Cholesterol 25-hydroxylase

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Cholesterol 25-hydroxylase
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EC no. 1.14.99.38
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In enzymology, a cholesterol 25-hydroxylase (EC 1.14.99.38) is an enzyme that catalyzes the chemical reaction

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]

Related Research Articles

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<span class="mw-page-title-main">GPR183</span> Protein-coding gene in the species Homo sapiens

G-protein coupled receptor 183 also known as Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) is a protein (GPCR) expressed on the surface of some immune cells, namely B cells and T cells; in humans it is encoded by the GPR183 gene. Expression of EBI2 is one critical mediator of immune cell localization within lymph nodes, responsible in part for the coordination of B cell, T cell, and dendritic cell movement and interaction following antigen exposure. EBI2 is a receptor for oxysterols. The most potent activator is 7α,25-dihydroxycholesterol (7α,25-OHC), with other oxysterols exhibiting varying affinities for the receptor. Oxysterol gradients drive chemotaxis, attracting the EBI2-expressing cells to locations of high ligand concentration. The GPR183 gene was identified due to its upregulation during Epstein-Barr virus infection of the Burkitt's lymphoma cell line BL41, hence its name: EBI2.

<span class="mw-page-title-main">CYP7B1</span> Protein-coding gene in the species Homo sapiens

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24<i>S</i>-Hydroxycholesterol Chemical compound

24S-Hydroxycholesterol (24S-HC), also known as cholest-5-ene-3,24-diol or cerebrosterol, is an endogenous oxysterol produced by neurons in the brain to maintain cholesterol homeostasis. It was discovered in 1953 by Alberto Ercoli, S. Di Frisco, and Pietro de Ruggieri, who first isolated the molecule in the horse brain and then demonstrated its presence in the human brain.

<span class="mw-page-title-main">25-Hydroxycholesterol</span> Chemical compound

25-Hydroxycholesterol is a chemical compound, a derivative of cholesterol, that plays a role in various biological processes in humans and other species. It is involved in cholesterol metabolism, antivirus process, inflammatory and immune response, and survival signaling pathway. 25-hydroxycholesterol is biosynthesized from cholesterol by adding a hydroxyl group at position 25-carbon of a steroid nucleus. This reaction is catalyzed by cholesterol 25-hydroxylase, a family of enzymes that use oxygen and a di-iron cofactor to catalyze hydroxylation reaction.

References

  1. 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.
  2. Limbad, Chandani; Doi, Ryosuke; McGirr, Julia; Ciotlos, Serban; Perez, Kevin; Clayton, Zachary S.; Daya, Radha; Seals, Douglas R.; Campisi, Judith; Melov, Simon (February 2022). "Senolysis induced by 25-hydroxycholesterol targets CRYAB in multiple cell types". iScience. 25 (2): 103848. doi:10.1016/j.isci.2022.103848. PMC   8851282 . PMID   35198901. S2CID   246502031.

Further reading