CYP2C8

CYP2C8
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCYP2C8, CPC8, CYPIIC8, MP-12/MP-20, cytochrome P450 family 2 subfamily C member 8, CYP2C8DM
External IDsOMIM: 601129; MGI: 1306818; HomoloGene: 117948; GeneCards: CYP2C8; OMA:CYP2C8 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1558

13098

Ensembl

ENSG00000138115

ENSMUSG00000025003

UniProt

P10632

P56656

RefSeq (mRNA)

NM_000770
NM_001198853
NM_001198854
NM_001198855
NM_030878

NM_010003
NM_001373937

RefSeq (protein)

NP_000761
NP_001185782
NP_001185783
NP_001185784

NP_034133
NP_001360866

Location (UCSC)Chr 10: 95.04 – 95.07 MbChr 19: 39.5 – 39.56 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cytochrome P4502C8 (CYP2C8) is a member of the cytochrome P450 mixed-function oxidase system 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.[5]

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.[6]
  • Moderate inhibitor being one that causes at least a two-fold increase in the plasma AUC values, or 50-80% decrease in clearance.[6]
  • 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.[6]
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 activity: 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 octadecenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); 3) docosahexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and 4) eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs).[9][10][11]

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.[12][13]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000138115 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025003 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ a b c d e f g h i j k l m n o Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. Archived from the original on 2007-10-10. Retrieved 2011-07-10. Retrieved on July 2011
  7. ^ Chapter 26 in: Rod Flower, Humphrey P. Rang, Maureen M. Dale, Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-06911-6.
  8. ^ Product Information: PLAVIX(R) oral tablets, clopidogrel bisulfate oral tablets. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership (per FDA), Bridgewater, NJ, 2019. https://packageinserts.bms.com/pi/pi_plavix.pdf Archived 2021-06-12 at the Wayback Machine
  9. ^ 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. S2CID 39465144.
  10. ^ 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.
  11. ^ 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.
  12. ^ Spector AA, Kim HY (April 2015). "Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1851 (4): 356–65. doi:10.1016/j.bbalip.2014.07.020. PMC 4314516. PMID 25093613.
  13. ^ 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.

Further reading