In enzymology, a cholesterol 25-hydroxylase (EC 1.14.99.38) is an enzyme that catalyzes the chemical reaction
| Cholesterol 25-hydroxylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 1.14.99.38 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
- cholesterol + AH2 + O2 25-hydroxycholesterol + A + H2O
The 3 substrates of this enzyme are cholesterol, an electron acceptor AH2, and O2, whereas its 3 products are 25-hydroxycholesterol (25HC), the reduction product A, and H2O.
This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derive from O miscellaneous. The systematic name of this enzyme class is cholesterol, hydrogen-donor:oxygen oxidoreductase (25-hydroxylating). This enzyme is also called cholesterol 25-monooxygenase.
Transcripts for this enzyme have been identified in macrophages from the testis.
CH25H is an interferon-stimulated gene, and its primary product 25HC may have broad-spectrum antiviral activity, demonstrated in mice against HIV, ebola, Nipah virus, Rift Valley Fever virus, and SARS-CoV-2. Specifically, 25HC blocks membrane fusion between the cell and virus, and may "implicate membrane-modifying oxysterols as potential antiviral therapeutics.” Recently, upregulation of CH25H has been shown to play a role in effectively restricting infection of lung epithelial cells with SARS-Cov-2 through its enzymatic product, 25HC, which depletes accessible membrane cholesterol so that the virus is unable to achieve fusion with the cell membrane necessary for entry and infection.[1]
It has been proposed, based on experimental research in both mice and human cell culture, that 25HC is a potent senolytic. Further research needs to elaborate on this research and reveal its true significance to aging.[2]
References
edit- ^ Wang S, Li W, Hui H, Tiwari SK, Zhang Q, Croker BA, et al. (November 2020). "Cholesterol 25-Hydroxylase inhibits SARS-CoV-2 and other coronaviruses by depleting membrane cholesterol". The EMBO Journal. 39 (21): e106057. doi:10.15252/embj.2020106057. PMC 7537045. PMID 32944968.
- ^ Limbad C, Doi R, McGirr J, Ciotlos S, Perez K, Clayton ZS, Daya R, Seals DR, Campisi J, Melov S (February 2022). "Senolysis induced by 25-hydroxycholesterol targets CRYAB in multiple cell types". iScience. 25 (2): 103848. Bibcode:2022iSci...25j3848L. doi:10.1016/j.isci.2022.103848. PMC 8851282. PMID 35198901. S2CID 246502031.
Further reading
edit- Lund EG, Kerr TA, Sakai J, Li WP, Russell DW (December 1998). "cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism". The Journal of Biological Chemistry. 273 (51): 34316–27. doi:10.1074/jbc.273.51.34316. PMID 9852097.
- Chen JJ, Lukyanenko Y, Hutson JC (May 2002). "25-hydroxycholesterol is produced by testicular macrophages during the early postnatal period and influences differentiation of Leydig cells in vitro". Biology of Reproduction. 66 (5): 1336–41. doi:10.1095/biolreprod66.5.1336. PMID 11967195. S2CID 22637279.
- Lukyanenko Y, Chen JJ, Hutson JC (November 2002). "Testosterone regulates 25-hydroxycholesterol production in testicular macrophages". Biology of Reproduction. 67 (5): 1435–8. doi:10.1095/biolreprod.102.007575. PMID 12390873.
- Fox BG, Shanklin J, Ai J, Loehr TM, Sanders-Loehr J (November 1994). "Resonance Raman evidence for an Fe-O-Fe center in stearoyl-ACP desaturase. Primary sequence identity with other diiron-oxo proteins". Biochemistry. 33 (43): 12776–86. doi:10.1021/bi00209a008. PMID 7947683.
- Russell DW (2003). "The enzymes, regulation, and genetics of bile acid synthesis". Annual Review of Biochemistry. 72: 137–74. doi:10.1146/annurev.biochem.72.121801.161712. PMID 12543708.
