CYP3A4
CYP3A4 (cytochrome P450 family 3 subfamily A member 4, also known as CYP3A3) is a membrane-bound cytochrome P450 monooxygenase of the endoplasmic reticulum. It oxidises steroids, retinoids, fatty acids and xenobiotics, and is involved in the metabolism of approximately half the drugs in use today. Browse Assay Genie's current range of CYP3A4 research reagents below, or read on for the biology behind the target.
CYP3A4 is a cytochrome P450 monooxygenase that catalyses the hydroxylation of carbon-hydrogen bonds. Mechanistically, it uses molecular oxygen, inserting one oxygen atom into the substrate and reducing the second to water, with two electrons supplied by NADPH through cytochrome P450 reductase (NADPH--hemoprotein reductase). Its endogenous substrates include sterols, steroid hormones, retinoids and fatty acids. It forms 2-hydroxy and C-16 hydroxylated derivatives of estrone and 17beta-estradiol, and deactivates testosterone by converting it to the less active 2beta- and 6beta-hydroxytestosterones.
The enzyme also contributes to the formation of oxysterols, including 4beta- and 25-hydroxycholesterol, which is likely to contribute to cholesterol degradation and bile acid biosynthesis. It hydroxylates and epoxidises polyunsaturated fatty acids, metabolises the endocannabinoid anandamide to epoxyeicosatrienoic acid ethanolamides, and oxidises all-trans-retinol to all-trans-retinal, a rate-limiting step in all-trans-retinoic acid biosynthesis. It further metabolises retinoic acid to 4-hydroxyretinoate and may take part in hepatic clearance. It is also involved in vitamin D catabolism and calcium homeostasis, inactivating calcitriol.
Among xenobiotics, CYP3A4 metabolises the majority of administered drugs, including acetaminophen, codeine, cyclosporin A, diazepam, erythromycin and chloroquine, as well as albendazole, fenbendazole and quinine. It also acts on some carcinogens and on plant compounds such as 1,8-cineole. The CYP3A4 gene lies in a cluster of cytochrome P450 genes on chromosome 7q, and its expression is induced by glucocorticoids and some pharmacological agents. The former symbol CYP3A3 is now thought to represent a transcript variant of CYP3A4, and alternative splicing yields different isoforms. The protein belongs to the cytochrome P450 family and the HGNC cytochrome P450 family 3 gene group.
CYP3A4 is involved in the metabolism of approximately half the drugs in use today, making it central to studies of drug clearance.
The enzyme hydroxylates estrone and 17beta-estradiol and deactivates testosterone, linking it to steroid hormone turnover.
CYP3A4 oxidises all-trans-retinol, metabolises retinoic acid and inactivates calcitriol, so it is relevant to retinoid and calcium homeostasis studies.
Its roles in oxysterol formation, bile acid biosynthesis and polyunsaturated fatty acid oxidation make it a target in lipid metabolism research.
CYP3A4 is a cytochrome P450 monooxygenase that inserts an oxygen atom into substrates using electrons from NADPH via cytochrome P450 reductase. It metabolises steroids, retinoids, fatty acids, oxysterols and most administered drugs, and also contributes to vitamin D catabolism.
CYP3A3 is a previous symbol listed as an alias of CYP3A4. It was once thought to be a separate gene, but the sequence is now thought to represent a transcript variant of CYP3A4. Alternatively spliced transcripts encoding different isoforms have also been identified.
CYP3A4 is involved in the metabolism of approximately half the drugs in use today, including acetaminophen, codeine, cyclosporin A, diazepam, erythromycin and chloroquine. Its expression is induced by glucocorticoids and some pharmacological agents. Check the datasheet of any product for its validated reactivity.
Other cytochrome P450 enzymes involved in drug, steroid, retinoid and vitamin D metabolism with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P08684; product specifications from Assay Genie datasheets.