I plan to develop a new, non-invasive technique to evaluate gastrointestinal lipolytic activity as a test of exocrine pancreatic function. The method involvs the synthesis of two types of esters of Rho-acid (PABA) in which the alcoholic moieties will be derived from glycerol and the acids will be palmitic acid and PABA; the esters will therefore be analgoues of triglycerides. In the first type, the amino group of PABA will be free and in the second type it will be acylated. Two of the compounds have been synthesized and their structures have been confirmed by n.m.r. and infrared spectroscopy. I will initially evaluate, In Vitro, the hydrolysis of these substrates by pancreatic lipase. I will then evaluate these compounds a indicators of pancreatic function in rats and dogs with spontaneous or experimentally induced pancreatic insufficiency. I will determine the optimal format for the test including the pre-test diet of the animals, the dose of the test substance, the timing of the sampling, nd the effects of the test of thedosage form of the test substance The lipid analogues will be administered orally or intraduodenally; PABA liberated from the compounds will be absorbed, conjugated in the liver and excreted in the urine. I will therefore determine, at intervals, the concentration of PABA in the blood and urine. The level of PABA in the blood or the extent of PABA excretion in theurine should provide an indirect index of exocrine pancreatic function. I will attempt to correlate the extent of PABA excreation with the degree of fat malabsorption. Should these studies be successful, they will form the basis for similar studies in humans with disorders such as cystic fibrosis or pancreatic insufficiency. The esters may also serve as the substrate for a sensitive assay of lipase activity.
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| Sloan, H R; Kerzner, B; Scobell, H D et al. (1985) Large scale production of glucose oligomers and polymers for physiological studies in humans. Prep Biochem 15:259-79 |
