CYP46A1
CYP46A1 (cytochrome P450 family 46 subfamily A member 1, also known as CYP46 or cholesterol 24-hydroxylase) is an endoplasmic reticulum monooxygenase expressed in the brain. It converts cholesterol to 24S-hydroxycholesterol and plays a major role in cerebral cholesterol homeostasis. Browse Assay Genie's current range of CYP46A1 research reagents below, or read on for the biology behind the target.
CYP46A1 is a P450 monooxygenase that primarily catalyses hydroxylation, with S stereochemistry, at C-24 of the cholesterol side chain. This step triggers cholesterol diffusion out of neurons and its further degradation. Cholesterol cannot pass the blood-brain barrier, but 24S-hydroxycholesterol can be secreted from the brain into the circulation and returned to the liver for catabolism. By promoting constant cholesterol elimination in neurons, CYP46A1 may activate the mevalonate pathway and coordinate the synthesis of new cholesterol and nonsterol isoprenoids involved in synaptic activity and learning.
The enzyme also hydroxylates cholesterol derivatives and hormone steroids on both the ring and side chain, converting them into active oxysterols involved in lipid signalling and biosynthesis. It acts as an epoxidase, converting desmosterol (cholesta-5,24-dien-3beta-ol) into (24S),25-epoxycholesterol, an abundant lipid ligand of the nuclear receptors NR1H2 and NR1H3 that has been shown to promote neurogenesis in the developing brain. CYP46A1 may also catalyse the oxidative metabolism of xenobiotics such as clotrimazole.
The CYP46A1 gene encodes a member of the cytochrome P450 superfamily, whose monooxygenases catalyse many reactions in drug metabolism and in the synthesis of cholesterol, steroids and other lipids. HGNC places it in the cytochrome P450 family 46 gene group, and earlier names include cytochrome P450, subfamily 46 (cholesterol 24-hydroxylase). UniProt annotates the protein at the endoplasmic reticulum and microsome membrane, and at the presynapse, postsynapse and dendrites. The mouse ortholog is Cyp46a1.
CYP46A1 plays a major role in cholesterol homeostasis in the brain, making it a central enzyme for studying cerebral sterol turnover.
The enzyme produces active oxysterols, including 24S-hydroxycholesterol, that are involved in lipid signalling and biosynthesis.
Through (24S),25-epoxycholesterol and the mevalonate pathway, CYP46A1 is linked to neurogenesis and to isoprenoids involved in synaptic activity and learning.
As a cytochrome P450, CYP46A1 may catalyse oxidative metabolism of xenobiotics such as clotrimazole, relevant to P450 drug metabolism studies.
CYP46A1 is a brain-expressed P450 monooxygenase that hydroxylates cholesterol at C-24 to form 24S-hydroxycholesterol. This lets cholesterol leave neurons and enter the circulation for hepatic catabolism, and may also regulate the mevalonate pathway in neurons.
The protein is also called cholesterol 24-hydroxylase, and CYP46 is a listed alias. HGNC previously named it cytochrome P450, subfamily 46 (cholesterol 24-hydroxylase). Its enzyme classification is EC 1.14.14.25. It belongs to the cytochrome P450 family.
A mouse ortholog, Cyp46a1, is recognised, so the enzyme can be studied in mouse models. Cross-species use of any reagent depends on sequence and validation, so check the datasheet of any product for its validated reactivity.
Other cytochrome P450 enzymes involved in cholesterol, steroid and xenobiotic metabolism with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9Y6A2; product specifications from Assay Genie datasheets.