Miki S, Cohen B I, Mikami T, Mosbach E H
Department of Surgery, Beth Israel Medical Center, New York, NY 10003.
J Lipid Res. 1993 Jun;34(6):915-21.
The hepatic metabolism and the choleretic effect of homochenodeoxycholic acid, the C25 homologue of chenodeoxycholic acid, were investigated in the hamster. After intravenous administration of 3H-labeled homochenodeoxycholic acid into biliary fistula hamsters, more than 80% of the radioactivity was recovered in bile in 4 h. A relatively small proportion of homochenodeoxycholic acid was present in bile as the taurine (22%) or glycine (4%) conjugate. However, more than 70% of the administered compound was biotransformed into C23 bile acids. The major C23 metabolites in bile were norchenodeoxycholic acid (17%), tauronorchenodeoxycholic acid (33%), and a trihydroxy norbile acid (identified as 3 alpha, 5 beta, 7 alpha-trihydroxy-24-nor-5 beta-cholan-23-oic acid, 19%). Small amounts (< 5%) of sulfate(s) and glucuronide(s) were also detected. Homochenodeoxycholic acid, when infused intravenously into the hamster, produced a striking choleresis. The increase in bile flow after infusion of this compound was 6- to 7-times that induced by chenodeoxycholic acid. The apparent choleretic activity of homochenodeoxycholic acid, 181 microliters/mumol, was much greater than that of chenodeoxycholic acid, 11 microliters/mumol. In conclusion, homochenodeoxycholic acid induced a hypercholeresis of the same order of magnitude as norchenodeoxycholic acid, presumably because considerable proportions of this compound were degraded to the hypercholeretic norchenodeoxycholic acid via beta-oxidation in the liver.
在仓鼠身上研究了鹅去氧胆酸的C25同系物高鹅去氧胆酸的肝脏代谢及利胆作用。给胆管瘘仓鼠静脉注射3H标记的高鹅去氧胆酸后，4小时内超过80%的放射性在胆汁中回收。高鹅去氧胆酸以牛磺酸（22%）或甘氨酸（4%）结合物形式存在于胆汁中的比例相对较小。然而，超过70%的给药化合物被生物转化为C23胆汁酸。胆汁中的主要C23代谢产物是去氧鹅去氧胆酸（17%）、牛磺去氧鹅去氧胆酸（33%）和一种三羟基去甲胆汁酸（鉴定为3α,5β,7α-三羟基-24-去甲-5β-胆烷-23-酸，19%）。还检测到少量（<5%）的硫酸盐和葡萄糖醛酸结合物。当给仓鼠静脉输注高鹅去氧胆酸时，会产生显著的利胆作用。输注该化合物后胆汁流量的增加是鹅去氧胆酸诱导的6至7倍。高鹅去氧胆酸的表观利胆活性为181微升/微摩尔，远大于鹅去氧胆酸的11微升/微摩尔。总之，高鹅去氧胆酸诱导的胆汁分泌过多与去氧鹅去氧胆酸处于同一数量级，推测是因为该化合物相当一部分通过肝脏中的β-氧化降解为具有利胆作用的去氧鹅去氧胆酸。
