Gary W. Evans

Acrodermatitis enteropathica without hypozincemia: therapeutic effect of a pancreatic enzyme preparation due to a zinc-binding ligand.

The clinical course and intestinal absorption studies of a female infant who developed diarrhea after cessation of breast feeding, mood changes, and intermittently had mild perioral and perianal rashes are described. She showed a partial response to a pancreatic enzyme preparation which was attributed to its content of a zinc-binding ligand, picolinic acid. Complete recovery occurred on pharmacologic doses of zinc. Exacerbation occurred twice upon withdrawal of the oral zinc medication. The zinc concentrations of plasma and intestinal mucosa were normal.

Effect of Acute Infection and Endotoxemia on Zinc Absorption in the Rat

Summary Intestinal zinc absorption was found to be significantly increased during acute bacterial infection and endotoxemia in the rat. Although serum zinc concentrations were depressed, there was a significant accumulation of 65Zn in the livers of the stressed animals. This study demonstrates that acute inflammation produces a redistribution of zinc within the host, which results in both increased zinc absorption and retention. The authors thank Miss C. I. Grace, A. M. Hoagland, and J. Jones for their technical assistance.

Zinc transport by transferrin in rat portal blood plasma.

Abstract Zinc transport in mesenteric lymph and zinc distribution in portal plasma and venous plasma were examined in rats that had been given an oral dose of 65 Zn. Less than 1% of an oral dose of 65 Zn appeared in the mesenteric lymph over a period of 8 hr. In portal plasma, approximately 70% of the isotope recovered after gel-filtration chromatography was bound to a protein that was identified as transferrin on the basis of molecular weight and electrophoretic properties. In venous plasma, the major fraction of 65 Zn was bound to albumin while the remainder of the isotope was associated with higher molecular weight proteins including transferrin and α 2 -macroglobulins. These results demonstrate that zinc is transported from the intestine to the liver via the portal blood, and the results demonstrate that zinc is transported in portal plasma bound to transferrin.

Interaction of the glucose tolerance factor (GTF) with insulin

Abstract Partially purified glucose tolerance factor (GTF) which had been extracted from Brewers yeast was mixed with 125 I-insulin, and the solution was chromatographed on Sephadex G-50. Similarly, 125 I-insulin which had not been reacted with GTF was chromatographed. Insulin reacted with GTF produced a significantly greater effect on glucose uptake in epididymal tissue than that of native insulin. When GTF, exclusive of insulin, was chromatographed, the fraction which potentiated insulin activity had an elution volume greater than that of insulin. These results demonstrate that GTF binds to insulin. When insulin was reacted with acetic anhydride under conditions which acetylate the α and e amino groups, GTF binding to insulin was inhibited. These results suggest that the α and e amino groups of insulin may be involved in the binding of GTF to insulin.

Identification of a Low Molecular Weight 65Zn Complex in Rat Intestine

Summary A low-molecular-weight 65Zn complex was identified in the intestinal lumen and mucosa following oral administration of 65Zn to rats. Analysis of the 65Zn complex by thin layer chromatography indicates that the complex possesses properties markedly different from those of zinc salts and simple zinc-amino acid complexes. These experiments demonstrate that zinc is bound to a low-molecular-weight ligand as well as a variety of macromolecules in the intestine of the rat.

Homeostatic Regulation of Zinc Absorption in the Rat

Summary Zinc concentration of the intestine, zinc-65 uptake by the intestine and zinc-65 absorption were measured in control and zinc-deficient rats. As zinc deficiency progressed, zinc concentration of the intestinal mucosa decreased whereas both the amount of zinc-65 taken up by the mucosa and the absorption of the isotope increased. In addition, zinc concentration of the plasma was decreased in zinc-deficient animals. When zinc-deficient rats were injected with ZnCl2 prior to oral administration of zinc-65, the zinc concentration of both the plasma and the intestine increased and there was a concomitant decrease in both zinc-65 uptake by the intestine and absorption of the isotope. The results of these experiments suggest that zinc absorption is regulated, in part, by the zinc content of the intestinal mucosa which, in turn, is regulated by the zinc content of the plasma.

Transferrin function in zinc absorption and transport.

Summary Blood was drawn from the portal vein of rats immediately after the insertion of 65Zn into the duodenal lumen. Analysis of the plasma from the portal blood demonstrated that the major portion of absorbed 65Zn was bound to transferrin. When apotransferrin was incubated with 65Zn-la-beled basolateral plasma membranes, 60% of the isotope was removed from the membrane . Zinc-free albumin prepared with his-tidine removed 25% of the 65Zn from labeled membranes and histidine had no effect. These results demonstrate that transferrin functions in the absorption and transport of zinc.

Growth Stimulating Effect of Picolinic Acid Added to Rat Diets

Abstract Rats fed either a soybean protein-based diet or a casein-based diet supplemented with picolinic acid gained significantly more weight than rats fed unsupplemented diets. The zinc concentration of the kidneys from the rats fed the diets supplemented with picolinic acid was significantly greater than that of the rats fed the unsupplemented diets. Rats fed a pyridoxine-free diet formulated with vitamin-free casein and supplemented with picolinic acid gained significantly more weight than rats fed an unsupplemented pyridoxine-deficient diet. The zinc concentration of the kidneys from the rats fed the pyridoxine-deficient diet supplemented with picolinic acid was significantly greater than that of the rats fed the unsupplemented diet. Dietary zinc absorption and food efficiency were increased when rats were fed supplemental picolinic acid. The results suggest that picolinic acid may increase the bioavailability of dietary zinc and perhaps other divalent cations which results in increased food efficiency.

Isolation of a (copper, zinc)-thionein from the small intestine of neonatal rats.

Abstract A Cu- and Zn-binding protein was isolated from the small intestine of 5-day-old rats whose only source of these metals was maternal milk. Elution behavior on Sephadex G-75 indicated that the molecular weight of this protein was about 9,000 daltons. Furthermore, the protein exhibited low absorbance at 280 nm, was separated into two subfractions by DEAE Sephadex chromatography and had low aromatic amino acid and high cysteine content. The protein, therefore, meets the criteria for classification as a metallothionein. Evidence suggested that the metallothionein is located primarily in the distal portion of the small intestine.

Effect of Leukocytic Endogenous Mediator (LEM) on Zinc Absorption in the Rat

Summary Leukocytic endogenous mediator (LEM) was shown to produce a significant increase in the intestinal absorption of zinc within 7 hr after its administration to normal rats. Consistent with earlier studies, LEM also produced a significant decrease in the plasma zinc concentration and an increased hepatic uptake of this metal which further demonstrates that LEM may be a key intermediate in altering zinc homeostasis during inflammation.