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 bilayer or micelle 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 systems will be studied with multiple-field nuclear magnetic resonance (NMR) techniques: 13C, 2H, and 1H spin relaxation times and (two-dimensional) nuclear Overhauser effects will be monitored and interpreted theoretically for both simple and mixed lipid micelles and vesicles. In digestive mixtures that mimic duodenal content after a fatty meal, aggregate structure and susceptibility to enzymatic hydrolysis will be investigated in parallel with a combination of 13C NMR, quasielastic light scattering (QLS), and kinetic methods. Finally, attention will be focused explicitly on protein conformation with a series of solution-state NMR studies of colipase-bile salt binding.
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