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Deprotonation of zinc(II)-water and zinc(II)-alcohol and nucleophilicity of the resultant zinc(II) hydroxide and zinc(II) alkoxide in double-functionalized complexes: theoretical studies on models for hydrolytic zinc enzymes.

The factors governing the deprotonation ability of zinc(II)-water and zinc(II)-alcohol and nucleophilicity of the resultant zinc(II) hydroxide and zinc(II) alkoxide as complex models for zinc enzymes have been investigated through Hartree-Fock and density-functional theory methods with the 6-311++G(d,p) basis set. Our calculations showed that in these double-functionalized complexes (i.e., zinc complexes having both a zinc(II)-alcohol motif and a zinc(II)-water motif) zinc(II)-alcohol is preferred in deprotonation over zinc(II)-water (i.e., zinc(II)-alcohol has a much lower pK(a) than zinc-coordinated water in the same molecule). Natural bond orbital analysis revealed that zinc(II) alkoxides are more nucleophilic than their respective counterparts zinc(II) hydroxides. The analysis of the transition state in the transformation reaction from zinc(II) hydroxide species to zinc(II) alkoxide species indicates that zinc(II) alkoxides are the preferred deprotonated species not only thermodynamically but also kinetically. Further examination of the proposed mechanisms of the zinc(II) alkoxide-promoted transesterification path and the zinc(II) hydroxide-promoted hydrolysis path revealed the structures of the intermediates and energy diagrams in the reactions. These results, entitled double-functionalized complexes, for the first time, put a firm theoretical foundation of why the zinc(II)-alcoholic OH is a better model for hydrolytic zinc enzymes (having both stronger acidity and better nucleophilicity).

Alcohols↗

Over-expression of an Arabidopsis zinc transporter in hordeum vulgare increases short-term zinc uptake after zinc deprivation and seed zinc content.

Increasing the zinc content of cereal grains will be important for improving human nutrition. Improved plant zinc efficiency will lead to increased yields when available zinc is limiting plant growth. The aim of our work was to test how the over-expression of zinc transporters in cereals affects plant growth, seed mineral content, and zinc transport rates. Known zinc transporters from Arabidopsis were over-expressed in Hordeum vulgare cv. Golden Promise by means of a ubiquitin promoter. Multiple transgenic lines were obtained, and the locus number and expression levels were verified. Transgenic lines were tested in long-term growth and short-term uptake experiments. Seeds from transgenic lines grown in soil had higher zinc and iron contents than controls. Short-term uptake rates were higher in the transgenic lines after zinc deprivation. Resupply of zinc after a period of deprivation resulted in the rapid decrease in zinc uptake even in transgenic lines in which a zinc transporter gene was constitutively expressed. Similar to processes in yeast and Arabidopsis, we hypothesize that this rapid decrease in zinc transport activity may be caused by the degradation of transporters in response to zinc-sufficient conditions. In the long-term growth experiments, there were no significant differences between transgenic and control lines in leaf zinc content or shoot biomass under zinc-sufficient or -deficient conditions. However, root-to-shoot ratios were higher in the transgenic plants grown under low-zinc conditions; this could impact zinc acquisition under field conditions. Increased seed zinc and iron content by over-expression of a zinc transporter provides a new strategy for increasing the micronutrient content of cereals.

Arabidopsis Proteins↗

Zinc absorption, intraluminal zinc and intestinal metallothionein levels in zinc-deficient and zinc-replete rodents.

Zinc absorption, endogenous luminal zinc and intestinal metallothionein were examined in rats and mice fed zinc-deficient and zinc-replete diets for 5-7 days. Small intestinal luminal washings from undosed rodents fed the replete diet contained 18- to 20-fold more zinc than those from zinc-deficient animals. Isotope dilution by this endogenous zinc could account for apparent differences between the groups in absorption of 65Zn from oral doses of 0.1-0.2 mumol 65Zn. With larger (1-2 mumol) oral doses of 65Zn in mice, no difference between the dietary groups was found, although zinc-deficient rats still absorbed more zinc than zinc-replete controls. In mice, zinc absorption from perfused duodenum, jejunum and ileum also was not increased by zinc deficiency. With oral doses, food generally lowered zinc absorption where endogenous or exogenous zinc was present in the gastrointestinal tract; food in perfusates lowered uptake more than transfer. Polarographically determined metallothionein was highest in duodenum of mice. It was lowered by feeding the deficient diet for 5 days without an increase in zinc absorption. It was concluded that zinc absorption is homeostatically increased by zinc deficiency in rats but not in mice and that intestinal metallothionein levels do not affect zinc absorption in mice.

Administration, Oral↗

Iron and zinc nutriture of premenopausal women: associations of diet with serum ferritin and plasma zinc disappearance and of serum ferritin with plasma zinc and plasma zinc disappearance.

The Second National Health and Nutrition Examination Survey found low iron and zinc intakes and low serum ferritin in many premenopausal women. Therefore food frequency history, serum ferritin, plasma zinc, plasma zinc disappearance, and zinc turnover rate were measured in healthy premenopausal women. Plasma zinc disappearance and turnover rate were determined by inductively coupled plasma mass spectroscopic analysis of the plasma ratio of zinc 67 to zinc 68 before and 30 to 60 minutes after intravenous injection of 67Zn. Food frequency predicted serum ferritin concentration in 38 women and plasma zinc disappearance in 19. Frequent red meat intake was associated with higher serum ferritin concentration and a "normal" plasma zinc disappearance. Frequent milk intake was associated with lower serum ferritin concentration and a rapid plasma zinc disappearance. After exclusion of an outlier, in 18 women serum ferritin concentrations were lower when plasma zinc was < 70 micrograms/dl (p < 0.03), and plasma zinc disappearance and turnover rate were higher when serum ferritin was < 20 ng/ml (p < 0.05). Serum ferritin concentration and plasma zinc disappearance constant were inversely and nonlinearly related (R2 = 0.777, p = 0.0003). These findings suggest that avoidance of red meat increases the risk of iron and zinc deficiencies, and low serum ferritin concentrations suggest the possibility of low zinc nutriture.

Adult↗

The bioavailability and pharmacokinetics of three zinc salts: zinc pantothenate, zinc sulfate and zinc orotate.

In this study the authors compared the pharmacokinetics of three zinc salts after parenteral and oral administration to rabbits: zinc sulfate, a soluble mineral salt; zinc pantothenate, a soluble organic salt; and zinc orotate, an insoluble organic salt. The results obtained with the two soluble salts were not significantly different (p less than 0.05). Therefore they appear to be bioequivalent. The plasma concentration curve for zinc orotate shows a faster distribution (alpha) and elimination phase (beta) after parenteral administration, and a slower absorption phase (Ka) after oral administration, when compared with that of the other two salts. It was shown that the dissolution behaviour of these zinc salts in water does not correlate with the parameters found in vivo.

Administration, Oral↗

Homeostasis of zinc in marginal human zinc deficiency: role of absorption and endogenous excretion of zinc.

Although biochemical and immunologic aspects of mild or marginal human zinc deficiency have been well characterized, there is a paucity of data regarding the effects of prolonged marginal zinc deficiency on zinc homeostasis. It appears that human beings are able to maintain zinc homeostasis by increasing efficiency of zinc absorption and decreasing endogenous excretion of zinc when they are subjected to short-term dietary zinc restriction. However, a mild deficiency of zinc in human beings under usual circumstances is an outcome of chronic exposure to diets low in zinc lasting for many months and years. Therefore, it is important to determine whether or not the adapted zinc homeostasis during the short duration of dietary zinc deprivation is also maintained during a prolonged period of dietary zinc restriction. We assessed the efficiency of zinc absorption as well as endogenous zinc excretion during a 6-month period of dietary zinc restriction (63.1 mumol/day) in human volunteers by using a stable zinc (70Zn). Prolonged marginal zinc deficiency did not impair the functional role of endogenous zinc excretion in zinc homeostasis, but efficiency of zinc absorption was not sustained and decreased in the majority of our volunteers when the zinc-restricted diet was continued for 6 months. Such altered mechanisms of zinc homeostasis suggest that chronic human zinc deficiency warrants reassessment of dietary zinc requirement to preserve normal zinc status in the subsets of population that are vulnerable to zinc deficiency.

Adult↗

Tissue uptake of zinc in rats following the administration of zinc dipicolinate or zinc histidinate.

