Role of zinc in plasma membrane function.
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(2+) when stimulated. Zinc-deficient guinea pigs exhibit signs of peripheral neuropathy, and their brain synaptic vesicles exhibit impaired Ca(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.
O'Dell
B L
BL
Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D003677:Deficiency Diseases / Q000188:drug therapy / Q000503:physiopathology; D004032:Diet; D008565:Membrane Proteins / Q000378:metabolism*; D009752:Nutritional Status; D009996:Osmotic Fragility; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000378:metabolism; D015032:Zinc / Q000097:blood / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*
D015220:Calcium Channels; D008565:Membrane Proteins; D013438:Sulfhydryl Compounds; D015032:Zinc