Reaction: cholesterol + reduced acceptor + O2 = 25-hydroxycholesterol + acceptor + H2O
For diagram of reaction click here
Glossary: cholesterol = cholest-5-en-3β-ol
Other name(s): cholesterol 25-hydroxylase (ambiguous)
Systematic name: cholesterol,hydrogen-donor:oxygen oxidoreductase (25-hydroxylating)
Comments: Unlike most other sterol hydroxylases, this enzyme is not a cytochrome P-450. Instead, it uses diiron cofactors to catalyse the hydroxylation of hydrophobic substrates [1]. The diiron cofactor can be either Fe-O-Fe or Fe-OH-Fe and is bound to the enzyme through interactions with clustered histidine or glutamate residues [4,5]. In cell cultures, this enzyme down-regulates cholesterol synthesis and the processing of sterol regulatory element binding proteins (SREBPs). cf. EC 1.17.99.10, cholesterol C-25 hydroxylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 60202-07-5
References:
1. Lund, E.G., Kerr, T.A., Sakai, J., Li, W.P. and Russell, D.W. cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism. J. Biol. Chem. 273 (1998) 34316-34327. [PMID: 9852097]
2. Chen, J.J., Lukyanenko, Y. and Hutson, J.C. 25-Hydroxycholesterol is produced by testicular macrophages during the early postnatal period and influences differentiation of Leydig cells in vitro. Biol. Reprod. 66 (2002) 1336-1341. [PMID: 11967195]
3. Lukyanenko, Y., Chen, J.J. and Hutson, J.C. Testosterone regulates 25-hydroxycholesterol production in testicular macrophages. Biol. Reprod. 67 (2002) 1435-1438. [PMID: 12390873]
4. Fox, B.G., Shanklin, J., Ai, J., Loehr, T.M. and Sanders-Loehr, J. Resonance Raman evidence for an Fe-O-Fe center in stearoyl-ACP desaturase. Primary sequence identity with other diiron-oxo proteins. Biochemistry 33 (1994) 12776-12786. [PMID: 7947683]
5. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]