EC 1.14.14.25 - Cholesterol 24-hydroxylase

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IntEnz Enzyme Nomenclature
EC 1.14.14.25

Names

Accepted name:
cholesterol 24-hydroxylase
Other names:
cholesterol 24-monooxygenase
CYP46
CYP46A1
cholesterol 24S-hydroxylase
cytochrome P450 46A1
Systematic name:
cholesterol,NADPH—hemoprotein reductase:oxygen oxidoreductase (24-hydroxylating)

Reaction

Cofactor

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 [2]. This reaction is the first step in the enzymic degradation of cholesterol in the brain as hydroxycholesterol can pass the blood—brain barrier whereas cholesterol cannot [3]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase [3].

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , DIAGRAM , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Protein domains and families: PROSITE:PDOC00081
Structural data: CSA , EC2PDB
Gene Ontology: GO:0033781
UniProtKB/Swiss-Prot:

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: 7238-7243 (1999). [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: 45-48 (2001). [PMID: 11698143]
  3. Mast, N., Norcross, R., Andersson, U., Shou, M., Nakayama, K., Björkhem, I. and Pikuleva, I.A.
    Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain.
    Biochemistry 42: 14284-14292 (2003). [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: 22980-22988 (2003). [PMID: 12686551]
  5. Russell, D.W.
    The enzymes, regulation, and genetics of bile acid synthesis.
    Annu. Rev. Biochem. 72: 137-174 (2003). [PMID: 12543708]

[EC 1.14.14.25 created 2005 as EC 1.14.13.98, transferred 2016 to EC 1.14.14.25]