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'''Cytochrome P<sub>450</sub>2C8''' (abbreviated '''CYP2C8'''), a member of the [[cytochrome P450]] mixed-function oxidase system, is involved in the metabolism of [[xenobiotic]]s in the body.  Cytochrome P<sub>450</sub>2C8 also possesses [[epoxygenase]] activity, i.e. it metabolizes long-chain [[polyunsaturated fatty acids]], e.g. [[arachidonic acid]], [[eicosapentaenoic acid]], [[docosahexaenoic acid]], and [[Linoleic acid]] to their biologically active [[epoxide]]s.<ref>{{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 = Nov 2011 | pmid = 21945326 | doi = 10.1016/j.prostaglandins.2011.09.001 }}</ref>
{{EH}}


'''Cytochrome P<sub>450</sub>2C8''' (abbreviated '''CYP2C8'''), a member of the [[cytochrome P450]] mixed-function oxidase system, is involved in the metabolism of [[xenobiotic]]s in the body.
== CYP2C8 ligands ==
Following is a table of selected [[enzyme substrate|substrates]], [[enzyme induction and inhibition|inducers]] and [[enzyme induction and inhibition|inhibitors]] of 2C8.
 
Inhibitors of CYP2C8 can be classified by their [[potency (pharmacology)|potency]], such as:
*'''Strong inhibitor''' being one that causes at least a five-fold increase in the plasma [[area under the curve (pharmacokinetics)|AUC values]], or more than 80% decrease in [[clearance (medicine)|clearance]].<ref name=Flockhart/>
*'''Moderate inhibitor''' being one that causes at least a two-fold increase in the plasma AUC values, or 50-80% decrease in clearance.<ref name=Flockhart/>
*'''Weak inhibitor''' being one that causes at least a 1.25-fold but less than two-fold increase in the plasma AUC values, or 20-50% decrease in clearance.<ref name=Flockhart>{{cite web |author=Flockhart DA |title=Drug Interactions: Cytochrome P<sub>450</sub> Drug Interaction Table |publisher=[[Indiana University School of Medicine]] |year=2007 |url=http://medicine.iupui.edu/flockhart/table.htm}} Retrieved on July 2011</ref>


== CYP2C8 Ligands ==
{| class="wikitable"
{| class="wikitable"
|+'''Selected inducers, inhibitors and substrates of CYP2C8<ref>Where classes of agents are listed, there may be exceptions within the class</ref>'''
|+'''Selected inducers, inhibitors and substrates of CYP2C8'''
|-
|-
! Substrates !! Inhibitors !! Inducers
! Substrates !! Inhibitors !! Inducers
|- style="vertical-align: top;"
|- style="vertical-align: top;"
|  
| <!--Substrates-->
* [[cerivastatin]] ([[statin]])
* [[amodiaquine]]<ref name=Flockhart/> ([[antimalarial]], [[anti-inflammatory]])
* [[paclitaxel]] ([[chemotherapeutic]])
* [[cerivastatin]]<ref name=Flockhart/> ([[statin]])
* [[repaglinide]] ([[antidiabetic]])
* [[enzalutamide]] ([[antiandrogen]])
* [[torasemide]] ([[loop diuretic]])
* [[paclitaxel]]<ref name=Flockhart/> ([[chemotherapeutic]])
* [[ibuprofen]] ([[NSAID]])
* [[repaglinide]]<ref name=Flockhart/> ([[antidiabetic]])
* [[torasemide]]<ref name=Flockhart/> ([[loop diuretic]])
* [[sorafenib]]<ref name=Flockhart/> ([[tyrosine kinase]] inhibitor)
* [[rosiglitazone]] ([[antidiabetic]]) - converted to active metabolites<ref>Chapter 26 in: {{cite book |author1=Rod Flower |author2=Humphrey P. Rang |author3=Maureen M. Dale |author4=Ritter, James M. |title=Rang & Dale's pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2007 |pages= |isbn=0-443-06911-5 |oclc= |doi= |accessdate=}}</ref>
* [[buprenorphine]] (semisynthetic [[opioid]])
* [[polyunsaturated fatty acids]]
* [[montelukast]] ([[leukotriene receptor antagonist]])
||
 
'''Strong'''<!--Inhibitors-->
* [[gemfibrozil]]<ref name=Flockhart/> ([[hypolipidemic]])
 
