{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox gene}}
'''Cytochrome P450 4F12''' is a protein that, in humans, is encoded by the ''CYP4F12'' gene.<ref name="Bylund_2001">{{cite journal | vauthors = Bylund J, Bylund M, Oliw EH | title = cDna cloning and expression of CYP4F12, a novel human cytochrome P450 | journal = Biochemical and Biophysical Research Communications | volume = 280 | issue = 3 | pages = 892–897 | date = Feb 2001 | pmid = 11162607 | doi = 10.1006/bbrc.2000.4191 | bibcode = 2001BBRC..280..892B }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CYP4F12 cytochrome P450, family 4, subfamily F, polypeptide 12 | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=66002 }}</ref>
== Gene family == The ''CYP4F12'' gene encodes a member of the cytochrome P450 superfamily of enzymes. It is located within a cluster of P450 genes on chromosome 19.<ref name="entrez" /><ref name="Arch Biochem Biophys p 15">{{cite journal | vauthors = Stark K, Wongsud B, Burman R, Oliw EH | title = Oxygenation of polyunsaturated long chain fatty acids by recombinant CYP4F8 and CYP4F12 and catalytic importance of Tyr-125 and Gly-328 of CYP4F8 | journal = Archives of Biochemistry and Biophysics | volume = 441 | issue = 2 | pages = 174–181 | date = September 2005 | pmid = 16112640 | doi = 10.1016/j.abb.2005.07.003 }}</ref> Cytochrome P450 proteins are monooxygenases that catalyze a wide array of reactions involved in drug metabolism and in the synthesis of cholesterol, steroids, and other lipids.
== Expression and localization == CYP4F12 is thought to localize to the endoplasmic reticulum. It is expressed in the liver and throughout the gastrointestinal tract. The enzyme is known to metabolize the antihistamines ebastine and terfenadine, suggesting it may play a role in the metabolism of these and other drugs.<ref name="Arch Biochem Biophys p 15" /><ref name="Johnson_2015">{{cite book | vauthors = Johnson AL, Edson KZ, Totah RA, Rettie AE | title = Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer | chapter = Cytochrome P450 ω-Hydroxylases in Inflammation and Cancer | series = Advances in Pharmacology | location = San Diego, Calif. | volume = 74 | pages = 223–262 | date = January 2015 | pmid = 26233909 | pmc = 4667791 | doi = 10.1016/bs.apha.2015.05.002 | isbn = 978-0-12-803119-3 }}</ref>
== Substrate specificity == When expressed in yeast, CYP4F12 oxidizes arachidonic acid by hydroxylating carbon 18 or 19 to form 18-HETE or 19-HETE, respectively, though the physiological significance of this activity remains unclear. It also metabolizes prostaglandin H2 (PGH2) and PGH1 to their 19-hydroxyl analogs, potentially reducing their biological activity.<ref name="Johnson_2015" />
In addition to monooxygenase activity, CYP4F12 also functions as an epoxygenase. It metabolizes docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two omega-3 fatty acids, to produce epoxide derivatives: DHA → 19''R'',20''S''- and 19''S'',20''R''-epoxydocosapentaenoic acids (19,20-EDP) EPA → 17''R'',18''S''- and 17''S'',18''R''-epoxyeicosatetraenoic acids (17,18-EEQ).<ref name="Westphal_2011">{{cite journal | vauthors = Westphal C, Konkel A, Schunck WH | title = CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease? | journal = Prostaglandins & Other Lipid Mediators | volume = 96 | issue = 1–4 | pages = 99–108 | date = November 2011 | pmid = 21945326 | doi = 10.1016/j.prostaglandins.2011.09.001 | doi-access = free }}</ref>
== Function == 19-HETE, one of CYP4F12’s products, inhibits the activity of 20-HETE, a pro-inflammatory and vasoconstrictive signaling molecule. However, the in vivo importance of this inhibition has yet to be confirmed (see 20-Hydroxyeicosatetraenoic acid). EDPs (see Epoxydocosapentaenoic acid) and EEQs (see epoxyeicosatetraenoic acid) exhibit a wide range of biological activities in animal models and in vitro systems: * Lower blood pressure<ref name="Fleming_2014">{{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 = 1106–1140 | date = October 2014 | pmid = 25244930 | doi = 10.1124/pr.113.007781 | s2cid = 39465144 }}</ref> and pain perception<ref name = "Zhang_2014">{{cite journal | vauthors = Zhang G, Kodani S, Hammock BD | title = Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer | journal = Progress in Lipid Research | volume = 53 | pages = 108–123 | date = January 2014 | pmid = 24345640 | pmc = 3914417 | doi = 10.1016/j.plipres.2013.11.003 }}</ref><ref name="Wagner_2014">{{cite journal | vauthors = Wagner K, Vito S, Inceoglu B, Hammock BD | title = The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling | journal = Prostaglandins & Other Lipid Mediators | volume = 113–115 | pages = 2–12 | date = October 2014 | pmid = 25240260 | pmc = 4254344 | doi = 10.1016/j.prostaglandins.2014.09.001 }}</ref> * Suppress inflammation<ref name = "Zhang_2014" /> * Inhibit angiogenesis, endothelial cell migration and proliferation]<ref name = "Zhang_2014" /> * Inhibit growth and metastasis of breast and prostate cancer cell lines]<ref name = "Zhang_2014" />
These findings suggest that EDPs and EEQs may contribute to the beneficial effects of dietary omega-3 fatty acids such as DHA and EPA in humans.<ref name="Fleming_2014" /><ref name="Wagner_2014" /><ref>{{cite journal | vauthors = Fischer R, Konkel A, Mehling H, Blossey K, Gapelyuk A, Wessel N, von Schacky C, Dechend R, Muller DN, Rothe M, Luft FC, Weylandt K, Schunck WH | title = Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway | journal = Journal of Lipid Research | volume = 55 | issue = 6 | pages = 1150–1164 | date = March 2014 | pmid = 24634501 | pmc = 4031946 | doi = 10.1194/jlr.M047357 | doi-access = free }}</ref><ref name = "He_2015">{{cite journal | vauthors = He J, Wang C, Zhu Y, Ai D | title = Soluble epoxide hydrolase: A potential target for metabolic diseases | journal = Journal of Diabetes | volume = 8 | issue = 3 | pages = 305–313 | date = December 2015 | pmid = 26621325 | doi = 10.1111/1753-0407.12358 | doi-access = free }}</ref> These metabolites are short-lived and are rapidly inactivated by epoxide hydrolases, particularly soluble epoxide hydrolase, limiting their action to local environments.
== Comparison with CYP4F8 == CYP4F12 shares similar enzymatic activity with CYP4F8, particularly in fatty acid metabolism and epoxide formation. However, neither enzyme is considered a major contributor to these processes in humans, although they may play important roles in tissues where they are highly expressed.<ref name="Johnson_2015" />
==References== {{reflist}}
==External links== * {{UCSC gene info|CYP4F12}}
==Further reading== {{refbegin | 2}} * {{cite journal | vauthors = Simpson AE | title = The cytochrome P450 4 (CYP4) family | journal = General Pharmacology | volume = 28 | issue = 3 | pages = 351–359 | date = Mar 1997 | pmid = 9068972 | doi = 10.1016/S0306-3623(96)00246-7 }} * {{cite journal | vauthors = Knight JA, Fronk S, Haymond RE | title = Chemical basis and specificity of chemical screening tests for urinary vanilmandelic acid | journal = Clinical Chemistry | volume = 21 | issue = 1 | pages = 130–133 | date = Jan 1975 | pmid = 1116264 | doi = 10.1093/clinchem/21.1.130 | doi-access = free }} * {{cite journal | vauthors = Hashizume T, Imaoka S, Hiroi T, Terauchi Y, Fujii T, Miyazaki H, Kamataki T, Funae Y | title = cDNA cloning and expression of a novel cytochrome p450 (cyp4f12) from human small intestine | journal = Biochemical and Biophysical Research Communications | volume = 280 | issue = 4 | pages = 1135–1141 | date = Feb 2001 | pmid = 11162645 | doi = 10.1006/bbrc.2000.4238 | bibcode = 2001BBRC..280.1135H }} * {{cite journal | vauthors = Stark K, Wongsud B, Burman R, Oliw EH | title = Oxygenation of polyunsaturated long chain fatty acids by recombinant CYP4F8 and CYP4F12 and catalytic importance of Tyr-125 and Gly-328 of CYP4F8 | journal = Archives of Biochemistry and Biophysics | volume = 441 | issue = 2 | pages = 174–181 | date = Sep 2005 | pmid = 16112640 | doi = 10.1016/j.abb.2005.07.003 }} * {{cite journal | vauthors = Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T | title = Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries | journal = DNA Research | volume = 12 | issue = 2 | pages = 117–126 | year = 2007 | pmid = 16303743 | doi = 10.1093/dnares/12.2.117 | doi-access = free }} * {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = Jan 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }} {{refend}} {{Cytochrome P450}}
Category:Cytochrome P450