CYP46A1

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein is expressed in the brain, where it converts cholesterol to 24S-hydroxycholesterol. While cholesterol cannot pass the blood-brain barrier, 24S-hydroxycholesterol can be secreted in the brain into the circulation to be returned to the liver for catabolism. [provided by RefSeq]

cytochrome P450, family 46, subfamily A, polypeptide 1

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:25017465, PubMed:18621681).

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).

Bile acid biosynthetic process Source: Reactome
Cholesterol catabolic process Source: UniProtKB
Nervous system development Source: ProtInc
Progesterone metabolic process Source: UniProtKB
Protein localization to membrane raft Source: ARUK-UCL
Regulation of long-term synaptic potentiation Source: UniProtKB
Sterol metabolic process Source: Reactome
Xenobiotic metabolic process Source: UniProtKB

Endoplasmic reticulum membrane; Microsome membrane; Postsynapse; Presynapse; Dendrite

Helical: 3-23