Harris R A, Rivera E R, Villemez C L, Quackenbush F W
Department of Biochemistry, Purdue University, Lafayette, Indiana.
Lipids. 1967 Mar;2(2):137-42. doi: 10.1007/BF02530913.
Cholesterol biosynthesis from acetate-2-(14)C by the livers of suckling rats, which is known to be relatively slow, was increased 2-3-fold within 24 hours after severing the bile duct. Cholesterol synthesis by sham-operated litter mates showed no change under similar treatment. Mevalonate biosynthesis from acetate-2-(14)C in vitro by recombined liver microsomal supernatant (105,000xg) fractions from suckling rats also was only 10% of that of comparable recombined fractions from normal controls (young adult rats which were consuming colony diet). Activity was not improved by combining either the microsomal or supernatant fraction from suckling rat livers with the complementary fraction from normal adult livers. On the other hand, activity was restored to 100% when microsomes from livers of duct-served suckling rats were combined with the supernatant fraction from normal controls. Likewise, recombined liver fractions prepared from adult rats fed synthetic diets exhibited low activity for mevalonate biosynthesis. Activity was restored by bile duct cannulation, but inhibited when cholic acid was infused into the cannulated animal. Therefore, surgical procedures which interrupt the enterohepatic recirculation of bile components lead to a restoration of cholesterol biosynthesis and, at least in the adult animal where cannulation studies are practicable, this effect can be reversed readily by bile acid infusion.A slow rate of fecal excretion of(14)C-cholic acid was observed in suckling rats and rats fed synthetic diets, apparently reflecting an efficient enterohepatic recirculation of bile salts. The data suggest that under these dietary conditions bile salt retention either directly or indirectly influences hepatic synthesis of cholesterol.
用乙酸-2-(14)C合成胆固醇的过程在乳鼠肝脏中进行得相对缓慢，已知在切断胆管后的24小时内，该过程会增加2至3倍。假手术的同窝仔鼠在类似处理下胆固醇合成没有变化。乳鼠肝脏重组肝微粒体上清液（105,000xg）组分在体外由乙酸-2-(14)C合成甲羟戊酸的量也仅为正常对照组（食用群体饲料的成年幼鼠）可比重组组分的10%。将乳鼠肝脏的微粒体或上清液组分与正常成年肝脏的互补组分合并，活性并未提高。另一方面，当胆管结扎的乳鼠肝脏微粒体与正常对照组的上清液组分合并时，活性恢复到100%。同样，用合成饲料喂养的成年大鼠制备的重组肝组分对甲羟戊酸生物合成的活性较低。胆管插管可恢复活性，但向插管动物注入胆酸时活性受到抑制。因此，中断胆汁成分肠肝循环的外科手术会导致胆固醇生物合成恢复，并且至少在可行插管研究的成年动物中，这种作用可通过注入胆汁酸轻易逆转。在乳鼠和喂食合成饲料的大鼠中观察到(14)C-胆酸的粪便排泄率较低，这显然反映了胆汁盐有效的肠肝循环。数据表明，在这些饮食条件下，胆汁盐的保留直接或间接影响肝脏胆固醇的合成。
