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Gene Review

CYP2T1P  -  cytochrome P450, family 2, subfamily T,...

Homo sapiens

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Disease relevance of CYP2T2P

  • Therefore, the authors investigated the protein expression of Glutathione S-transferase (GST) isoforms and cytochrome P450 (CYP) known to be involved in the metabolism of steroid hormones and endogenous as well as exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression [1].
  • All six human CYP promoters are active in driving reporter gene expression in cultured hepatic HepG2 cells and non-hepatic cells such as human embryonic kidney fibroblasts (293 cells) and murine melanoma cells (BL-16) as well as cells in intact mouse liver, lung, heart, kidney and spleen [2].
  • The activity of cytochrome P450 (CYP) 3A4, the most important enzyme in human drug metabolism, is decreased in uremia [3].
  • With this information, a link between CYP expression and activity and CVD, such as hypertension, coronary artery disease (CAD), myocardial infarction, heart failure, stroke, and cardiomyopathy and arrhythmias, has been established [4].
  • In the HepG2 human liver cancer cell line, sulindac caused a sustained, dose-dependent increase in CYP enzyme activity [5].

Psychiatry related information on CYP2T2P


High impact information on CYP2T2P

  • The role of these enzymes in toxicological response is exemplified by an autosomal recessive polymorphism at the cytochrome P450 CYP2D6 debrisoquine hydroxylase locus which results in the severely compromised metabolism of at least 25 drugs, and which in some cases can lead to life-threatening side-effects [10].
  • This product resulted from targeted disruption of the gene, designated eryF (systematic nomenclature, CYP107), that apparently codes for the cytochrome P450, 6-deoxyerythronolide B (DEB) hydroxylase, which converts DEB to erythronolide B (EB) [11].
  • The regulation of cytochrome P-450 gene expression [12].
  • The rationale for implicating metabolites of thiono-sulfur compounds other than atomic sulfur in these effects derives from the experiments with thioacetamide and the fact that atomic sulfur is highly reactive and appears to bind predominantly or exclusively to cytochrome P-450 [13].
  • Functional and biochemical data have suggested a role for the cytochrome P450 arachidonate monooxygenases in the pathophysiology of hypertension, a leading cause of cardiovascular, cerebral, and renal morbidity and mortality [14].

Chemical compound and disease context of CYP2T2P


Biological context of CYP2T2P

  • The koala CYP4A15 cDNA-expressed enzyme catalysed lauric acid hydroxylation at the rates of 0.45+/-0.18 nmol/min/mg protein and 4.79+/-1.91 nmol/min/nmol CYP (mean+/-SD, n=3), which were comparable to that of rat CYP4A subfamilies [20].
  • The human cytochrome P450 (P450) system is implicated in many drug interactions [21].
  • The current study investigated a novel approach in assessing cytochrome P450 (P450) enzyme induction in an immortalized cell line using a cocktail of five P450 substrate probes compared with the traditional single-probe approach [22].
  • Genetic variation of human cytochrome p450 reductase as a potential biomarker for mitomycin C-induced cytotoxicity [23].
  • A functional linkage between potent induction of the major CYP (1-3) genes and transcriptional down-regulation of MDR1 gene in drug-resistant tumor cells is hereby hypothesized [24].

Anatomical context of CYP2T2P

  • Using CYP supersomes and liver microsomes, it was shown that aplidine was metabolised mainly by CYP3A4 and also by CYP2A6, 2E1 and 4A11 [25].
  • In accordance with the findings in microsomes and CYP supersomes, a significant effect of specific CYP2A6, 2E1, 3A4 and 4A11 inhibitors on the cytotoxicity of aplidine in Hep G2 and IGROV-1 cells could be observed [25].
  • Total CYP content for koala CYP4A15-expressed protein in Cos-7 cells was 0.094+/-0.001 nmol/mg protein (mean+/-SD, n=3) with negligible CYP content in untransfected Cos-7 cells lysate [20].
  • Utility of long-term cultured human hepatocytes as an in vitro model for cytochrome p450 induction [26].
  • Induction of Cytochrome P450: Assessment in an Immortalized Human Hepatocyte Cell Line (Fa2N4) Using a Novel Higher Throughput Cocktail Assay [22].

Associations of CYP2T2P with chemical compounds

  • These studies verify the capacity of human skin to metabolize RA, although substantial differences exist in CYP expression between normal skin and 3D skin models compared to monolayer cultures [27].
  • Effects of repeated green tea catechin administration on human cytochrome p450 activity [28].
  • Cytochrome p450 and glutathione s-transferase mRNA expression in human fetal liver hematopoietic stem cells [29].
  • Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation [30].
  • Cytochrome P450 (CYP) omega-oxidases convert arachidonic acid (AA) to 20-hydroxyeicosatetraenoic acid (20-HETE), a lipid mediator that modulates vascular tone [31].

