Zhang J, Larsson O, Sjövall J
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Biochim Biophys Acta. 1995 Jun 6;1256(3):353-9. doi: 10.1016/0005-2760(95)00045-e.
The metabolism of 27-hydroxycholesterol and 25-hydroxycholesterol was studied in cultures of human diploid fibroblasts. Both steroids underwent 7 alpha-hydroxylation with subsequent oxidation to 7 alpha-hydroxy-3-oxo-delta 4 steroids. A minor fraction of the 27-hydroxysteroids was oxidized to acids. Competition experiments indicated that both hydroxycholesterols were hydroxylated by the same enzyme, different from cholesterol 7 alpha-hydroxylase. 7 alpha,25-Dihydroxycholesterol suppressed the activity of HMG-CoA reductase at least as effectively as 25-hydroxycholesterol whereas 7 alpha,25-dihydroxy-4-cholesten-3-one was a less effective suppressor. The results suggest that cholesterol might be converted to 7 alpha-hydroxylated bile acid precursors in extrahepatic tissues in vivo and that the regulation of the activity of HMG-CoA reductase by oxysterols might be modulated by 7 alpha-hydroxylation and subsequent oxidation by 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase.
在人二倍体成纤维细胞培养物中研究了27-羟基胆固醇和25-羟基胆固醇的代谢。两种类固醇都经历7α-羟基化，随后氧化为7α-羟基-3-氧代-δ4类固醇。一小部分27-羟基类固醇被氧化为酸。竞争实验表明，两种羟基胆固醇都由同一种酶进行羟基化，该酶不同于胆固醇7α-羟化酶。7α,25-二羟基胆固醇抑制HMG-CoA还原酶活性的效果至少与25-羟基胆固醇一样有效，而7α,25-二羟基-4-胆甾烯-3-酮是一种效果较差的抑制剂。结果表明，胆固醇在体内可能在肝外组织中转化为7α-羟基化胆汁酸前体，并且氧甾醇对HMG-CoA还原酶活性的调节可能受7α-羟基化以及随后由3β-羟基-δ5-C27-类固醇脱氢酶/异构酶氧化的调节。