'''Moderate'''<!--Inhibitors-->
* [[trimethoprim]]<ref name=Flockhart/> ([[antibiotic]])


||
'''<!--Inhibitors of-->Unspecified potency'''
* [[gemfibrozil]] ([[hypolipidemic]])
* [[thiazolidinedione]]s<ref name=Flockhart/> ([[antidiabetic]])
* [[thiazolidinedione]]s ([[antidiabetic]])
* [[montelukast]]<ref name=Flockhart/> ([[leukotriene receptor antagonist]])
** [[rosiglitazone]]
* [[quercetin]]<ref name=Flockhart/> ([[antiinflammatory]])
** [[pioglitazone]]
||
* [[montelukast]] ([[leukotriene receptor antagonist]])
* [[quercetin]] ([[antiinflammatory]])
* [[trimethoprim]] ([[antibiotic]])


|| 
'''<!--Inducers of-->Unspecified potency'''
* [[rifampicin]] ([[antibiotic]])
* [[rifampicin]]<ref name=Flockhart/> ([[antibiotic]])
|-
|-
|}
|}
Where classes of agents are listed, there may be exceptions within the class.
== Epoxygenase activity ==
CYP2C8 also possesses [[epoxygenase]] activitiy: it is one of the principal enzymes responsible for attacking various long-chain polyunsaturated fatty acids at their double (i.e. [[alkene]]) bonds to form [[epoxide]] products that act as signaling agents. It metabolizes: '''1)''' [[arachidonic acid]] to various [[epoxyeicosatrienoic acid]]s (also termed EETs); '''2)''' [[linoleic acid]] to 9,10-epoxy octadecaenoic acids (also termed [[vernolic acid]], linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecaenoic (also termed [[coronaric acid]], linoleic acid 12,13-oxide, or isoleukotoxin); '''3)''' docosohexaenoic acid to various [[epoxydocosapentaenoic acid]]s (also termed EDPs); and '''4)''' [[eicosapentaenoic acid]] to various epoxyeicosatetraenoic acids (also termed EEQs).<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 }}</ref><ref>{{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 | doi = 10.1016/j.prostaglandins.2014.09.001 | pmc=4254344}}</ref><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 | doi = 10.1194/jlr.M047357 | pmc=4031946}}</ref>
Along with CYP2C8, [[CYP2C9]], [[CYP2C19]], [[CYP2J2]], and possibly [[CYP2S1]] are the main producers of EETs and, very likely, EEQs, EDPs, and the epoxides of linoleic acid.<ref name="Spector AA 2014">{{cite journal | vauthors = Spector AA, Kim HY | title = Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism | journal = Biochimica et Biophysica Acta | volume = 1851 | issue = 4 | pages = 356–65 | date = April 2015 | pmid = 25093613 | doi = 10.1016/j.bbalip.2014.07.020 | pmc=4314516}}</ref><ref>{{cite journal | vauthors = Shahabi P, Siest G, Meyer UA, Visvikis-Siest S | title = Human cytochrome P450 epoxygenases: variability in expression and role in inflammation-related disorders | journal = Pharmacology & Therapeutics | volume = 144 | issue = 2 | pages = 134–61 | date = November 2014 | pmid = 24882266 | doi = 10.1016/j.pharmthera.2014.05.011 }}</ref>


== See also ==
== See also ==
*[[Cytochrome P450 oxidase]]
*[[Cytochrome P450 oxidase]]
*[[Epoxygenase]]
== References ==
{{reflist|33em}}
==External links==
* {{UCSC gene info|CYP2C8}}


