Zinc metabolism and homeostasis: The application of tracer techniques to human zinc physiology

Tracer kinetic techniques based on zinc stable isotopes have a vital role i n advancing knowledge of human zinc physiology and homeostasis. These techn iques have demonstrated the complexity of zinc metabolism, and have been cr itical to estimating the size and interrelationships of those pools of zinc that exchange rapidly with zinc in plasma and which are likely to be espec ially important for zinc dependent biology. This paper presents findings fr om recent research linking a steady state compartmental model with non-stea dy state post-prandial sampling from the intestine, utilizing a combination of intestinal intubation/perfusion and stable isotope tracer kinetic techn iques. The gastrointestinal tract has a central role in maintaining whole b ody zinc homeostasis. While the fractional absorption of zinc from a meal d epends on the quantity of exogenous zinc and on such dietary factors as phy tic acid, the fractional absorption does not appear to be dependent on the size of the rapidly exchanging pool of the host. In contrast, the quantity of endogenous zinc excreted via the intestine is positively correlated with both the amount of absorbed zinc and the zinc `status' of the host, and th us this process has an equally critical role in maintaining zinc homeostasi s. The observed alterations in zinc metabolism in some disease states can b e understood in the context of known homeostatic processes. In other condit ions, however, such alterations as inflammation-associated hyperzincuria an d zinc redistribution, the links between homeostatic perturbation and cellu lar biology are yet to be explained. Thus the challenge remains for researc h at the whole body level to carefully characterize zinc distribution and e xchange under diverse circumstances, while research at the cellular level m ust elucidate the regulatory processes and the factors to which they respon d.