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大鼠肝脏分离的非实质细胞和肝细胞对5β-胆甾烷-3α,7α,12α-三醇的26-羟化作用

26-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol by isolated nonparenchymal cells and hepatocytes from rat liver.

作者信息

Dueland S, Pedersen J I, Drevon C A, Björkhem I

出版信息

J Lipid Res. 1982 Dec;23(9):1321-7.

PMID:7161561
Abstract

The ability of isolated nonparenchymal and parenchymal rat liver cells to metabolize 5beta-cholestane-3alpha,7alpha,12alpha-triol and other bile acid intermediates has been investigated. Incubation of nonparenchymal cells with 5beta-cholestane-3alpha,7alpha,12alpha-triol resulted in the formation of one more polar product identified as 5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol. The formation was linear with time up to 2 hr and with the number of cells, and showed saturation kinetics with respect to substrate concentration. The maximum rate of conversion was 90 pmol/10(6) cells per hr. Incubation of hepatocytes with the triol resulted in the formation of several more polar products. In addition to 5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol, products with retention time on high pressure liquid chromatography identical with 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acid and cholic acid were observed. The identity of these products was verified by combined gas-liquid chromatography-mass spectrometry. The rate of conversion was linear with time for about 10 min and saturation with respect to substrate concentration was not attained. At identical substrate concentrations, the total rate of conversion (12.5 nmol/10(6) cells per hr) was at least two orders of magnitude higher than with the nonparenchymal cells. Similar differences in rates of conversion were observed with other C(27)-bile acid intermediates. It is concluded that the nonparenchymal cells do not play any significant role in the conversion of bile acid intermediates, either under physiological conditions or under experimental conditions where such steroids have been administered intravenously.-Dueland, S., J. I. Pedersen, C. A. Drevon, and I. Björkhem. 26-Hydroxylation of 5beta-cholestane-3alpha,7alpha,12alpha-triol by isolated nonparenchymal cells and hepatocytes from rat liver.

摘要

已对分离出的大鼠非实质肝细胞和实质肝细胞代谢5β-胆甾烷-3α,7α,12α-三醇及其他胆汁酸中间体的能力进行了研究。用5β-胆甾烷-3α,7α,12α-三醇孵育非实质细胞,导致形成了一种极性更强的产物,鉴定为5β-胆甾烷-3α,7α,12α,26-四醇。该形成过程在长达2小时内与时间呈线性关系,与细胞数量也呈线性关系,并且相对于底物浓度呈现饱和动力学。最大转化率为每小时90皮摩尔/10⁶个细胞。用三醇孵育肝细胞导致形成了几种极性更强的产物。除了5β-胆甾烷-3α,7α,12α,26-四醇外,还观察到在高压液相色谱上保留时间与3α,7α,12α-三羟基-5β-胆甾烷-26-酸和胆酸相同的产物。这些产物的同一性通过气液色谱-质谱联用得以验证。转化率在约10分钟内与时间呈线性关系,且未达到相对于底物浓度的饱和状态。在相同底物浓度下,总转化率(每小时12.5纳摩尔/10⁶个细胞)比非实质细胞至少高两个数量级。用其他C₂₇胆汁酸中间体也观察到了类似的转化率差异。得出的结论是,无论是在生理条件下还是在静脉注射此类类固醇的实验条件下,非实质细胞在胆汁酸中间体的转化过程中都不发挥任何重要作用。 - 杜兰德,S.,J. I. 佩德森,C. A. 德雷冯,和I. 比约克姆。大鼠肝脏分离的非实质细胞和肝细胞对5β-胆甾烷-3α,7α,12α-三醇的26-羟基化作用。

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26-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol by isolated nonparenchymal cells and hepatocytes from rat liver.大鼠肝脏分离的非实质细胞和肝细胞对5β-胆甾烷-3α,7α,12α-三醇的26-羟化作用
J Lipid Res. 1982 Dec;23(9):1321-7.
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Lipids. 1999 Apr;34(4):395-405. doi: 10.1007/s11745-999-0378-4.

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