==References==
== Further reading ==
{{reflist}}
{{refbegin|33em}}
==Further reading==
* {{cite journal | vauthors = Goldstein JA, de Morais SM | title = Biochemistry and molecular biology of the human CYP2C subfamily | journal = Pharmacogenetics | volume = 4 | issue = 6 | pages = 285–99 | date = Dec 1994 | pmid = 7704034 | doi = 10.1097/00008571-199412000-00001 }}
{{refbegin | 2}}
* {{cite journal | vauthors = Smith G, Stubbins MJ, Harries LW, Wolf CR | title = Molecular genetics of the human cytochrome P450 monooxygenase superfamily | journal = Xenobiotica | volume = 28 | issue = 12 | pages = 1129–65 | date = Dec 1998 | pmid = 9890157 | doi = 10.1080/004982598238868 }}
{{PBB_Further_reading
* {{cite journal | vauthors = García-Martín E, Martínez C, Ladero JM, Agúndez JA | title = Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals | journal = Molecular Diagnosis & Therapy | volume = 10 | issue = 1 | pages = 29–40 | year = 2007 | pmid = 16646575 | doi = 10.1007/BF03256440 }}
| citations =
* {{cite journal | vauthors = Ged C, Beaune P | title = Isolation of the human cytochrome P-450 IIC8 gene: multiple glucocorticoid responsive elements in the 5' region | journal = Biochimica et Biophysica Acta | volume = 1088 | issue = 3 | pages = 433–5 | date = Mar 1991 | pmid = 1707679 | doi = 10.1016/0167-4781(91)90138-c }}
*{{cite journal | author=Goldstein JA, de Morais SM |title=Biochemistry and molecular biology of the human CYP2C subfamily. |journal=Pharmacogenetics |volume=4 |issue= 6 |pages= 285–99 |year= 1995 |pmid= 7704034 |doi=10.1097/00008571-199412000-00001 }}
* {{cite journal | vauthors = Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA | title = Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily | journal = Biochemistry | volume = 30 | issue = 13 | pages = 3247–55 | date = Apr 1991 | pmid = 2009263 | doi = 10.1021/bi00227a012 }}
*{{cite journal | author=Smith G, Stubbins MJ, Harries LW, Wolf CR |title=Molecular genetics of the human cytochrome P450 monooxygenase superfamily. |journal=Xenobiotica |volume=28 |issue= 12 |pages= 1129–65 |year= 1999 |pmid= 9890157 |doi=10.1080/004982598238868 }}
* {{cite journal | vauthors = Kolyada AY | title = Sequence of a human liver cytochrome P-450 cDNA clone | journal = Nucleic Acids Research | volume = 18 | issue = 18 | pages = 5550 | date = Sep 1990 | pmid = 2216732 | pmc = 332242 | doi = 10.1093/nar/18.18.5550 }}
*{{cite journal | author=García-Martín E, Martínez C, Ladero JM, Agúndez JA |title=Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals. |journal=Molecular diagnosis & therapy |volume=10 |issue= 1 |pages= 29–40 |year= 2007 |pmid= 16646575 |doi= }}
* {{cite journal | vauthors = Shephard EA, Phillips IR, Santisteban I, Palmer CN, Povey S | title = Cloning, expression and chromosomal localization of a member of the human cytochrome P450IIC gene sub-family | journal = Annals of Human Genetics | volume = 53 | issue = Pt 1 | pages = 23–31 | date = Jan 1989 | pmid = 2729895 | doi = 10.1111/j.1469-1809.1989.tb01119.x }}
*{{cite journal | author=Ged C, Beaune P |title=Isolation of the human cytochrome P-450 IIC8 gene: multiple glucocorticoid responsive elements in the 5' region. |journal=Biochim. Biophys. Acta |volume=1088 |issue= 3 |pages= 433–5 |year= 1991 |pmid= 1707679 |doi= }}
* {{cite journal | vauthors = Ged C, Umbenhauer DR, Bellew TM, Bork RW, Srivastava PK, Shinriki N, Lloyd RS, Guengerich FP | title = Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase | journal = Biochemistry | volume = 27 | issue = 18 | pages = 6929–40 | date = Sep 1988 | pmid = 3196692 | doi = 10.1021/bi00418a039 }}
*{{cite journal | author=Romkes M, Faletto MB, Blaisdell JA, ''et al.'' |title=Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily. |journal=Biochemistry |volume=30 |issue= 13 |pages= 3247–55 |year= 1991 |pmid= 2009263 |doi=10.1021/bi00227a012 }}