Tissue uptake of zinc was determined in rats fed a low zinc diet (less than 1 ppm Zn) and an adequate zinc diet (20 ppm Zn) following the intramuscular injection of either zinc dipicolinate (ZnPA2) or zinc histidinate (ZnHis). Significant differences were observed when dietary and treatment effects on zinc uptake were compared in pancreas, duodenum, jejunum, ileum, kidney, and liver. Zinc uptake by the pancreas was higher in rats fed adequate zinc than in rats fed low zinc regardless of which zinc complex was injected, suggesting that the pancreas has a role in zinc excretion. Since ZnHis was more readily taken up than ZnPA2 by the pancreas of rats on the zinc-adequate diet, zinc chelated by histidine may be more readily excreted than zinc chelated by picolinic acid. No differences in zinc uptake were observed in the intestinal segments from rats fed low zinc compared to rats fed adequate zinc. However, in rats fed low zinc, ZnPA2 was more readily taken up than ZnHis by all intestinal segments implying that zinc chelated by picolinic acid may be more available for storage or utilization by the small intestine than zinc chelated by histidine. Also, the ileum had the highest zinc uptake regardless of which zinc complex was injected. Since the ileum has the largest population of Paneth cells, and high zinc uptake observed in this segment of the small intestine suggests a role for Paneth cells in zinc homeostasis.

Animals↗

Zinc availability from zinc lipoate and zinc sulfate in growing rats.

The purpose of this study was to investigate the effect of zinc lipoate and zinc sulfate on zinc availability in growing rats. 6 . 6 male albino rats were fed purified diets based on corn starch, egg albumen, sucrose, soy bean oil and cellulose over a 4-week period (diet Ia: 10 mg Zn/kg as zinc sulfate, diet Ib: 10 mg Zn/kg as zinc lipoate, diet IIa: 10 mg Zn/kg as zinc sulfate +0.4% phytic acid, diet IIb: 10 mg Zn/kg as zinc lipoate +0.4% phytic acid, diet IIIa: 20 mg Zn/kg as zinc sulfate + 0.4% phytic acid, diet IIIb: 20 mg Zn/kg as zinc lipoate + 0.4% phytic acid). Zinc lipoate and zinc sulfate both proved to be highly available zinc sources. When 0.4% phytic acid were present in the diets, apparent zinc absorption was generally depressed but was higher from zinc lipoate in tendency than from zinc sulfate. Comparable results were evident for femur zinc, plasma zinc and metallothionein concentrations in liver tissues. This indicates that zinc lipoate could be a valuable zinc source under conditions of low zinc availability. Nevertheless the absence or presence of phytic acid was a more important factor influencing zinc availability than the type of zinc source investigated.

Alkaline Phosphatase↗

Effect of acute zinc depletion on zinc homeostasis and plasma zinc kinetics in men.

BACKGROUND: Zinc homeostasis and normal plasma zinc concentrations are maintained over a wide range of intakes. OBJECTIVE: The objective was to identify the homeostatic response to severe zinc depletion by using compartmental analysis. DESIGN: Stable zinc isotope tracers were administered intravenously to 5 men at baseline (12.2 mg dietary Zn/d) and after 5 wk of acute zinc depletion (0.23 mg/d). Compartmental modeling of zinc metabolism was performed by using tracer and mass data in plasma, urine, and feces collected over 6-14 d. RESULTS: The plasma zinc concentration fell 65% on average after 5 wk of zinc depletion. The model predicted that fractional zinc absorption increased from 26% to essentially 100%. The rate constants for zinc excretion in the urine and gastrointestinal tract decreased 96% and 74%, respectively. The rate constants describing the distribution kinetics of plasma zinc did not change significantly. When zinc depletion was simulated by using an average mass model of zinc metabolism at baseline, the only change that accounted for the observed fall in plasma zinc concentration was a 60% reduction in the rate constant for zinc release from the most slowly turning over zinc pool. The large changes in zinc intake, excretion, and absorption-even when considered together-only explained modest reductions in plasma zinc mass. CONCLUSION: The kinetic analysis with a compartmental model suggests that the profound decrease in plasma zinc concentrations after 5 wk of severe zinc depletion was mainly due to a decrease in the rate of zinc release from the most slowly turning over body zinc pool.

Adult↗

Studies to determine the usefulness of the zinc clearance test to diagnose marginal zinc deficiency and the effects of oral zinc supplementation for short children.

