The objective of this proposal is to quantitatively evaluate the role of the gastrointestinal tract in human zinc (zn) homeostasis. The ability of the human to maintain Zn homeostasis over a very wide range of dietary Zn intake is well documented. Understanding is rudimentary, however, regarding the limits of adaptation and how adaptive mechanisms may be adversely affected by other dietary constituents, such as phytate, and disease states, especially those associated with malabsorption. This proposal combines multilumen intestinal perfusion/aspiration techniques with Zn stable isotope methodology and model based compartmental analysis to quantitate and localize absorption of exogenous Zn and secretion-reabsorption of endogenous Zn. The intestinal intubation/perfusion studies allow frequent sampling of intestinal contents during the post-prandial state from the stomach to the distal ileum. Administration of an intravenous Zn isotope prior to the studies will allow measurement of endogenously secreted Zn by isotope dilution. Compartmental analysis techniques will be used to analyze kinetic data over 9 days for 2 additional stable Zn isotopes given orally and intravenously at the time of the intestinal studies. Tracer and tracee data will be examined for plasma, red blood cells, urine and feces in conjunction with that of the postprandial intestinal sampling. The modelling techniques will be used to develop a short term post=prandial gastrointestinal model of Zn metabolism. The data will also be incorporated into a whole body compartmental model of Zn homeostasis. In these pilot studies, the effects on post-prandial Zn homeostasis of acute changes in dietary Zn intake will be examined in normal adults.
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