular dichroism spectroscopy, sedimentation assays and immobilized metal ion affinity chromatography have been used in studying the effects of substituting Arg with histidine-13 (his-13) on the various Zn2+-induced aggreggation behavior in rat and human beta-amyloid peptides (A-beta). The latter are major components of amyloid deposition in Alzheimer's disease. Zinc ions have been observed to induce the rapid aggregation of (A-beta). Results indicate that the coordination of Zn2+ to his-13 is crucial in the Zn2+-induced aggregation of A-beta.