Biotin is an important vitamin that is required for normal cellular function, growth and development. Mammals cannot synthesize biotin, therefore, they must obtain all their requirements of the vitamin by absorption in the gut. Limited nutritional studies are available describing the biotin absorption process, its regulation and the factors that affect the process leading to impairment in normal biotin status. Also, changes in the biotin absorption process in response to dietary manipulations and body requirements under certain conditions are not known. This gap in our understanding of biotin nutrition has also contributed to the uncertainly regarding the dietary requirements of biotin since the extent of absorption of biotin synthesized by intestinal flora in the distal part of the gut is not clear. Recent studies from our laboratory have characterized certain features of the biotin absorption process. In this proposal we plan to extend these studies to provide comprehensive information regarding the details of the absorption process of the vitamin. We will characterize the individual events of the biotin absorption process, i.e., movement of biotin across the brush border membrane and the basolateral membrane of the enterocyte and determine the factors that affect and regulate these processes. The effect of pharmacological agents (carbamazepin, phenytoin, primidon and phenobarbital, which have shown to impair biotin status in humans) on the events of biotin absorption will be examined. Since biotin is essential for normal growth and development (process which are especially active in the infancy period), biotin deficiencies occur in certain conditions in infancy and that intestinal functional are known to undergo maturational changes during early stages of life, studies on biotin absorption during development (suckling and weanling periods) are important and will be examined in this study. Aging is associated with a decrease in the plasma biotin level. Since changes in intestinal absorption of certain nutrients occur with aging, we will study biotin absorption process in aged animals to determine possible involvement of the intestine in causing this change in biotin levels. Finally, we will examine the regulation of biotin absorption by dietary manipulations, i.e., by increasing or decreasing biotin levels in the diet. The rat be used as an animal model in all our studies. The results of these study will provide important nutritional information, which is currently lacking, regarding biotin absorption and about the factors that affect and regulate the process. This information will also help us understand how certain drugs affect biotin status and will clarify some of the uncertainties regarding the dietary requirements of biotin.
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