THE ROLE OF CONJUGATION REACTIONS IN ENHANCING BILIARY-SECRETION OF BILE-ACIDS
THE ROLE OF CONJUGATION REACTIONS IN ENHANCING BILIARY-SECRETION OF BILE-ACIDS
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DOI：
10.1042/bj2140923
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发表时间：
1983-01-01
影响因子：
4.1
通讯作者：
GOLLAN, JL
中科院分区：
文献类型：
--
作者：
VESSEY, DA;WHITNEY, J;GOLLAN, JL
通过1个亚甲基缩短胆酸的5-C羧酸侧链产生胆汁酸（去甲胆酸盐），其不是胆汁酸缀合酶的底物。在离体灌流的大鼠肝脏系统中，研究了去甲胆酸盐在完整肝脏中的代谢和胆汁分泌。当用14-20 μ M去甲胆酸盐溶液灌注大鼠肝脏10分钟时，在肝脏、静脉流出物和胆汁中发现了未结合形式的去甲胆酸盐。牛磺胆酸盐和甘氨胆酸盐均不能通过高压液相色谱法或快速原子轰击质谱法检测到。将去甲胆酸盐的肝摄取和胆汁分泌动力学与胆酸盐、牛磺胆酸盐和化学合成的牛磺胆酸盐进行了比较。后3种胆汁酸从灌注液中完全清除并有效分泌到胆汁中。然而，去甲胆酸盐从灌注液中提取不完全，这至少部分是由于其相对较低的肝脏摄取速率。此外，去甲胆酸盐分泌到胆汁中的速率相对于胆酸盐或化学合成的牛磺酸去甲胆酸盐的分泌大大降低，即使去甲胆酸盐在肝脏中的浓度相对较高。胆汁酸的结合极大地促进它们分泌到胆汁中。
Shortening the 5-C carboxylic acid side chain of cholic acid by 1 methylene group gave rise to a bile acid (norcholate) that was not a substrate for the bile acid-conjugating enzymes. The metabolism and biliary secretion of norcholate in intact liver was examined in the isolated perfused rat liver system. When rat livers were perfused with 14-20 .mu.M solutions of norcholate for 10 min, norcholate was found in the unconjugated form in liver, venous effluent and bile. Neither tauronorcholate nor glyconorcholate was detectable by high-pressure liquid chromatography or fast-atom-bombardment mass spectrometry. The kinetics of hepatic uptake and biliary secretion of norcholate was compared with that for cholate, taurocholate and chemically synthesized tauronorcholate. The latter 3 bile acids were completely cleared from the perfusate and efficiently secreted into the bile. However, norcholate was incompletely extracted from the perfusate, and this was shown to be at least partially due to its relatively lower rate of hepatic uptake. Furthermore, the rate of norcholate secretion into bile was greatly reduced relative to the secretion of cholate or chemically synthesized tauronorcholate, even though the concentration of norcholate in the liver was comparatively high. The conjugation of bile acids greatly facilitates their secretion into bile.