Editing CYP3A4 (section)

== Function ==
CYP3A4 is a member of the [[cytochrome P450]] [[superfamily (molecular biology)|superfamily]] of [[enzyme]]s. The cytochrome P450 proteins are [[monooxygenase]]s that catalyze many reactions involved in [[drug metabolism]] and synthesis of  [[steroid]]s (including [[cholesterol]]), and other [[lipid]]s.<ref name="refseq">{{NCBI RefSeq|title=CYP3A4 cytochrome P450 family 3 subfamily A member 4 [ Homo sapiens (human) ]|url=https://www.ncbi.nlm.nih.gov/gene/1576}}</ref>

The CYP3A4 protein localizes to the [[endoplasmic reticulum]], and its expression is induced by [[glucocorticoid]]s and some pharmacological agents.<ref name="refseq"/> Cytochrome P450 enzymes metabolize approximately 60% of prescribed drugs, with CYP3A4 responsible for about half of this metabolism;<ref>{{cite journal | vauthors = Zanger UM, Schwab M | title = Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation | journal = Pharmacology & Therapeutics | volume = 138 | issue = 1 | pages = 103–41 | date = April 2013 | pmid = 23333322 | doi = 10.1016/j.pharmthera.2012.12.007 | doi-access = free }}</ref> substrates include [[acetaminophen]] (paracetamol), [[codeine]], [[ciclosporin]] (cyclosporin), [[diazepam]], [[erythromycin]], and [[chloroquine]].<ref name="refseq"/> The enzyme also metabolizes some [[steroid]]s and [[carcinogen]]s.<ref name="entrez">{{EntrezGene|1576}}</ref> Most drugs undergo deactivation by CYP3A4, either directly or by facilitated [[excretion]] from the body. Also, many substances are [[bioactivation|bioactivated]] by CYP3A4 to form their active compounds, and many protoxins are [[toxicated]] into their toxic forms ''(see table below for examples)''.

CYP3A4 also possesses [[epoxygenase]] activity in that it metabolizes [[arachidonic acid]] to [[epoxyeicosatrienoic acid]]s (EETs), i.e. (±)-8,9-, (±)-11,12-, and (±)-14,15-epoxyeicosatrienoic acids.<ref>{{cite journal | vauthors = Bishop-Bailey D, Thomson S, Askari A, Faulkner A, Wheeler-Jones C | title = Lipid-metabolizing CYPs in the regulation and dysregulation of metabolism | journal = Annual Review of Nutrition | volume = 34 | pages = 261–79 | pmid = 24819323 | doi = 10.1146/annurev-nutr-071813-105747 | year = 2014 | url = https://rvc-repository.worktribe.com/preview/1659487/kura-et-al-2023-can-mass-drug-administration-of-moxidectin-accelerate-onchocerciasis-elimination-in-africa.pdf | access-date = 2 February 2024 | archive-date = 18 January 2024 | archive-url = https://web.archive.org/web/20240118040330/https://rvc-repository.worktribe.com/preview/1659487/kura-et-al-2023-can-mass-drug-administration-of-moxidectin-accelerate-onchocerciasis-elimination-in-africa.pdf | url-status = live }}</ref> EETs have a wide range of activities including the promotion of certain types of [[cancer]]s (see [[epoxyeicosatetraenoic acid#cancer|epoxyeicosatetraenoic acid]]). CYP3A4 promotes the growth of various types of human cancer cell lines in culture by producing (±)-14,15-epoxyeicosatrienoic acids, which stimulate these cells to grow.<ref>{{cite journal | vauthors = Fleming I | title = The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease | journal = Pharmacological Reviews | volume = 66 | issue = 4 | pages = 1106–40 | date = October 2014 | pmid = 25244930 | doi = 10.1124/pr.113.007781 | doi-access =  }}</ref>  The CYP3A4 enzyme is also reported to have fatty acid monooxgenase activity for metabolizing arachidonic acid to [[20-Hydroxyeicosatetraenoic acid]] (20-HETE).<ref name="pmid11375247">{{cite journal | vauthors = Miyata N, Taniguchi K, Seki T, Ishimoto T, Sato-Watanabe M, Yasuda Y, Doi M, Kametani S, Tomishima Y, Ueki T, Sato M, Kameo K | title = HET0016, a potent and selective inhibitor of 20-HETE synthesizing enzyme | journal = British Journal of Pharmacology | volume = 133 | issue = 3 | pages = 325–9 | date = June 2001 | pmid = 11375247 | pmc = 1572803 | doi = 10.1038/sj.bjp.0704101 }}</ref> 20-HETE has a wide range of activities that include growth stimulation in breast and other types of cancers (see [[12-hydroxyeicosatetraenoic acid#cancer|12-hydroxyeicosatetraenoic acid]]).