Human CH25H: Cholesterol 25-hydroxylation and regulatory oxysterol production Manual

Human CH25H: Cholesterol 25-hydroxylation and regulatory oxysterol production

Reference protein: O95992. This is a manual literature synthesis using fetched primary-publication text and the reviewed human UniProt record.

Enzyme identity

Cloning of human and mouse CH25H established a polytopic membrane enzyme that hydroxylates cholesterol at C25. Histidine clusters and a diiron cofactor distinguish it from cytochrome-P450 sterol hydroxylases. The reaction synthesizes an oxysterol while consuming cholesterol; these two descriptions are compatible. The product suppresses SREBP processing and downstream cholesterol biosynthesis. PMID:9852097(https://pubmed.ncbi.nlm.nih.gov/9852097/)

Antiviral mechanism

Human-cell and organoid experiments connect 25-hydroxycholesterol to inhibition of coronavirus membrane fusion. One study links the effect to ACAT activation and depletion of accessible plasma-membrane cholesterol; another emphasizes late-endosome accumulation and cholesterol-export blockade. These describe context-dependent consequences of the lipid product, not direct enzymatic destruction of virus proteins. PMID:32944968(https://pubmed.ncbi.nlm.nih.gov/32944968/)

Annotation specificity

Cholesterol 25-hydroxylase activity is a specific molecular function. Broad oxidoreductase activity is true but less informative. Lipid biosynthesis is not refuted by the product inhibiting cholesterol synthesis. C4 methylsterol oxidation and zymosterol synthesis require different chemistry and must not be transferred solely from shared sterol-enzyme family membership. Immune-cell chemotaxis roles are downstream of oxysterol metabolism. PMID:9852097(https://pubmed.ncbi.nlm.nih.gov/9852097/)

Conservation and limits

The target horse enzyme is nearly full length relative to human, unlike a clearly truncated targeting variant. Catalysis is a reasonable mammalian transfer. Cell-type induction, antiviral efficacy and immune-cell positioning should be marked as transferred or context-dependent rather than presented as horse measurements. PMID:33239446(https://pubmed.ncbi.nlm.nih.gov/33239446/)

Evidence access and research scope

The source caches distinguish full text from abstract-only access; unresolved experimental annotations should remain UNDECIDED until their supporting material is available. This synthesis focuses on the biochemical mechanism, localization, and evidence needed for the paired horse prediction assessment; it does not certify every existing GO annotation.