Enzymatic interactions of CYP2T2P

  • NAD(P)H:quinone oxidoreductase (NQO1) is a flavoprotein which catalyzes the two-electron reduction of quinones and azo-dyes and thus prevents the formation of free radicals and toxic oxygen metabolites that may be generated by the one-electron reductions catalyzed by cytochrome P450 reductase [32].
  • A common oxidase (cytochrome P-450) appears to catalyze both NADH- and NADPH-supported aromatization [33].

Regulatory relationships of CYP2T2P


Other interactions of CYP2T2P


Analytical, diagnostic and therapeutic context of CYP2T2P

  • The structural and functional aspects of cytochrome P450 (CYP) enzymes are reviewed in the light of current developments in X-ray crystallography and other physical evidence, together with recent findings on the regulation of, and polymorphisms in, the human drug-metabolizing CYPs [41].
  • Cytochrome P450 (P450) induction may have considerable implications for drug therapy [26].
  • We investigated the ability of CYP enzymes in rat, rabbit and human hepatic microsomes to oxidize ellipticine and evaluated suitable animal models mimicking its oxidation in humans [42].
  • CYP promoter sequences were amplified by PCR using human liver genomic DNA as the template and cloned into pGL3-Basic vectors that contain a luciferase reporter gene but lack promoter or enhancer sequences [2].
  • Using HPLC and GC/MS, four cytochrome P450-arachidonic acid metabolites were tentatively but not unequivocally identified as epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acid (DHT) and 19- and 20-hydroxyeicosatetraenoic acids, suggesting the involvement of two major cytochrome P450 enzymes, epoxygenase and omega/omega-1 hydroxylases [43].


