Zinc: Physiology and Health Effects

The biochemistry and physiology of Zn is summarized selectively giving attention to those aspects of this ubiquitous multitasked trace element that are most pertinent to human Zn homeostasis and the avoidance of the health effects of human Zn deficiency. Intracellular signaling, mammalian Zn transporters, and the interactions between them are of special importance in maintaining Zn homeostasis. Two Zn transporter families have major roles in Zn transport. The ZnT (solute-linked carrier (SLC30A)) proteins lower intracellular Zn by mediating Zn efflux from the cells or influx into intracellular vesicles. The ZIP family (SLC39a) promote Zn transport from the extracellular fluid or from intracellular vesicles into the cytoplasm. ZIP4 has a lead role in regulating Zn absorption, but its actions are linked to many of the ZIP and ZnT families of transporters as well as with metallothionein (MT) and with the metal-response element-binding transcription factor 1 (MTF1), an intracellular Zn sensor, characterized by erythematous skin lesions with onset in early to mid infancy. Other features of note are diarrhea and other GI features, psychological disturbance, alopecia, and, if not treated with Zn, a progressive downhill course and frequent infections. Zn deficiency has appropriately attracted special attention in young children trapped in impoverished communities with food insecurity and lack of diversity, including inadequate bioavailable Zn. Longitudinal growth failure and impaired immunity with frequent infections, especially diarrhea contributing to mortality, are among the effects of Zn deficiency. The most severe health effects of Zn deficiency occur in acrodermatitis enteropathica, an autosomal inherited defect of one of several polymorphisms of the SLC39A4 gene encoding the ZIP4 transporter. This disease is characterized by erythematous skin lesions with onset in early to mid infancy. Other frequent features are diarrhea, abdominal discomfort, nausea, alopecia, and psychological disturbance. If the severe Zn deficiency is not treated, there is characteristically a downhill course, with frequent infections attributable to multiple defects of the immune system, often with a fatal outcome in early childhood.