* {{cite journal | vauthors = Okino ST, Quattrochi LC, Pendurthi UR, McBride OW, Tukey RH | title = Characterization of multiple human cytochrome P-450 1 cDNAs. The chromosomal localization of the gene and evidence for alternate RNA splicing | journal = The Journal of Biological Chemistry | volume = 262 | issue = 33 | pages = 16072–9 | date = Nov 1987 | pmid = 3500169 | doi =  }}
*{{cite journal | author=Kolyada AY |title=Sequence of a human liver cytochrome P-450 cDNA clone. |journal=Nucleic Acids Res. |volume=18 |issue= 18 |pages= 5550 |year= 1990 |pmid= 2216732 |doi=10.1093/nar/18.18.5550 }}
* {{cite journal | vauthors = Kimura S, Pastewka J, Gelboin HV, Gonzalez FJ | title = cDNA and amino acid sequences of two members of the human P450IIC gene subfamily | journal = Nucleic Acids Research | volume = 15 | issue = 23 | pages = 10053–4 | date = Dec 1987 | pmid = 3697070 | pmc = 306558 | doi = 10.1093/nar/15.23.10053 }}
*{{cite journal | author=Shephard EA, Phillips IR, Santisteban I, ''et al.'' |title=Cloning, expression and chromosomal localization of a member of the human cytochrome P450IIC gene sub-family. |journal=Ann. Hum. Genet. |volume=53 |issue= Pt 1 |pages= 23–31 |year= 1989 |pmid= 2729895 |doi=10.1111/j.1469-1809.1989.tb01119.x }}
* {{cite journal | vauthors = Zeldin DC, DuBois RN, Falck JR, Capdevila JH | title = Molecular cloning, expression and characterization of an endogenous human cytochrome P450 arachidonic acid epoxygenase isoform | journal = Archives of Biochemistry and Biophysics | volume = 322 | issue = 1 | pages = 76–86 | date = Sep 1995 | pmid = 7574697 | doi = 10.1006/abbi.1995.1438 }}
*{{cite journal | author=Ged C, Umbenhauer DR, Bellew TM, ''et al.'' |title=Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase. |journal=Biochemistry |volume=27 |issue= 18 |pages= 6929–40 |year= 1989 |pmid= 3196692 |doi=10.1021/bi00418a039 }}
* {{cite journal | vauthors = Inoue K, Inazawa J, Suzuki Y, Shimada T, Yamazaki H, Guengerich FP, Abe T | title = Fluorescence in situ hybridization analysis of chromosomal localization of three human cytochrome P450 2C genes (CYP2C8, 2C9, and 2C10) at 10q24.1 | journal = The Japanese Journal of Human Genetics | volume = 39 | issue = 3 | pages = 337–43 | date = Sep 1994 | pmid = 7841444 | doi = 10.1007/BF01874052 }}
*{{cite journal | author=Okino ST, Quattrochi LC, Pendurthi UR, ''et al.'' |title=Characterization of multiple human cytochrome P-450 1 cDNAs. The chromosomal localization of the gene and evidence for alternate RNA splicing. |journal=J. Biol. Chem. |volume=262 |issue= 33 |pages= 16072–9 |year= 1987 |pmid= 3500169 |doi=  }}
* {{cite journal | vauthors = Gray IC, Nobile C, Muresu R, Ford S, Spurr NK | title = A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24 | journal = Genomics | volume = 28 | issue = 2 | pages = 328–32 | date = Jul 1995 | pmid = 8530044 | doi = 10.1006/geno.1995.1149 }}
*{{cite journal | author=Kimura S, Pastewka J, Gelboin HV, Gonzalez FJ |title=cDNA and amino acid sequences of two members of the human P450IIC gene subfamily. |journal=Nucleic Acids Res. |volume=15 |issue= 23 |pages= 10053–4 |year= 1988 |pmid= 3697070 |doi=10.1093/nar/15.23.10053 }}
* {{cite journal | vauthors = Wormhoudt LW, Ploemen JH, de Waziers I, Commandeur JN, Beaune PH, van Bladeren PJ, Vermeulen NP | title = Inter-individual variability in the oxidation of 1,2-dibromoethane: use of heterologously expressed human cytochrome P450 and human liver microsomes | journal = Chemico-Biological Interactions | volume = 101 | issue = 3 | pages = 175–92 | date = Sep 1996 | pmid = 8870687 | doi = 10.1016/0009-2797(96)03723-4 }}
