Search

Ecto 5' nucleotidase (5'NT) is an integral plasma membrane enzyme located on most mammalian cells, and it is zinc dependent. We assayed 5'NT activity in the lymphocytes of two groups of subjects. The first group of six subjects had a mild state of zinc deficiency, as measured on the basis of zinc levels in lymphocytes, granulocytes, and platelets, but were otherwise healthy. They received 50 mg zinc as acetate orally for 12 weeks. The second six subjects were normal human volunteers in whom a mild state of zinc deficiency was induced experimentally by dietary techniques (4.2 to 5.6 mg daily zinc intake). For the assay of 5'NT, intact lymphocytes were incubated with 8-14C-labeled inosine monophosphate as substrate. Product and substrate were separated by thin-layer chromatography. Zinc level in cells was measured by flameless atomic absorption technique. In the first group of subjects with zinc deficiency, the decreased activity of 5'NT was corrected and the cellular zinc levels were normalized by oral zinc supplementation (p less than 0.01). In the second group of subjects, the baseline data were compared with those in early zinc depletion (4 to 8 weeks) and late depletion periods (greater than 20 weeks). A decrease in the activity of 5'NT was observed during the early zinc depletion phase. Zinc levels in lymphocytes, granulocytes, and platelets decreased significantly only during the late zinc depletion phase (p less than 0.01). Plasma zinc level did not change even during the late zinc depletion phase. Our studies show that 5'NT activity may be a sensitive and useful indicator of mild deficiency of zinc in human subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell-mediated immunity in human subjects is affected adversely as a result of zinc deficiency. The mechanism by which a deficiency of zinc may affect lymphocyte proliferation and functions, is not well understood at present. Nucleoside phosphorylase (NPase), a purine catabolic pathway enzyme, is zinc dependent, and a congenital deficiency of this enzyme is known to affect adversely cell-mediated immunity. This effect has been related to an accumulation of toxic nucleotides in lymphocytes as a result of NPase deficiency. Inasmuch as the effect of zinc deficiency on the activity of NPase and the levels of nucleotides in human lymphocytes has not been previously reported, we assayed these parameters in human subjects with zinc deficiency before and after zinc supplementation. A mild deficiency of zinc was diagnosed in those having decreased zinc in two out of three cell lineages (less than 42 micrograms in granulocytes, less than 48 micrograms in lymphocytes, and less than 1.70 microgram in platelets, per 10(10) cells). In comparison with five subjects with sufficient zinc, six subjects with zinc deficiency showed a decrease in the activity of NPase (p = 0.01), an increase in adenosine diphosphate (ADP) level (p = 0.008), a decreased adenosine triphosphate (ATP)-to-ADP ratio (p = 0.0001), and an increase in both guanosine triphosphate (GTP) (p = 0.02) and deoxyadenosine triphosphate (dGTP) (p = 0.04 in the lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions.