THE METABOLISM OF URSODEOXYCHOLIC ACID IN MAN

本研究的目的是探索代谢的 熊去氧胆酸和动物相关胆汁酸。 一个主要 目标将涉及转型的途径， 鹅去氧胆酸经双肠途径转化为熊去氧胆酸 细菌和肝酶。 的示威 熊去氧胆酸是海狸鼠（M. coypus）提供了研究肝途径的动物模型。 C. absonum将用于研究细菌， 从7-酮石胆酸制备熊去氧胆酸， 3 α-羟基-5 β-胆-6-烯-24-酸。 此外该 细菌7-脱羟基化特异性和途径 将检查鹅去氧胆酸和熊去氧胆酸 使用真杆菌属（Eubacterium spp.）V.P. I 12708. 的 3 α-羟基-5 β-胆-6-烯-24-酸和3 α- 羟基-5 β-胆-7-烯-24-酸作为中间体， 考虑到以及氨基酸缀合在 阻碍7-脱羟基化。 同时，我们将合成共轭物 熊去氧胆酸与牛磺酸和甘氨酸的类似物， 抗细菌解偶联，研究细菌解偶联的机理 以及这些类似物对胆固醇和 胆汁酸的合成。 最后，我们将研究 7 α-和7 β-羟基胆汁酸对胆汁分泌的调节作用 在大鼠体内的酸合成。

The goal of this investigation is to explore the metabolism of ursodeoxycholic acid and related bile acids in animals. A major objective will deal with the pathway for the transformation of chenodeoxycholic acid into ursodeoxycholic acid by both intestinal bacteria and hepatic enzymes. The demonstration that ursodeoxycholic acid is the major bile acid in the nutria (M. coypus) provides an animal model to study the hepatic pathway. Pure strains of C. absonum will be used to study the bacterial for- mation of ursodeoxycholic acid from 7-ketolithocholic acid and 3alpha-hydroxy-5beta-chol-6-en-24-oic acid. In addition, the specificity and pathway of bacterial 7-dehydroxylation of chenodeoxycholic acid and ursodeoxycholic acid will be examined with the use of pure strains of Eubacterium spp. V.P.I. 12708. The role of 3alpha-hydroxy-5beta-chol-6-en-24-oic acid and 3alpha- hydroxy-5beta-chol-7-en-24-oic acid as intermediates will be considered as well as the role of amino acid conjugation in hindering 7-dehydroxylation. Also, we will synthesize conjugates of ursodeoxycholic acid with analogs of taurine and glycine that resist bacterial deconjugation, study the mechanism of bacterial resistance and also the effect of these analogs on cholesterol and bile acid synthesis in the rat. Finally, we will study the effect of 7alpha-and 7beta-hyvdroxy bile acids on the regulation of bile acid synthesis in the rat.