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Session IV, Zinc and Cellular Mechanisms


Zinc and Health: Workshop Summary

Session IV

Session IV, Zinc and Cellular Mechanisms clearly brought the question forward on exactly how does the cell maintain zinc in an available form.  In order to be able to answer this question and others, such as, what is the free concentration of zinc in the cell, the development of new analytical methods and chemical probes will be essential. Additionally, much study is still needed to characterize the transporter proteins that are responsible for moving zinc about the cell and their associated receptors.  The use of chemical probes may provide insight into determining an individual's zinc status. One such index that might prove fruitful in gauging the zinc status of an individual is the measurement of the osmotic fragility of erythrocytes, as the red blood cell membrane provides an excellent model for the study of plasma membranes and their constituent calcium channel proteins.  It is postulated that a defect in calcium channels is the first limiting biochemical defect in zinc deficiency.  The use of in vitro preimplantation, peri-implantation, and post implantation embryo culture models have been employed to study the mechanisms underlying zinc-deficiency-induced teratogenesis. Cell cycle kinetics, cell differentiation, and gene expression are affected by zinc deficiency during development. Specifically, inappropriate apoptosis occurs in areas found malformed as a result of zinc deficiency. From these findings more questions have been generated such as what will be the effect of zinc supplements on fertility and small cellular systems undergoing rapid development. 

The importance of understanding a connection between the thermodynamics and kinetics of zinc enzyme catalytic sites, ligand coordination, and co-catalytic zinc sites consisting of multi-metal sites or valleys and side chain configurations were reviewed and highlighted. Our knowledge however, for the chemical role of zinc for transport proteins and chaperon proteins are much less clear.  Promising new work in the area of fluorescent probes may provide useful in monitoring zinc status from a nutritional point of view. 

When we think of zinc we must think globally and consider the importance of zinc  regulation in multicellular organisms, particularly in mammals, of complex zinc sites in control of hormonal responses, and the control of growth differentiation and regulation.  These events are well  characterized by the zinc finger proteins, not only in transcription, but in a variety of cellular responses.