OBJECTIVE: To evaluate the usefulness of the body zinc clearance test in the diagnosis of marginal zinc deficiency and to estimate the efficacy of oral zinc supplementation on growth in short children. METHODS: Zinc status was evaluated in 30 (19 boys and 11 girls) Japanese children with short stature using the body zinc clearance test. Changes in growth after oral zinc supplementation (ZnSO4,7H2O; 5 mg/kg/day in two divided doses) were studied. RESULTS: Basal serum zinc concentrations were 75.0 +/- 12.7 micrograms/dl and zinc clearance values were 19.1 +/- 5.8 ml/kg/hour in the 30 subjects. The correlation coefficient between serum zinc concentrations and zinc clearance values was as small as -0.36. There were nine cases whose body zinc clearance values were high and serum zinc concentrations were low, indicating definite zinc deficiency. There were nine cases whose body zinc clearance values were high, despite normal serum zinc concentrations, indicating marginal zinc deficiency. The mean height velocity for males was 5.3 cm/year before zinc supplementation and 7.8 cm/year after the therapy; and the mean SD score for height for age improved from -1.85 to -1.53. The mean height velocity for females was 5.1 cm/year before zinc supplementation and 5.9 cm/year after the therapy, and the mean SD score for height for age changed from -2.02 to -2.03. CONCLUSION: The body zinc clearance test was much more useful than serum zinc concentrations in diagnosing marginal zinc deficiency. Oral zinc supplementation improved the height velocity in short males, but not in short females.

Administration, Oral↗

Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains.

We now recognize three distinct motifs of DNA-binding zinc proteins: (i) zinc fingers, (ii) zinc clusters, and (iii) zinc twists. Until very recently, x-ray crystallographic or NMR three-dimensional structure analyses of DNA-binding zinc proteins have not been available to serve as standards of reference for the zinc binding sites of these families of proteins. Those of the DNA-binding domains of the fungal transcription factor GAL4 and the rat glucocorticoid receptor are the first to have been determined. Both proteins contain two zinc binding sites, and in both, cysteine residues are the sole zinc ligands. In GAL4, two zinc atoms are bound to six cysteine residues which form a "zinc cluster" akin to that of metallothionein; the distance between the two zinc atoms of GAL4 is approximately 3.5 A. In the glucocorticoid receptor, each zinc atom is bound to four cysteine residues; the interatomic zinc-zinc distance is approximately 13 A, and in this instance, a "zinc twist" is represented by a helical DNA recognition site located between the two zinc atoms. Zinc clusters and zinc twists are here recognized as two distinctive motifs in DNA-binding proteins containing multiple zinc atoms. For native "zinc fingers," structural data do not exist as yet; consequently, the interatomic distances between zinc atoms are not known. As further structural data become available, the structural and functional significance of these different motifs in their binding to DNA and other proteins participating in the transmission of the genetic message will become apparent.

Amino Acid Sequence↗

Plasma and erythrocyte zinc concentrations and their relationship to dietary zinc intake and zinc supplementation during pregnancy in low-income African-American women.

OBJECTIVE: To evaluate the effects of usual dietary intake of zinc and of zinc supplementation during pregnancy on plasma and erythrocyte zinc concentrations. DESIGN: A randomized, double-blind, placebo-controlled trial. SUBJECTS: Low-income African-American women (n = 580) assigned randomly to groups at 19 weeks of gestation. INTERVENTION: A daily dose of zinc (25 mg) or a placebo until delivery. MAIN OUTCOME MEASURES: Plasma, erythrocyte, and dietary zinc levels. STATISTICAL ANALYSES: Multiple regression and repeated measures analysis of variance. RESULTS: In both the placebo and the supplemented groups, when all subjects were grouped by usual dietary zinc intake above or below the median (12 mg/day), results were the same: Women with high dietary zinc intake had higher erythrocyte zinc levels at the time of randomization and at all subsequent measurements during pregnancy than those who had low dietary zinc intake (P < or = .06; difference not significant for zinc-supplemented group); no difference was observed for plasma zinc levels. On the other hand, when the subjects were stratified at the median by total daily zinc intake (usual dietary zinc + 25 mg zinc supplement) during pregnancy, a significant difference in plasma zinc levels (P < .005) was found between women with high total zinc intake (mean = 38 mg/day) and low total intake (mean = 13 mg/day) at 26, 32, and 38 weeks of gestation; however, no such differences were found in erythrocyte zinc levels. APPLICATIONS: These results should help dietitians and other health professionals better understand the expected changes in plasma and erythrocyte zinc levels during pregnancy, and the relationship between dietary and supplemental zinc and zinc nutriture.