*{{cite journal | author=Zeldin DC, DuBois RN, Falck JR, Capdevila JH |title=Molecular cloning, expression and characterization of an endogenous human cytochrome P450 arachidonic acid epoxygenase isoform. |journal=Arch. Biochem. Biophys. |volume=322 |issue= 1 |pages= 76–86 |year= 1995 |pmid= 7574697 |doi= 10.1006/abbi.1995.1438 }}
* {{cite journal | vauthors = McFayden MC, Melvin WT, Murray GI | title = Regional distribution of individual forms of cytochrome P450 mRNA in normal adult human brain | journal = Biochemical Pharmacology | volume = 55 | issue = 6 | pages = 825–30 | date = Mar 1998 | pmid = 9586955 | doi = 10.1016/S0006-2952(97)00516-9 }}
*{{cite journal | author=Inoue K, Inazawa J, Suzuki Y, ''et al.'' |title=Fluorescence in situ hybridization analysis of chromosomal localization of three human cytochrome P450 2C genes (CYP2C8, 2C9, and 2C10) at 10q24.1. |journal=Jpn. J. Hum. Genet. |volume=39 |issue= 3 |pages= 337–43 |year= 1995 |pmid= 7841444 |doi=10.1007/BF01874052 }}
* {{cite journal | vauthors = Macé K, Bowman ED, Vautravers P, Shields PG, Harris CC, Pfeifer AM | title = Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues | journal = European Journal of Cancer | volume = 34 | issue = 6 | pages = 914–20 | date = May 1998 | pmid = 9797707 | doi = 10.1016/S0959-8049(98)00034-3 }}
*{{cite journal | author=Gray IC, Nobile C, Muresu R, ''et al.'' |title=A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24. |journal=Genomics |volume=28 |issue= 2 |pages= 328–32 |year= 1996 |pmid= 8530044 |doi= 10.1006/geno.1995.1149 }}
* {{cite journal | vauthors = Klose TS, Blaisdell JA, Goldstein JA | title = Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs | journal = Journal of Biochemical and Molecular Toxicology | volume = 13 | issue = 6 | pages = 289–95 | year = 1999 | pmid = 10487415 | doi = 10.1002/(SICI)1099-0461(1999)13:6<289::AID-JBT1>3.0.CO;2-N }}
*{{cite journal | author=Wormhoudt LW, Ploemen JH, de Waziers I, ''et al.'' |title=Inter-individual variability in the oxidation of 1,2-dibromoethane: use of heterologously expressed human cytochrome P450 and human liver microsomes. |journal=Chem. Biol. Interact. |volume=101 |issue= 3 |pages= 175–92 |year= 1996 |pmid= 8870687 |doi=10.1016/0009-2797(96)03723-4 }}
* {{cite journal | vauthors = Finta C, Zaphiropoulos PG | title = The human CYP2C locus: a prototype for intergenic and exon repetition splicing events | journal = Genomics | volume = 63 | issue = 3 | pages = 433–8 | date = Feb 2000 | pmid = 10704292 | doi = 10.1006/geno.1999.6063 }}
*{{cite journal | author=McFayden MC, Melvin WT, Murray GI |title=Regional distribution of individual forms of cytochrome P450 mRNA in normal adult human brain. |journal=Biochem. Pharmacol. |volume=55 |issue= 6 |pages= 825–30 |year= 1998 |pmid= 9586955 |doi=10.1016/S0006-2952(97)00516-9 }}
*{{cite journal | author=Macé K, Bowman ED, Vautravers P, ''et al.'' |title=Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues. |journal=Eur. J. Cancer |volume=34 |issue= 6 |pages= 914–20 |year= 1998 |pmid= 9797707 |doi=10.1016/S0959-8049(98)00034-3 }}
*{{cite journal | author=Klose TS, Blaisdell JA, Goldstein JA |title=Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. |journal=J. Biochem. Mol. Toxicol. |volume=13 |issue= 6 |pages= 289–95 |year= 1999 |pmid= 10487415 |doi=10.1002/(SICI)1099-0461(1999)13:6<289::AID-JBT1>3.0.CO;2-N }}
*{{cite journal | author=Finta C, Zaphiropoulos PG |title=The human CYP2C locus: a prototype for intergenic and exon repetition splicing events. |journal=Genomics |volume=63 |issue= 3 |pages= 433–8 |year= 2000 |pmid= 10704292 |doi= 10.1006/geno.1999.6063 }}
}}
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{{refend}}
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[[Category:Cytochrome P450]]
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Latest revision as of 20:37, 9 May 2017

