VITAMIN A TRANSPORT SYSTEMS

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The long-term goals of this project are to examine what factors affect the regulation of the vitamin A transport systems and the mechanism(s) by which such regulation is accomplished. Of particular interest for the proposed period are the specific binding proteins and specific enzymes that are necessary for the overall process of absorption of vitamin A. These include cellular retinol-binding protein, type two, (CRBP(II)), present in the small intestine and cellular retinol-binding protein (CRBP), present in the liver. The enzymes in the gut of interest are the carotene- cleavage enzyme, a microsomal retinal-reductase, and a microsomal lecithinretinol acyl transferase. A similar esterifying enzyme is present in liver. The work proposed will examine if these binding proteins and enzyme activities are coordinately regulated in both rat and human to ensure the efficient absorption of vitamin A. In rat, possible coordinate regulation will be examined 1) along the horizontal (duodenumjejunum-ileum) and vertical (crypt-villus) axes of the mature small intestine; 2) during development of the gut and liver; 3) during pregnancy and lactation; 4) during the adaptation of the small intestine that occurs after surgical resection or transposition; and 5) under the influence of varying intakes of vitamin A, as beta-carotene or retinyl ester. In liver, particular attention is given to a new ester synthase, lecithinretinol acyl transferase, which will be purified. Specific antiserum will be produced to examine, by RIA and immunohistochemistry, its possible cell-specific regulation in the parenchymal and stellate cells of the liver during development and with varying intake of vitamin A. Human CRBP(II) will be purified and used to define the vitamin A absorptive system in human. Particular attention will be given to the very premature infant to determine if the elements necessary for efficient absorption of vitamin A are being expressed.