The oligosaccharidases lactase and sucrase-dextrinase undergo dramatic alterations during development of the mammalian small intestine. In order to investigate the mechanisms relating to these dynamic events, the synthesis and membrane-associated assembly of these two enzymes will be studied in the maturing rat. Antibodies monospecific for lactase and sucrase-dextrinase will be used in combination with advanced techniques for intestinal perfusion and isolation of cellular organelles well established in the sponsor's laboratory to investigate molecular level events in the in vivo synthesis and assembly of these enzymes in the normally developing intestine. With these studies as a basis, regulation of the developmental alterations of lactase and sucrase-dextrinase by specific intraluminal carbohydrate substrates will be investigated at the molecular level using the above techniques in combination with a unique experimental model developed by the candidate. This model, in which nutrients adequate for normal growth are intravenously administered to infant animals prior to and during the weaning period, makes possible investigation of specific intraluminally administered nutrients without introduction of artifact due to malnutrition. These studies should generate precise information on regulation of synthesis and assembly of lactase and sucrase-dextrinase in the developing intestine and the mechanisms by which these enzymes are modulated by luminal nutrients during intestinal maturation.
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