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Gene Review

CYP2C19  -  cytochrome P450, family 2, subfamily C,...

Homo sapiens

Synonyms: (R)-limonene 6-monooxygenase, (S)-limonene 6-monooxygenase, (S)-limonene 7-monooxygenase, CPCJ, CYP2C, ...
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Disease relevance of CYP2C19


High impact information on CYP2C19


Chemical compound and disease context of CYP2C19


Biological context of CYP2C19


Anatomical context of CYP2C19


Associations of CYP2C19 with chemical compounds

  • Induction is most pronounced in slow metabolizers of S-mephenytoin because CYP2C19 (S-mephenytoin hydroxylase) is responsible for the elimination of omeprazole [20].
  • Moreover, the S/R ratio of mephenytoin showed a small but significant increase (median difference, 0.02; 95% CI, 0 to 0.31; versus 0; 95% CI, -0.01 to 0.06), indicating an inhibition of CYP2C19 [21].
  • Ticlopidine inhibition of phenytoin metabolism mediated by potent inhibition of CYP2C19 [1].
  • RESULTS: When given alone, the apparent oral clearance of voriconazole after single oral dosing was 26%+/-16% (P > .05) lower in CYP2C19*1/*2 individuals and 66%+/-14% (P < .01) lower in CYP2C19 PMs [13].
  • The disappearance of MPA did not correlate with either the activity metabolized via CYP2C9 (diclofenac 4'-hydroxylase activity) or the activity metabolized via CYP2C19 (S-mephenytoin 4'-hydroxylase activity) [22].
  • Neither CYP2C19 nor CYP3A4 could 21-hydroxylate 17OHP [23].

Physical interactions of CYP2C19


Regulatory relationships of CYP2C19

  • CYP2C9 and CYP2C19 provided enhanced formation of R-EDDP and CYP2D6 incubation resulted in the preferential conversion to S-EDDP [26].
  • NaPB significantly induced levels of CYP3A4 apoprotein to 255% of control and RIF significantly induced levels of CYP2C19 and CYP3A4 apoproteins to 265 and 330% of control, respectively [27].
  • Catalytic activities of CYP2C9 and CYP2C19 were enhanced by addition of b5 in reconstituted systems but not in the P450/NPR membranes [28].
  • Expression with hCAR also up-regulated endogenous CYP2C19 mRNA content in HepG2 cells [25].
  • Cotransfection with hCAR, mCAR, or hPXR in HepG2 cells up-regulated transcription of CYP2C19 promoter constructs, whereas mutation of the -1891-bp CAR-RE abolished up-regulation [25].

Other interactions of CYP2C19

  • CYP2C19 may have a role in bladder cancer risk, but polymorphisms in CYP1A1 and 2E1 had no statistically significant impact [29].
  • Determination of metabolic genotype revealed that the patient had a wild-type genotype for CYP2C9, CYP2C19, and CYP2D6 [1].
  • Although the induction of CYP1A2 may be of some clinical relevance, the small inhibition of CYP2C19 is probably unimportant [21].
  • Of the participants, 49% were white, 31% were black, and 19% were Hispanic. Plasma exposure to efavirenz and nelfinavir in each population was significantly associated with the polymorphisms CYP2B6 516G-->T and CYP2C19 681G-->A, respectively [30].
  • The cDNA expressed enzymes CYP2C8, CYP2C9 and CYP2C19 catalyzed varying rates of lansoprazole 5-hydroxylation at a substrate concentration of 50 microM, but only CYPC19 catalyzed this reaction at 1 microM [31].