  1. Expression of xenobiotic and steroid hormone metabolizing enzymes in human breast carcinomas. Haas, S., Pierl, C., Harth, V., Pesch, B., Rabstein, S., Brüning, T., Ko, Y., Hamann, U., Justenhoven, C., Brauch, H., Fischer, H.P. Int. J. Cancer (2006) [Pubmed]
  2. Direct assessment of promoter activity of human cytochrome p450 genes using optimized transfection in vitro and in vivo. Al-Dosari, M., Zhang, G., Knapp, J.E., Liu, D. Biosci. Rep. (2006) [Pubmed]
  3. Hemodialysis acutely improves hepatic CYP3A4 metabolic activity. Nolin, T.D., Appiah, K., Kendrick, S.A., Le, P., McMonagle, E., Himmelfarb, J. J. Am. Soc. Nephrol. (2006) [Pubmed]
  4. Cytochrome P450 enzymes: Central players in cardiovascular health and disease. Elbekai, R.H., El-Kadi, A.O. Pharmacol. Ther. (2006) [Pubmed]
  5. Sulindac regulates the aryl hydrocarbon receptor-mediated expression of Phase 1 metabolic enzymes in vivo and in vitro. Ciolino, H.P., MacDonald, C.J., Memon, O.S., Bass, S.E., Yeh, G.C. Carcinogenesis (2006) [Pubmed]
  6. Potential interactions of methylphenidate and atomoxetine with dextromethorphan. Ciccone, P.E., Ramabadran, K., Jessen, L.M. Journal of the American Pharmacists Association : JAPhA. (2006) [Pubmed]
  7. Long lasting effects of prenatal exposure to deltamethrin on cerebral and hepatic cytochrome P450s and behavioral activity in rat offspring. Johri, A., Yadav, S., Singh, R.L., Dhawan, A., Ali, M., Parmar, D. Eur. J. Pharmacol. (2006) [Pubmed]
  8. Metabolic basis of ethanol-induced cytotoxicity in recombinant HepG2 cells: Role of nonoxidative metabolism. Wu, H., Cai, P., Clemens, D.L., Jerrells, T.R., Ansari, G.A., Kaphalia, B.S. Toxicol. Appl. Pharmacol. (2006) [Pubmed]
  9. Tissue specificity of induction of hamster monooxygenase activity by ethanol. Ueng, T.H., Ju, J.M., Tsai, J.N. Proc. Natl. Sci. Counc. Repub. China B (1989) [Pubmed]
  10. Identification of the primary gene defect at the cytochrome P450 CYP2D locus. Gough, A.C., Miles, J.S., Spurr, N.K., Moss, J.E., Gaedigk, A., Eichelbaum, M., Wolf, C.R. Nature (1990) [Pubmed]
  11. An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea. Weber, J.M., Leung, J.O., Swanson, S.J., Idler, K.B., McAlpine, J.B. Science (1991) [Pubmed]
  12. The regulation of cytochrome P-450 gene expression. Whitlock, J.P. Annu. Rev. Pharmacol. Toxicol. (1986) [Pubmed]
  13. Toxicology of thiono-sulfur compounds. Neal, R.A., Halpert, J. Annu. Rev. Pharmacol. Toxicol. (1982) [Pubmed]
  14. Salt-sensitive hypertension is associated with dysfunctional Cyp4a10 gene and kidney epithelial sodium channel. Nakagawa, K., Holla, V.R., Wei, Y., Wang, W.H., Gatica, A., Wei, S., Mei, S., Miller, C.M., Cha, D.R., Price, E., Zent, R., Pozzi, A., Breyer, M.D., Guan, Y., Falck, J.R., Waterman, M.R., Capdevila, J.H. J. Clin. Invest. (2006) [Pubmed]
  15. Renal pathophysiology after systemic administration of recombinant adenovirus: changes in renal cytochromes P450 based on vector dose. Le, H.T., Boquet, M.P., Clark, E.A., Callahan, S.M., Croyle, M.A. Hum. Gene Ther. (2006) [Pubmed]
  16. Population Pharmacokinetics of the BEACOPP Polychemotherapy Regimen in Hodgkin's Lymphoma and its Effect on Myelotoxicity. Wilde, S., Jetter, A., Rietbrock, S., Kasel, D., Engert, A., Josting, A., Klimm, B., Hempel, G., Reif, S., Jaehde, U., Merkel, U., Busse, D., Schwab, M., Diehl, V., Fuhr, U. Clinical pharmacokinetics (2007) [Pubmed]
  17. Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/reperfusion injury. Seubert, J.M., Zeldin, D.C., Nithipatikom, K., Gross, G.J. Prostaglandins Other Lipid Mediat. (2007) [Pubmed]
  18. The Potential for Clinically Significant Drug-Drug Interactions Involving the CYP 2D6 System: Effects with Fluoxetine and Paroxetine versus Sertraline. Preskorn, S.H., Shah, R., Neff, M., Golbeck, A.L., Choi, J. Journal of psychiatric practice (2007) [Pubmed]
  19. Hydroxylation of Oleanolic Acid to Queretaroic Acid by Cytochrome P450 from Nonomuraea recticatena. Fujii, Y., Hirosue, S., Fujii, T., Matsumoto, N., Agematu, H., Arisawa, A. Biosci. Biotechnol. Biochem. (2006) [Pubmed]
  20. Cloning and expression of koala (Phascolarctos cinereus) liver cytochrome P450 CYP4A15. Ngo, S.N., McKinnon, R.A., Stupans, I. Gene (2006) [Pubmed]
  21. An evaluation of the cytochrome p450 inhibition potential of lisdexamfetamine in human liver microsomes. Krishnan, S., Moncrief, S. Drug Metab. Dispos. (2007) [Pubmed]
  22. Induction of Cytochrome P450: Assessment in an Immortalized Human Hepatocyte Cell Line (Fa2N4) Using a Novel Higher Throughput Cocktail Assay. Youdim, K.A., Tyman, C.A., Jones, B.C., Hyland, R. Drug Metab. Dispos. (2007) [Pubmed]
  23. Genetic variation of human cytochrome p450 reductase as a potential biomarker for mitomycin C-induced cytotoxicity. Wang, S.L., Han, J.F., He, X.Y., Wang, X.R., Hong, J.Y. Drug Metab. Dispos. (2007) [Pubmed]