Adult↗

Changes in serum and prostatic zinc concentrations in rats after intraprostatic injection of zinc: Comparison of two forms of zinc delivery.

BACKGROUND: We investigated changes in zinc concentrations in serum and prostatic tissue after an intraprostatic injection of zinc, and compared two forms of zinc delivery: solution and liposome. METHODS: Ninety-six male Wistar rats were used in the study (24 controls, 72 test rats). The test animals were randomly divided into two groups and were injected intraprostatically with 2 mL of 0.04 mol/L zinc sulfate according to the form of zinc delivery. Nine rats in each test group were sacrificed 1 day, 7, 14 and 28 days after injection, and 24 normal rats were injected intraprostatically with 2 mL of distilled water as controls. Serum and prostatic zinc concentrations of each group were measured by inductively coupled plasma atomic emission spectrometry. Blood chemistries, routine urinalysis, urine culture and histopathologic examination were also performed. RESULTS: Serum zinc concentrations did not change significantly after the intraprostatic injection of zinc. Prostatic zinc concentrations were found to be significantly greater (P < 0.05) in zinc-injected groups than in the control group. The intraprostatic injection of zinc solution and zinc liposome increased zinc levels in both ventral and dorsolateral lobes significantly. Prostatic zinc levels increased progressively following injection, reaching a peak level in 7 days and maintaining a high value throughout the experimental period. The prostatic zinc level of the 1-day zinc liposome group was higher than that of the 1-day zinc solution group, while no significant difference was observed between the solution and liposome group in 7, 14, 28 days. No abnormal findings were observed in any of the laboratory and histopathologic examinations; however, an acute inflammatory response was observed in the 1-day groups. CONCLUSION: These findings suggest that an intraprostatic injection of zinc in normal rats increases and maintains the prostatic zinc level for at least 4 weeks without causing any systemic or local toxicities. These findings suggest the potentially important clinical applicability of local zinc to the treatment of chronic prostatitis.

Animals↗

Release of zinc from maternal tissues during zinc deficiency or simultaneous zinc and calcium deficiency in the pregnant rat.

Earlier studies have shown that diets that increase tissue catabolism reduce the teratogenic effects of zinc deficiency. The hypothesis that zinc may be released from body tissues when the metabolic state is altered was further tested. Nonpregnant Sprague-Dawley females were injected with 65Zn; after equilibration, the two major pools of zinc, bone and muscle had different specific activities, muscle being much higher. Females were mated and fed diets adequate in zinc and calcium, deficient in zinc alone or deficient in both zinc and calcium. Calculations using weight loss, zinc content of maternal bone and muscle and total zinc content of the fetus at term indicated that most of the zinc in the fetus at term in both the zinc-deficient and zinc-calcium-deficient groups came from breakdown of maternal muscle in the last 3 d of pregnancy. The relatively small amount of additional zinc released from bone in the zinc-calcium-deficient rats early in pregnancy was sufficient to prevent abnormal organogenesis. Specific activity of zinc in the zinc-deficient and zinc-calcium-deficient fetuses was equal and high, indicating that most zinc in these fetuses came from maternal tissues and from the same maternal sources in both groups. In contrast, specific activity of zinc in the fetuses from rats fed adequate zinc and calcium was less than 30% of that in either of the deficient groups; this is consistent with the hypothesis that most zinc accrued by these fetuses came directly from the diet.

Animals↗

Release and absorption of zinc from zinc oxide and zinc sulfate in open wounds.

The pharmacokinetic behaviours of zinc oxide and zinc sulfate when applied as single doses to full-thickness excised rat skin wounds were studied. In the zinc oxide group, the wound fluid zinc concentration increased slightly over the 48-h postoperative period due to increased solubilization of zinc oxide, attributed to increased protein concentration of the wound fluid. When zinc sulfate was applied to the wounds, the wound fluid zinc concentration decreased rapidly during the first 4 postoperative h and then at a slower rate. The changes in the serum zinc level followed essentially the same kinetic pattern as that of the wound fluid zinc levels. The zinc concentration of the wounded tissue remained almost constant in zinc oxide treated wounds whilst it diminished in zinc sulfate treated wounds. In conclusion, zinc oxide delivers zinc ions to wounds over an extended period of time which results in constant wound tissue zinc levels. In contrast, zinc sulfate rapidly delivers zinc ions which results in decreasing tissue zinc levels.

