Biology:CYP2C8

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Short description: Gene-coded protein involved in metabolism of xenobiotics


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


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.[1]

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 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).[5][6][7]

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.[8][9]

See also

References

  1. ↑ "CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?". Prostaglandins & Other Lipid Mediators 96 (1–4): 99–108. Nov 2011. 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. http://medicine.iupui.edu/flockhart/table.htm.  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 978-0-443-06911-6. 
  4. ↑ 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
  5. ↑ "The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease". Pharmacological Reviews 66 (4): 1106–40. October 2014. doi:10.1124/pr.113.007781. PMID 25244930. 
  6. ↑ "The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling". Prostaglandins & Other Lipid Mediators 113-115: 2–12. October 2014. doi:10.1016/j.prostaglandins.2014.09.001. PMID 25240260. 
  7. ↑ "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. March 2014. doi:10.1194/jlr.M047357. PMID 24634501. 
  8. ↑ "Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1851 (4): 356–65. April 2015. doi:10.1016/j.bbalip.2014.07.020. PMID 25093613. 
  9. ↑ "Human cytochrome P450 epoxygenases: variability in expression and role in inflammation-related disorders". Pharmacology & Therapeutics 144 (2): 134–61. November 2014. doi:10.1016/j.pharmthera.2014.05.011. PMID 24882266. 

External links

Further reading



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