Zinc and Health: Workshop Summary
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.