Adult↗

Bioavailability of zinc from zinc-histidine complexes. I. Comparison with zinc sulfate in healthy men.

Zinc supplementation is beneficial in some clinical conditions. Histidine has been shown to improve zinc absorption in animals. To test its influence on zinc absorption in humans, we studied the bioavailability of zinc from zinc-histidine complexes as compared to zinc sulfate in 10 healthy volunteers. Ingestion of zinc complexed with histidine at a ratio of 1:2 or 1:12 increased serum-zinc concentration 25% more than ingestion of zinc sulfate. Calculated uptake was 30-40% increased with zinc histidine over zinc sulfate. Urinary excretion was not different with any preparation. Application of 15 mg zinc as zinc histidine 1:2 gave an identical serum-zinc response as 45 mg zinc taken as zinc sulfate. Zinc histidine complexes are better absorbed than zinc sulfate in humans.

Adult↗

[Determination of metabolic availability of zinc and estimation of zinc requirements through changes in the activity of metallo-zinc enzymes].

Data on the zinc requirements of animals vary widely with the type of diet or kind of zinc compound considered, as they are dependent on the kind of definition and estimation of mineral requirements used which, in turn, are based on the analytical content of the mineral in the diet. Actually, requirements for a particular trace element are the same for any diet provided differences in the rate of absorption and metabolic availability of the element are taken into consideration. A suggestion is made in the present paper to utilize changes in the activity of different metallo-zinc enzymes as a method for determining the degree of metabolic availability of zinc. Within the framework of a repletion trial young male rats were fed a semisynthetic casein diet containing 1.2 ppm of zinc for a 14-day period of zinc depletion followed by a 15-day repletion period during which the rats received a diet containing 4.5 ppm or 12 ppm of zinc. In this trial the pattern of activity of the alkaline phosphatase in serum and in the femoral bones was studied and the level of pancreatic carboxypeptidase A and B was estimated. The data thus obtained were compared with those of pair-fed control animals and control animals fed a libitum. (96 ppm of dietary zinc). The results of the present trial show the metabolic availability of zinc can be determined by measuring the level of activity of these metallo-zinc enzymes. A suitable model was established. Moreover, attempts have been made to show in which way the zinc demands of growing, full-grown, pregnant and lactating animals may be estimated by measuring changes in the degree of activity of these metallo-zinc enzymes. A definition is, in this case, given by that amount of zinc which allows for an optimum activity of the different metallo-zinc enzymes. Such data are applicable only to a particular diet or are valid only for a particular zinc compound. Principally, it is much better to relate the Zn requirements of the animal to the level of absorbable and metabolically available zinc. The present model has been suggested to provide a possibility for measuring the metabolic availability of zinc in the body.

Alkaline Phosphatase↗

Metallothionein knockout and transgenic mice exhibit altered intestinal processing of zinc with uniform zinc-dependent zinc transporter-1 expression.

A role for metallothionein in intestinal zinc absorption has been the subject of considerable debate. If metallothionein affects zinc absorption, then those factors that induce metallothionein synthesis (e.g., heavy metals, hormones) should alter zinc absorption and homeostasis. The present studies used metallothionein transgenic mice (overexpressing) and metallothionein knockout mice (no expression of metallothionein-1 or metallothionein-2) to examine directly the effects of metallothionein on zinc absorption, independent of secondary effects that could be caused by metallothionein inducers. Zinc absorption was examined by administering a single oral zinc dose (0.5 mmol/kg) by feeding tube to metallothionein transgenic and metallothionein knockout mice and measuring the serum zinc concentration. Two hours after the dose, the serum zinc concentration was 2.3 times higher in metallothionein knockout mice than in their control strain. Conversely, the concentration was elevated only one third as much in the metallothionein transgenic mice as in their controls after the zinc dose. We found that the serum zinc concentration was inversely related to the level of metallothionein protein. The intestinal zinc content was higher in the metallothionein knockout mice, however, suggesting that metallothionein did not reduce zinc absorption by simply sequestering zinc in the mucosa. The expression of the zinc transporter ZnT-1 was directly related to the serum zinc level and was independent of the level of metallothionein. These results further support metallothionein as an important component for reducing the efficiency of zinc absorption at elevated zinc intakes.

Animals↗