The bile acids play an essential role in bile water formation, the solubilization of bile constituents, and the dispersion of the products of lipolysis. The bile acids are hydroxylated, acidic steroidal substances, usually containing 24 carbon atoms per molecule. During the past decade the Principal Investigator has examined questions that relate to the development of bile acid synthesis, secretion and absorption in the newborn and fetus. In the course of the most recent of these studies, it has been shown that a new class of bile acids, with shortened side-chains, exist in the meconium of normal newborn infants. Specifically, it has been established that a C20 bile acid, 3Alpha-hydroxy-5Alpha-etianic acid, is present in meconium in quantities comparable to those of standard C24 bile acids, and that other C20-22 bile acids are also present. In the proposed studies C20-22 bile acids and certain other a typical bile acids will be studied in meconium. Their structures will be characterized definitively through the synthesis of standards, and through gas chromatogrphy-mass spectroscopy. After identification, these substances will be sought in samples of meconium from newborn infants of varied gestational age and development. Other biological materials from infants and adults, and from laboratory animals will be examined for their presence. The metabolism of these aberrant bile acids will be studied. Since certain of them are potential cholestatic agents, their effect on bile flow will be examined, and yheir occurrence in cholestatic disease of the newborn will be determined.
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