IUBMB Enzyme Nomenclature

EC 1.14.13.98

Accepted name: cholesterol 24-hydroxylase

Reaction: cholesterol + NADPH + H+ + O2 = (24S)-24-hydroxycholesterol + NADP+ + H2O

For diagram click here.

Glossary: cholesterol = cholest-5-en-3β-ol

Other name(s): cholesterol 24-monooxygenase; CYP46; CYP46A1; cholesterol 24S-hydroxylase; cytochrome P450 46A1

Systematic name: cholesterol,NADPH:oxygen oxidoreductase (24-hydroxylating)

Comments: A heme-thiolate protein (P-450). The enzyme can also produce 25-hydroxycholesterol. In addition, it can further hydroxylate the product to 24,25-dihydroxycholesterol and 24,27-dihydroxycholesterol [2]. This reaction is the first step in the enzymatic degradation of cholesterol in the brain as hydroxycholesterol can pass the blood—brain barrier whereas cholesterol cannot [3].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 50812-30-1, 213327-78-7

References:

1. Lund, E.G., Guileyardo, J.M. and Russell, D.W. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc. Natl. Acad. Sci. USA 96 (1999) 7238-7243. [PMID: 10377398]

2. Mast, N., Norcross, R., Andersson, U., Shou, M., Nakayama, K., Bjorkhem, I. and Pikuleva, I.A. Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry 42 (2003) 14284-14292. [PMID: 14640697]

3. Lund, E.G., Xie, C., Kotti, T., Turley, S.D., Dietschy, J.M. and Russell, D.W. Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. J. Biol. Chem. 278 (2003) 22980-22988. [PMID: 12686551]

4. Bogdanovic, N., Bretillon, L., Lund, E.G., Diczfalusy, U., Lannfelt, L., Winblad, B., Russell, D.W. and Björkhem, I. On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci. Lett. 314 (2001) 45-48. [PMID: 11698143]

5. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]

[EC 1.14.13.98 created 2005]


Return to EC 1.14.13 home page
Return to EC 1.14 home page
Return to EC 1 home page
Return to Enzymes home page
Return to IUBMB Biochemical Nomenclature home page