CYP46A1
Function
P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain. Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholesterol diffusion out of neurons and its further degradation (PubMed:10377398, PubMed:14640697, PubMed:18621681, PubMed:25017465). By promoting constant cholesterol elimination in neurons, may activate the mevalonate pathway and coordinate the synthesis of new cholesterol and nonsterol isoprenoids involved in synaptic activity and learning (By similarity). Further hydroxylates cholesterol derivatives and hormone steroids on both the ring and side chain of these molecules, converting them into active oxysterols involved in lipid signaling and biosynthesis (PubMed:12077124, PubMed:14640697, PubMed:28190002). Acts as an epoxidase converting cholesta-5,24-dien-3beta-ol/desmosterol into (24S),25-epoxycholesterol, an abundant lipid ligand of nuclear NR1H2 and NR1H3 receptors shown to promote neurogenesis in developing brain (PubMed:25017465). May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole (PubMed:20667828).
Pathway
Steroid metabolism; cholesterol degradation.
Lipid metabolism; C21-steroid hormone metabolism.
Sequence Similarities
Belongs to the cytochrome P450 family.
Tissue Specificity
Expressed in brain. The mRNA was broadly distributed with higher levels in gray matter zones and lower levels in regions rich in white matter. Not detected in fetal sample but its expression increases linearly with age.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass membrane protein
- Microsome membrane
- Single-pass membrane protein
- Postsynapse
- Presynapse
- Cell projection
- Dendrite
Alternative names
CYP46, CYP46A1, Cholesterol 24-hydroxylase, CH24H, Cholesterol 24-monooxygenase, Cholesterol 24S-hydroxylase, Cytochrome P450 46A1