Cholesterol, an essential molecule: Diverse roles involving cytochrome P450 enzymes

Kirsty J. McLean, Marcus Hans, Andrew W. Munro

Research output: Contribution to journalConference article

28 Citations (Scopus)

Abstract

Cholesterol is an essential molecule for eukaryotic life and is an important precursor for a wide range of physiological processes. Biosynthesis and homoeostasis of cholesterol are complex mechanisms that are tightly regulated and interlinked with activities of a number of cytochrome P450 enzymes. These P450s play central critical roles in cholesterol metabolism. Key roles include a rate-limiting reaction in the synthesis of cholesterol itself, and in the oxidative transformations of cholesterol into steroid hormones and bile acids. However, microbial P450s also have important roles that impinge directly on human cholesterol synthesis and oxidation. Recent data reveal that Mycobacterium tuberculosis (which infects more than one-third of the world's human population) uses P450s to initiate breakdown of host cholesterol as an energy source. Microbial P450s also catalyse industrially important transformations in the synthesis of cholesterol-lowering statin drugs, with clear benefits to humans. The present article reviews the various roles of P450s in human cholesterol metabolism, from endogenous P450s through to microbial oxidases that enable catabolism of human cholesterol, or facilitate production of statins that regulate cholesterol production with positive outcomes in cardiovascular disease.

Original languageEnglish
Pages (from-to)587-593
Number of pages7
JournalBiochemical Society Transactions
Volume40
Issue number3
Early online date22 May 2012
DOIs
Publication statusPublished - 1 Jun 2012
Externally publishedYes
EventBiochemical Society Annual Symposium: Frontiers in Biological Catalysis - Robinson College, Cambridge, United Kingdom
Duration: 10 Jan 201212 Jan 2012
https://www.rsc.org/events/detail/6826/annual-symposium-frontiers-in-biological-catalysis

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