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Cytochrome P4502C8 (abbreviated CYP2C8), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-chain polyunsaturated fatty acids, e.g. arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and Linoleic acid to their biologically active epoxides.[1]

CYP2C8 ligands

Following is a table of selected substrates, inducers and inhibitors of 2C8.

Inhibitors of CYP2C8 can be classified by their potency, such as:

  • Strong inhibitor being one that causes at least a five-fold increase in the plasma AUC values, or more than 80% decrease in clearance.[2]
  • Moderate inhibitor being one that causes at least a two-fold increase in the plasma AUC values, or 50-80% decrease in clearance.[2]
  • Weak inhibitor being one that causes at least a 1.25-fold but less than two-fold increase in the plasma AUC values, or 20-50% decrease in clearance.[2]
Selected inducers, inhibitors and substrates of CYP2C8
Substrates Inhibitors Inducers

Strong

Moderate

Unspecified potency

Unspecified potency

Where classes of agents are listed, there may be exceptions within the class.

Epoxygenase activity

CYP2C8 also possesses epoxygenase activitiy: it is one of the principal enzymes responsible for attacking various long-chain polyunsaturated fatty acids at their double (i.e. alkene) bonds to form epoxide products that act as signaling agents. It metabolizes: 1) arachidonic acid to various epoxyeicosatrienoic acids (also termed EETs); 2) linoleic acid to 9,10-epoxy octadecaenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecaenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); 3) docosohexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and 4) eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs).[4][5][6]

Along with CYP2C8, CYP2C9, CYP2C19, CYP2J2, and possibly CYP2S1 are the main producers of EETs and, very likely, EEQs, EDPs, and the epoxides of linoleic acid.[7][8]

See also

References

  1. ↑ Westphal C, Konkel A, Schunck WH (Nov 2011). "CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?". Prostaglandins & Other Lipid Mediators. 96 (1–4): 99–108. doi:10.1016/j.prostaglandins.2011.09.001. PMID 21945326.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. Retrieved on July 2011
  3. ↑ Chapter 26 in: Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-06911-5.
  4. ↑ Fleming I (October 2014). "The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease". Pharmacological Reviews. 66 (4): 1106–40. doi:10.1124/pr.113.007781. PMID 25244930.
  5. ↑ Wagner K, Vito S, Inceoglu B, Hammock BD (October 2014). "The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling". Prostaglandins & Other Lipid Mediators. 113-115: 2–12. doi:10.1016/j.prostaglandins.2014.09.001. PMC 4254344. PMID 25240260.
  6. ↑ 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 (March 2014). "Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway". Journal of Lipid Research. 55 (6): 1150–1164. doi:10.1194/jlr.M047357. PMC 4031946. PMID 24634501.
  7. ↑ Spector AA, Kim HY (April 2015). "Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism". Biochimica et Biophysica Acta. 1851 (4): 356–65. doi:10.1016/j.bbalip.2014.07.020. PMC 4314516. PMID 25093613.
  8. ↑ Shahabi P, Siest G, Meyer UA, Visvikis-Siest S (November 2014). "Human cytochrome P450 epoxygenases: variability in expression and role in inflammation-related disorders". Pharmacology & Therapeutics. 144 (2): 134–61. doi:10.1016/j.pharmthera.2014.05.011. PMID 24882266.