Analytical, diagnostic and therapeutic context of CYP2C19


  1. Ticlopidine inhibition of phenytoin metabolism mediated by potent inhibition of CYP2C19. Donahue, S.R., Flockhart, D.A., Abernethy, D.R., Ko, J.W. Clin. Pharmacol. Ther. (1997) [Pubmed]
  2. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Desta, Z., Zhao, X., Shin, J.G., Flockhart, D.A. Clinical pharmacokinetics. (2002) [Pubmed]
  3. Engineering human cytochrome P450 enzymes into catalytically self-sufficient chimeras using molecular Lego. Dodhia, V.R., Fantuzzi, A., Gilardi, G. J. Biol. Inorg. Chem. (2006) [Pubmed]
  4. Role of polymorphic human cytochrome P450 enzymes in estrone oxidation. Cribb, A.E., Knight, M.J., Dryer, D., Guernsey, J., Hender, K., Tesch, M., Saleh, T.M. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  5. Cytochrome P450 2C is an EDHF synthase in coronary arteries. Fisslthaler, B., Popp, R., Kiss, L., Potente, M., Harder, D.R., Fleming, I., Busse, R. Nature (1999) [Pubmed]
  6. Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Gardiner, S.J., Begg, E.J. Pharmacol. Rev. (2006) [Pubmed]
  7. Effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism. Sagar, M., Tybring, G., Dahl, M.L., Bertilsson, L., Seensalu, R. Gastroenterology (2000) [Pubmed]
  8. Conversion of the HIV protease inhibitor nelfinavir to a bioactive metabolite by human liver CYP2C19. Hirani, V.N., Raucy, J.L., Lasker, J.M. Drug Metab. Dispos. (2004) [Pubmed]
  9. CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson's disease, as revealed from experiments with recombinant enzymes. Hidestrand, M., Oscarson, M., Salonen, J.S., Nyman, L., Pelkonen, O., Turpeinen, M., Ingelman-Sundberg, M. Drug Metab. Dispos. (2001) [Pubmed]
  10. Clinical importance of non-genetic and genetic cytochrome P450 function tests in liver disease. Tanaka, E. Journal of clinical pharmacy and therapeutics. (1998) [Pubmed]
  11. Esomeprazole-induced healing of gastroesophageal reflux disease is unrelated to the genotype of CYP2C19: evidence from clinical and pharmacokinetic data. Schwab, M., Klotz, U., Hofmann, U., Schaeffeler, E., Leodolter, A., Malfertheiner, P., Treiber, G. Clin. Pharmacol. Ther. (2005) [Pubmed]
  12. RNA molecules containing exons originating from different members of the cytochrome P450 2C gene subfamily (CYP2C) in human epidermis and liver. Zaphiropoulos, P.G. Nucleic Acids Res. (1999) [Pubmed]
  13. Potent cytochrome P450 2C19 genotype-related interaction between voriconazole and the cytochrome P450 3A4 inhibitor ritonavir. Mikus, G., Schöwel, V., Drzewinska, M., Rengelshausen, J., Ding, R., Riedel, K.D., Burhenne, J., Weiss, J., Thomsen, T., Haefeli, W.E. Clin. Pharmacol. Ther. (2006) [Pubmed]
  14. Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Odani, A., Hashimoto, Y., Otsuki, Y., Uwai, Y., Hattori, H., Furusho, K., Inui, K. Clin. Pharmacol. Ther. (1997) [Pubmed]
  15. Thalidomide metabolism by the CYP2C subfamily. Ando, Y., Fuse, E., Figg, W.D. Clin. Cancer Res. (2002) [Pubmed]
  16. The role of CYP2C in the in vitro bioactivation of the contraceptive steroid desogestrel. Gentile, D.M., Verhoeven, C.H., Shimada, T., Back, D.J. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  17. Evaluation of time-dependent cytochrome P450 inhibition using cultured human hepatocytes. McGinnity, D.F., Berry, A.J., Kenny, J.R., Grime, K., Riley, R.J. Drug Metab. Dispos. (2006) [Pubmed]
  18. Metabolic characterization of the major human small intestinal cytochrome p450s. Obach, R.S., Zhang, Q.Y., Dunbar, D., Kaminsky, L.S. Drug Metab. Dispos. (2001) [Pubmed]
  19. Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. Klose, T.S., Blaisdell, J.A., Goldstein, J.A. J. Biochem. Mol. Toxicol. (1999) [Pubmed]
