THE METABOLISM OF CHENODEOXYCHOLIC ACID TO BETA-MURICHOLIC ACID IN RAT-LIVER
THE METABOLISM OF CHENODEOXYCHOLIC ACID TO BETA-MURICHOLIC ACID IN RAT-LIVER
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DOI：
10.1111/j.1432-1033.1983.tb07550.x
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
BOYD, GS
中科院分区：
文献类型：
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作者：
BOTHAM, KM;BOYD, GS
通过放射免疫测定法测量离体大鼠肝细胞中缀合鹅去氧胆酸和牛磺-β-鼠胆酸的合成。牛磺-β-鼠胆酸的产生在37°C下孵育4小时内呈线性。 C.共轭鹅去氧胆酸的净合成远低于牛磺-β-鼠胆酸的净合成。当从肠肝循环已被破坏的大鼠中制备肝细胞时，通过饲喂胆盐螯合剂考来烯胺或通过总胆汁引流48小时，牛磺-β-鼠胆酸的合成与来自对照大鼠的细胞相比增加。肝细胞孵育过程中结合鹅去氧胆酸的积累因消胆胺喂养而增加，但不因总胆汁引流而增加。在鹅去氧胆酸合成方面，两种破坏肠肝循环的方法之间可能存在代谢差异。饮食中给予 1% 胆固醇至少 2 周的大鼠制备的肝细胞合成的牛磺-β-鼠胆酸明显多于对照大鼠的肝细胞。然而，由胆固醇喂养动物的细胞合成的结合胆酸、鹅脱氧胆酸和牛磺-β-鼠胆酸的总量与来自正常大鼠的肝细胞产生的总量没有显着差异。外源牛磺鹅去氧胆酸被分离的肝细胞代谢为牛磺鼠胆酸。牛磺-β-鼠胆酸的产量在20μM牛磺鹅脱氧胆酸浓度下达到最大值。然而，牛磺鹅去氧胆酸的总代谢线性增加直至测量的最高浓度50μM。在总胆汁引流过程中，牛磺-β-鼠胆酸的胆汁含量在第一个10小时内迅速下降，此后继续下降，在大约10小时后达到最低值。 24小时。在剩余的实验期间没有观察到显着的上升。体外分离的肝细胞合成的结合鹅去氧胆酸大部分被代谢为牛磺-β-鼠胆酸，因此在使用该系统研究胆汁盐合成时有必要考虑到这一点。
The synthesis of conjugated chenodeoxycholic acid and tauro-.beta.-muricholic acid in isolated rat hepatocytes was measured by radioimmunoassay. Production of tauro-.beta.-muricholic acid was linear over 4 h of incubation at 37.degree. C. The net synthesis of conjugated chenodeoxycholic acid was very much lower than that of tauro-.beta.-muricholic acid. When hepatocytes were prepared from rats in which the enterohepatic circulation had been broken, either by feeding the bile salt sequestrant, cholestyramine or by total biliary drainage for 48 h, synthesis of tauro-.beta.-muricholic acid was increased compared to that in cells from control rats. Conjugated chenodeoxycholic acid accumulation during incubation of the hepatocytes was increased by cholestryamine feeding but not by total biliary drainage. There probably is a metabolic difference between the 2 methods of breaking the enterohepatic circulation with regard to chenodeoxycholic acid synthesis. Hepatocytes prepared from rats given 1% cholesterol in the diet for at least 2 wk synthesized significantly more tauro-.beta.-muricholic acid than those from control rats. The total amount of conjugated cholic, chenodeoxycholic and tauro-.beta.-muricholic acids synthesized by cells from cholesterol fed animals, however was not significantly different from that produced by hepatocytes from normal rats. Exogenous taurochenodeoxycholic acid was metabolized to tauromuricholic acid by isolated hepatocytes. Production of tauro-.beta.-muricholic acid reached a maximum at a concentration of 20 .mu.M taurochenodeoxycholic acid. The total metabolism of taurochenodeoxycholic acid, however, increased linearly up to the highest concentration measured, 50 .mu.M. The biliary content of tauro-.beta.-muricholic acid during total biliary drainage fell rapidly in the 1st 10 h and thereafter continued to decline, reaching a minimum after .apprx. 24 h. No significant rise was observed during the remainder of the experimental period. A large proportion of the conjugated chenodeoxycholic acid synthesized by isolated hepatocytes in vitro is metabolized to tauro-.beta.-muricholic acid, and therefore it is necessary to take this into account when using this system to study bile salt synthesis.