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Supplement

Kinetics of Zinc Metabolism: Variation with Diet, Genetics and Disease^{1 ,2}

Meryl E. Wastney^*3, William A. House, Ramon M. Barnes^** and Kolinjavadi N. Siva Subramanian^*

^* Division of Neonatology, Department of Pediatrics, Georgetown University Medical Center Washington, D.C. 20007, Plant, Soil and Nutrition Laboratory, U.S. Department of Agriculture ARS, Ithaca, NY 14853-2901 and ^** Department of Chemistry, University of Massachusetts, Amherst, MA 01003-4510

³To whom correspondence should be addressed.

Kinetic studies are used to investigate metabolic processes. By adding an isotope to a system and measuring its movement in the system over time, pool sizes and transport rates can be determined by mathematically modeling the data. This approach enables rate differences to be determined in conditions that have been modified by diet, environment, genetics or disease. Kinetic studies in humans have shown that there are multiple pools of zinc that turnover from minutes to years and that processes, including zinc absorption and excretion, are regulated to maintain tissue levels when zinc intake varies. Animal studies allow for greater understanding of kinetics because more tissues can be sampled and environmental and genetic factors can be controlled. Kinetic studies in animals will provide information on the overexpression or the deletion of genes coding for specific proteins involved in zinc transport and metabolism. The advances that have been made in our understanding of the role of zinc in metabolism have been aided by the development of techniques for measuring isotopes in biological materials. In the future, the kinetics of zinc bound to different compounds will be measured. Modeling will enable this information, at the molecular level, to be integrated with knowledge of zinc metabolism at the cellular, organ and whole body level. To understand more fully the role of zinc in human health, kinetic studies are needed in healthy and disease states to identify differences in metabolic processes. This knowledge can be used as a basis for dietary and therapeutic recommendations.

KEY WORDS: • humans • rats • zinc mathematical modeling • compartmental model

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