  20. The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin. Sarich, T., Kalhorn, T., Magee, S., al-Sayegh, F., Adams, S., Slattery, J., Goldstein, J., Nelson, S., Wright, J. Clin. Pharmacol. Ther. (1997) [Pubmed]
  21. Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men. Jürgens, G., Lange, K.H., Reuther, L.Ø., Rasmussen, B.B., Brøsen, K., Christensen, H.R. Clin. Pharmacol. Ther. (2002) [Pubmed]
  22. Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate. Kobayashi, K., Mimura, N., Fujii, H., Minami, H., Sasaki, Y., Shimada, N., Chiba, K. Clin. Cancer Res. (2000) [Pubmed]
  23. Extraadrenal 21-hydroxylation by CYP2C19 and CYP3A4: effect on 21-hydroxylase deficiency. Gomes, L.G., Huang, N., Agrawal, V., Mendonça, B.B., Bachega, T.A., Miller, W.L. J. Clin. Endocrinol. Metab. (2009) [Pubmed]
  24. Production of inhibitory polyclonal antibodies against cytochrome P450s. Ng, P.S., Imaoka, S., Hiroi, T., Osada, M., Niwa, T., Kamataki, T., Funae, Y. Drug Metab. Pharmacokinet. (2003) [Pubmed]
  25. Identification of constitutive androstane receptor and glucocorticoid receptor binding sites in the CYP2C19 promoter. Chen, Y., Ferguson, S.S., Negishi, M., Goldstein, J.A. Mol. Pharmacol. (2003) [Pubmed]
  26. Capillary electrophoresis to assess drug metabolism induced in vitro using single CYP450 enzymes (Supersomes): application to the chiral metabolism of mephenytoin and methadone. Prost, F., Thormann, W. Electrophoresis (2003) [Pubmed]
  27. Induction of cytochrome P450 enzymes in cultured precision-cut human liver slices. Edwards, R.J., Price, R.J., Watts, P.S., Renwick, A.B., Tredger, J.M., Boobis, A.R., Lake, B.G. Drug Metab. Dispos. (2003) [Pubmed]
  28. Roles of NADPH-P450 reductase and apo- and holo-cytochrome b5 on xenobiotic oxidations catalyzed by 12 recombinant human cytochrome P450s expressed in membranes of Escherichia coli. Yamazaki, H., Nakamura, M., Komatsu, T., Ohyama, K., Hatanaka, N., Asahi, S., Shimada, N., Guengerich, F.P., Shimada, T., Nakajima, M., Yokoi, T. Protein Expr. Purif. (2002) [Pubmed]
  29. Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk. Brockmöller, J., Cascorbi, I., Kerb, R., Roots, I. Cancer Res. (1996) [Pubmed]
  30. Pharmacogenetics of long-term responses to antiretroviral regimens containing Efavirenz and/or Nelfinavir: an Adult Aids Clinical Trials Group Study. Haas, D.W., Smeaton, L.M., Shafer, R.W., Robbins, G.K., Morse, G.D., Labbe, L., Wilkinson, G.R., Clifford, D.B., D'Aquila, R.T., De Gruttola, V., Pollard, R.B., Merigan, T.C., Hirsch, M.S., George, A.L., Donahue, J.P., Kim, R.B. J. Infect. Dis. (2005) [Pubmed]
  31. Identification of the human P450 enzymes involved in lansoprazole metabolism. Pearce, R.E., Rodrigues, A.D., Goldstein, J.A., Parkinson, A. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  32. Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: effects of contents of these two forms in individual human samples. Yamazaki, H., Inoue, K., Shaw, P.M., Checovich, W.J., Guengerich, F.P., Shimada, T. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  33. Comparison of (S)-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Coller, J.K., Somogyi, A.A., Bochner, F. British journal of clinical pharmacology. (1999) [Pubmed]
  34. Influence of azimilide on CYP2C19-mediated metabolism. El Mouelhi, M., Worley, D.J., Kuzmak, B., Destefano, A.J., Thompson, G.A. Journal of clinical pharmacology. (2004) [Pubmed]
  35. Selective and potent inhibition of human CYP2C19 activity by a conformationally targeted antipeptide antibody. Schulz-Utermoehl, T., Mountfield, R.J., Madsen, K., Jørgensen, P.N., Hansen, K.T. Drug Metab. Dispos. (2000) [Pubmed]
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