SPECTROSCOPIC STUDIES OF MODEL DIGESTIVE SYSTEMS

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Both the biliary secretion of membrane lipids and the intestinal digestion of acylglycerols are mediated by physiological detergents -- including bile salts, fatty acids, monoglycerides, and phospholipids. Each set of events relies on the formation of molecular aggregates, so that efficient transport and enzymatic hydrolysis may be accomplished. In order to develop a detailed molecular understanding of these processes, it is proposed to conduct a series of spectroscopic investigations that coordinate structural information on model digestive mixtures with their functions in the gastrointestinal tract. The dynamic structure of model biliary mixtures will be investigated with two-dimensional nuclear magnetic resonance (NMR) relaxation experiments: lipid-lipid arrangements, molecular mobility, and bilayer ordering will be assessed and correlated with enzymatic accessibilities. In lipid mixtures tat mimic three stages of glyceride digestion, quasielastic light scattering and 13C NMR measurements will be employed to delineate the size and surface features that make these substrates so susceptible to attack by the lipase-colipase system. Finally, attention will be focused explicitly on the conformation of colipase and its complexes with bile salt detergents, using a battery of 2D NMR techniques.