Kurosawa T, Sato M, Watanabe T, Suga T, Tohma M
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
J Lipid Res. 1997 Dec;38(12):2589-602.
3Alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid (C27-5beta-cholestanoic acid) derivatives with different carbon-number side chains were incubated with rat liver 800 g supernatant to study the effect of the side-chain length on the beta-oxidation system in bile acid biosynthesis. The intermediate alpha, beta-unsaturated and beta-hydroxylated bile acids, and the corresponding degradation products, were quantitatively determined by gas chromatography. The longer side-chained derivatives (C28- and C29-5beta-cholestanoic acids) were converted into corresponding sidechain degradation products, and the alpha,beta-unsaturated and beta-hydroxylated intermediates were also produced. On the other hand, the shorter side-chained derivative (C26-5beta-cholestanoic acid) only gave alpha,beta-unsaturated intermediate. The total formation of intermediates and degradation products from corresponding substrates was in the order of C27- > C28- > C29- > C26-5beta-cholestanoic acids. In the case of clofibrate-treated rat liver 800 g supernatant, the formation of intermediates and final degradation products from C28- and C29-5beta-cholestanoic acids increased significantly. These longer side-chained analogues seemed to be subjected to beta-oxidation system(s) induced with clofibrate treatment. The effect of a terminal methyl group in the side chain of 5beta-cholestanoic acid on the oxidation system was also investigated using 3alpha, 7alpha, 12alpha-trihydroxy-27-nor-5beta-cholestanoic acid derivatives as enzymatic substrates. These derivatives gave corresponding side chain degradation products, but the formation of intermediates was not detected. The formation of side chain cleavage products from 27-nor-5beta-cholestanoic acid derivatives increased to 10 to 25-fold that of the controls by treatment with clofibrate. The results suggested that the beta-oxidation system for 27-nor-5beta-cholestanoic acid derivatives was different from that for C27-5beta-cholestanoic acid, despite their bile acid steroidal structure.
将具有不同碳原子数侧链的3α,7α,12α-三羟基-5β-胆甾烷-26-酸（C27 - 5β-胆甾烷酸）衍生物与大鼠肝脏800g上清液一起孵育，以研究侧链长度对胆汁酸生物合成中β-氧化系统的影响。通过气相色谱法定量测定中间产物α,β-不饱和及β-羟基化胆汁酸以及相应的降解产物。较长侧链衍生物（C28 - 和C29 - 5β-胆甾烷酸）转化为相应的侧链降解产物，同时也产生了α,β-不饱和及β-羟基化中间产物。另一方面，较短侧链衍生物（C26 - 5β-胆甾烷酸）仅产生α,β-不饱和中间产物。相应底物的中间产物和降解产物的总生成量顺序为C27 - > C28 - > C29 - > C26 - 5β-胆甾烷酸。在用氯贝丁酯处理的大鼠肝脏800g上清液的情况下，C28 - 和C29 - 5β-胆甾烷酸的中间产物和最终降解产物的生成量显著增加。这些较长侧链类似物似乎受到氯贝丁酯处理诱导的β-氧化系统的作用。还使用3α,7α,12α-三羟基-27-降-5β-胆甾烷酸衍生物作为酶促底物，研究了5β-胆甾烷酸侧链中末端甲基对氧化系统的影响。这些衍生物产生了相应的侧链降解产物，但未检测到中间产物的生成。用氯贝丁酯处理后，27-降-5β-胆甾烷酸衍生物的侧链裂解产物的生成量增加到对照的10至25倍。结果表明，尽管27-降-5β-胆甾烷酸衍生物与C27 - 5β-胆甾烷酸具有胆汁酸甾体结构，但它们的β-氧化系统不同。