  24. Significant transcriptional down-regulation of the human MDR1 gene by beta-naphthoflavone: A proposed hypothesis linking potent CYP gene induction to MDR1 inhibition. Nwankwo, J.O. Med. Hypotheses (2007) [Pubmed]
  25. In vitro characterization of the human biotransformation pathways of aplidine, a novel marine anti-cancer drug. Brandon, E.F., Sparidans, R.W., van Ooijen, R.D., Meijerman, I., Lazaro, L.L., Manzanares, I., Beijnen, J.H., Schellens, J.H. Investigational new drugs (2007) [Pubmed]
  26. Utility of long-term cultured human hepatocytes as an in vitro model for cytochrome p450 induction. Meneses-Lorente, G., Pattison, C., Guyomard, C., Chesné, C., Heavens, R., Watt, A.P., Sohal, B. Drug Metab. Dispos. (2007) [Pubmed]
  27. Skin Retinoid Concentrations Are Modulated by CYP26AI Expression Restricted to Basal Keratinocytes in Normal Human Skin and Differentiated 3D Skin Models. Heise, R., Mey, J., Neis, M.M., Marquardt, Y., Joussen, S., Ott, H., Wiederholt, T., Kurschat, P., Megahed, M., Bickers, D.R., Merk, H.F., Baron, J.M. J. Invest. Dermatol. (2006) [Pubmed]
  28. Effects of repeated green tea catechin administration on human cytochrome p450 activity. Chow, H.H., Hakim, I.A., Vining, D.R., Crowell, J.A., Cordova, C.A., Chew, W.M., Xu, M.J., Hsu, C.H., Ranger-Moore, J., Alberts, D.S. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  29. Cytochrome p450 and glutathione s-transferase mRNA expression in human fetal liver hematopoietic stem cells. Shao, J., Stapleton, P.L., Lin, Y.S., Gallagher, E.P. Drug Metab. Dispos. (2007) [Pubmed]
  30. Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Akutsu, T., Kobayashi, K., Sakurada, K., Ikegaya, H., Furihata, T., Chiba, K. Drug Metab. Dispos. (2007) [Pubmed]
  31. Oxygenation of omega-3 fatty acids by human cytochrome P450 4F3B: Effect on 20-hydroxyeicosatetraenoic acid production. Harmon, S.D., Fang, X., Kaduce, T.L., Hu, S., Raj Gopal, V., Falck, J.R., Spector, A.A. Prostaglandins Leukot. Essent. Fatty Acids (2006) [Pubmed]
  32. High levels of expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene in tumor cells compared to normal cells of the same origin. Cresteil, T., Jaiswal, A.K. Biochem. Pharmacol. (1991) [Pubmed]
  33. The roles of NADH in the support of steroid aromatization by human placental microsomes. Sheean, L.A., Meigs, R.A. Steroids (1983) [Pubmed]
  34. Tumor necrosis factor as a potent inhibitor of adrenocorticotropin-induced cortisol production and steroidogenic P450 enzyme gene expression in cultured human fetal adrenal cells. Jäättelä, M., Ilvesmäki, V., Voutilainen, R., Stenman, U.H., Saksela, E. Endocrinology (1991) [Pubmed]
  35. Interaction of H2-receptor antagonists and benzodiazepine sedation. A double-blind placebo-controlled investigation of the effects of cimetidine and ranitidine on recovery after intravenous midazolam. Sanders, L.D., Whitehead, C., Gildersleve, C.D., Rosen, M., Robinson, J.O. Anaesthesia. (1993) [Pubmed]
  36. Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. Studies in rats and patients. Watkins, P.B., Murray, S.A., Winkelman, L.G., Heuman, D.M., Wrighton, S.A., Guzelian, P.S. J. Clin. Invest. (1989) [Pubmed]
  37. Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2. Pascoe, L., Curnow, K.M., Slutsker, L., Connell, J.M., Speiser, P.W., New, M.I., White, P.C. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  38. Human liver microsomal cytochrome P-450 mephenytoin 4-hydroxylase, a prototype of genetic polymorphism in oxidative drug metabolism. Purification and characterization of two similar forms involved in the reaction. Shimada, T., Misono, K.S., Guengerich, F.P. J. Biol. Chem. (1986) [Pubmed]
  39. An evaluation of cytochrome P450 isoform activities in the female dark agouti (DA) rat: relevance to its use as a model of the CYP2D6 poor metaboliser phenotype. Barham, H.M., Lennard, M.S., Tucker, G.T. Biochem. Pharmacol. (1994) [Pubmed]
  40. Linkage relationships of the apolipoprotein C1 gene and a cytochrome P450 gene (CYP2A) to myotonic dystrophy. Walsh, K.V., Harley, H.G., Brook, J.D., Rundle, S.A., Sarfarazi, M., Harper, P.S., Shaw, D.J. Hum. Genet. (1990) [Pubmed]
  41. Structural modelling of the human drug-metabolizing cytochromes p450. Lewis, D.F., Ito, Y., Goldfarb, P.S. Current medicinal chemistry. (2006) [Pubmed]
  42. Oxidation pattern of the anticancer drug ellipticine by hepatic microsomes - similarity between human and rat systems. Stiborov??, M., Borek-Dohalsk??, L., Aimov??, D., Kotrbov??, V., Kukackov??, K., Janouchov??, K., Rupertov??, M., Ryslav??, H., Hudecek, J., Frei, E. Gen. Physiol. Biophys. (2006) [Pubmed]
  43. Cytochrome P450-dependent arachidonic acid metabolism in human kidney. Schwartzman, M.L., Martasek, P., Rios, A.R., Levere, R.D., Solangi, K., Goodman, A.I., Abraham, N.G. Kidney Int. (1990) [Pubmed]
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