External links

Further reading

  • Goldstein JA, de Morais SM (Dec 1994). "Biochemistry and molecular biology of the human CYP2C subfamily". Pharmacogenetics. 4 (6): 285–99. doi:10.1097/00008571-199412000-00001. PMID 7704034.
  • Smith G, Stubbins MJ, Harries LW, Wolf CR (Dec 1998). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica. 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.
  • García-Martín E, Martínez C, Ladero JM, Agúndez JA (2007). "Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals". Molecular Diagnosis & Therapy. 10 (1): 29–40. doi:10.1007/BF03256440. PMID 16646575.
  • Ged C, Beaune P (Mar 1991). "Isolation of the human cytochrome P-450 IIC8 gene: multiple glucocorticoid responsive elements in the 5' region". Biochimica et Biophysica Acta. 1088 (3): 433–5. doi:10.1016/0167-4781(91)90138-c. PMID 1707679.
  • Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA (Apr 1991). "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily". Biochemistry. 30 (13): 3247–55. doi:10.1021/bi00227a012. PMID 2009263.
  • Kolyada AY (Sep 1990). "Sequence of a human liver cytochrome P-450 cDNA clone". Nucleic Acids Research. 18 (18): 5550. doi:10.1093/nar/18.18.5550. PMC 332242. PMID 2216732.
  • Shephard EA, Phillips IR, Santisteban I, Palmer CN, Povey S (Jan 1989). "Cloning, expression and chromosomal localization of a member of the human cytochrome P450IIC gene sub-family". Annals of Human Genetics. 53 (Pt 1): 23–31. doi:10.1111/j.1469-1809.1989.tb01119.x. PMID 2729895.
  • Ged C, Umbenhauer DR, Bellew TM, Bork RW, Srivastava PK, Shinriki N, Lloyd RS, Guengerich FP (Sep 1988). "Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase". Biochemistry. 27 (18): 6929–40. doi:10.1021/bi00418a039. PMID 3196692.
  • Okino ST, Quattrochi LC, Pendurthi UR, McBride OW, Tukey RH (Nov 1987). "Characterization of multiple human cytochrome P-450 1 cDNAs. The chromosomal localization of the gene and evidence for alternate RNA splicing". The Journal of Biological Chemistry. 262 (33): 16072–9. PMID 3500169.
  • Kimura S, Pastewka J, Gelboin HV, Gonzalez FJ (Dec 1987). "cDNA and amino acid sequences of two members of the human P450IIC gene subfamily". Nucleic Acids Research. 15 (23): 10053–4. doi:10.1093/nar/15.23.10053. PMC 306558. PMID 3697070.
  • Zeldin DC, DuBois RN, Falck JR, Capdevila JH (Sep 1995). "Molecular cloning, expression and characterization of an endogenous human cytochrome P450 arachidonic acid epoxygenase isoform". Archives of Biochemistry and Biophysics. 322 (1): 76–86. doi:10.1006/abbi.1995.1438. PMID 7574697.
  • Inoue K, Inazawa J, Suzuki Y, Shimada T, Yamazaki H, Guengerich FP, Abe T (Sep 1994). "Fluorescence in situ hybridization analysis of chromosomal localization of three human cytochrome P450 2C genes (CYP2C8, 2C9, and 2C10) at 10q24.1". The Japanese Journal of Human Genetics. 39 (3): 337–43. doi:10.1007/BF01874052. PMID 7841444.
  • Gray IC, Nobile C, Muresu R, Ford S, Spurr NK (Jul 1995). "A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24". Genomics. 28 (2): 328–32. doi:10.1006/geno.1995.1149. PMID 8530044.
  • Wormhoudt LW, Ploemen JH, de Waziers I, Commandeur JN, Beaune PH, van Bladeren PJ, Vermeulen NP (Sep 1996). "Inter-individual variability in the oxidation of 1,2-dibromoethane: use of heterologously expressed human cytochrome P450 and human liver microsomes". Chemico-Biological Interactions. 101 (3): 175–92. doi:10.1016/0009-2797(96)03723-4. PMID 8870687.
  • McFayden MC, Melvin WT, Murray GI (Mar 1998). "Regional distribution of individual forms of cytochrome P450 mRNA in normal adult human brain". Biochemical Pharmacology. 55 (6): 825–30. doi:10.1016/S0006-2952(97)00516-9. PMID 9586955.
  • Macé K, Bowman ED, Vautravers P, Shields PG, Harris CC, Pfeifer AM (May 1998). "Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues". European Journal of Cancer. 34 (6): 914–20. doi:10.1016/S0959-8049(98)00034-3. PMID 9797707.
  • Klose TS, Blaisdell JA, Goldstein JA (1999). "Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs". Journal of Biochemical and Molecular Toxicology. 13 (6): 289–95. doi:10.1002/(SICI)1099-0461(1999)13:6<289::AID-JBT1>3.0.CO;2-N. PMID 10487415.
  • Finta C, Zaphiropoulos PG (Feb 2000). "The human CYP2C locus: a prototype for intergenic and exon repetition splicing events". Genomics. 63 (3): 433–8. doi:10.1006/geno.1999.6063. PMID 10704292.
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