细胞色素P450与胆固醇稳态。

Cytochrome P450s and cholesterol homeostasis.

作者信息

Pikuleva Irina A

机构信息

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1031, USA.

出版信息

Pharmacol Ther. 2006 Dec;112(3):761-73. doi: 10.1016/j.pharmthera.2006.05.014. Epub 2006 Jul 26.

DOI:10.1016/j.pharmthera.2006.05.014

PMID:16872679

Abstract

By participating in pathways of cholesterol biosynthesis and elimination, different cytochrome P450 (P450 or CYP) enzymes play an important role in maintenance of cholesterol homeostasis. CYP51 is involved in cholesterol biosynthesis, whereas CYP 7A1, 27A1, 46A1, 7B1, 39A1, and 8B1 are the key enzymes in cholesterol catabolism to bile acids, the major route of cholesterol elimination in mammals. Cholesterol transformations to steroid hormones are also initiated by the P450 enzyme CYP11A1. Finally, one of the major drug-metabolizing P450s CYP3A4 seems to contribute to bile acid biosynthesis as well. The 9 P450s will be the focus of this review and assessed as drug targets for cholesterol lowering.

摘要

通过参与胆固醇生物合成和消除途径，不同的细胞色素P450（P450或CYP）酶在维持胆固醇稳态中发挥重要作用。CYP51参与胆固醇生物合成，而CYP 7A1、27A1、46A1、7B1、39A1和8B1是胆固醇分解为胆汁酸的关键酶，胆汁酸是哺乳动物胆固醇消除的主要途径。胆固醇向类固醇激素的转化也由P450酶CYP11A1启动。最后，主要的药物代谢P450之一CYP3A4似乎也有助于胆汁酸的生物合成。这9种P450将是本综述的重点，并作为降低胆固醇的药物靶点进行评估。