Reaction: cholesterol + [reduced NADPHhemoprotein reductase] + O2 = (24S)-cholest-5-ene-3β,24-diol + [oxidized NADPHhemoprotein reductase] + H2O
For diagram of reaction click here.
Glossary: cholesterol = cholest-5-en-3β-ol
(24S)-24-hydroxycholesterol = (24S)-cholest-5-ene-3β,24-diol
Other name(s): cholesterol 24-monooxygenase; CYP46; CYP46A1; cholesterol 24S-hydroxylase; cytochrome P450 46A1
Systematic name: cholesterol,NADPHhemoprotein reductase:oxygen oxidoreductase (24-hydroxylating)
Comments: A P-450 heme-thiolate protein. The enzyme can also produce 25-hydroxycholesterol. In addition, it can further hydroxylate the product to 24,25-dihydroxycholesterol and 24,27-dihydroxycholesterol . This reaction is the first step in the enzymic degradation of cholesterol in the brain as hydroxycholesterol can pass the bloodbrain barrier whereas cholesterol cannot . The direct electron donor to the enzyme is EC 188.8.131.52, NADPHhemoprotein reductase .
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
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. 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]
3. 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]
4. 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]
5. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]