cytochrome p 450 enzyme system


Summary: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.

Top Publications

  1. Ramsey J, Rider D, Walsh T, De Vos M, Gordon K, Ponnala L, et al. Comparative analysis of detoxification enzymes in Acyrthosiphon pisum and Myzus persicae. Insect Mol Biol. 2010;19 Suppl 2:155-64 pubmed publisher
    ..However, given the incomplete M. persicae cDNA data set, the number of identified detoxification genes in this species is likely to be an underestimate...
  2. Nicolo C, Flück C, Mullis P, Pandey A. Restoration of mutant cytochrome P450 reductase activity by external flavin. Mol Cell Endocrinol. 2010;321:245-52 pubmed publisher
    ..Using FMN supplemented assays we have demonstrated restoration of the defective POR activity in vitro. ..
  3. Schlangen K, Miosic S, Halbwirth H. Allelic variants from Dahlia variabilis encode flavonoid 3'-hydroxylases with functional differences in chalcone 3-hydroxylase activity. Arch Biochem Biophys. 2010;494:40-5 pubmed publisher
    ..This is the first identification of an F3'H which is able to catalyze chalcone 3-hydroxylation to a physiologically relevant extent from any plant species. ..
  4. Paquette S, Jensen K, Bak S. A web-based resource for the Arabidopsis P450, cytochromes b5, NADPH-cytochrome P450 reductases, and family 1 glycosyltransferases ( Phytochemistry. 2009;70:1940-7 pubmed publisher is a sequence repository of manually curated sequences, multiple sequence alignments, phylogenetic trees, sequence motif logos, 3D structures, intron-exon maps, and customized BLAST datasets. ..
  5. Nelson D. The cytochrome p450 homepage. Hum Genomics. 2009;4:59-65 pubmed
    ..The organisation and content of the Homepage are described...
  6. Wang C, Yen J, Cheng Y, Lin C, Hsieh C, Gau R, et al. Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet-induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles. Food Nutr Res. 2017;61:1379861 pubmed publisher
  7. Sárközy M, Szűcs G, Pipicz M, Zvara Ã, Éder K, Fekete V, et al. The effect of a preparation of minerals, vitamins and trace elements on the cardiac gene expression pattern in male diabetic rats. Cardiovasc Diabetol. 2015;14:85 pubmed publisher
    ..Our results and further studies exploring the mechanistic role of individual genes may contribute to the prevention or diagnosis of cardiac complications in diabetes. ..
  8. Mazzio E, Soliman K. Whole-transcriptomic Profile of SK-MEL-3 Melanoma Cells Treated with the Histone Deacetylase Inhibitor: Trichostatin A. Cancer Genomics Proteomics. 2018;15:349-364 pubmed publisher
    ..TSA does not alter HDAC transcripts nor BRAF itself, but down-regulates critical components of the MAPK/MEK/BRAF oncogenic pathway, initiating a mitotic arrest. ..
  9. Zhao Z, Barcus M, Kim J, Lum K, Mills C, Lei X. High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs. J Nutr. 2016;146:1625-33 pubmed publisher
    ..Our research showed novel roles, to our best knowledge, and mechanisms of high selenium intakes in regulating the metabolism of protein, along with that of lipid, in a tissue-specific fashion in pigs. ..

More Information


  1. Zhong W, Qian K, Xiong J, Ma K, Wang A, Zou Y. Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-?B related signaling. Biomed Pharmacother. 2016;83:302-313 pubmed publisher
    ..Strategies to inhibit inflammation and apoptosis signaling may provide alternatives to the current clinical approaches to improve oxidative responses of endotoxemia. ..
  2. Ansari R, Husain K, Rizvi S. Role of Transcription Factors in Steatohepatitis and Hypertension after Ethanol: The Epicenter of Metabolism. Biomolecules. 2016;6: pubmed publisher
    ..In addition to these transcription factors, activator protein-1 may also be activated in hepatocytes due to its association with resolution of increased ROS. These transcription factors are central to alcohol-mediated hepatotoxicity. ..
  3. Xiong Y, Chen H, Lin P, Wang A, Wang L, Jin Y. ATF6 knockdown decreases apoptosis, arrests the S phase of the cell cycle, and increases steroid hormone production in mouse granulosa cells. Am J Physiol Cell Physiol. 2017;312:C341-C353 pubmed publisher
    ..The present study extends our understanding and provides new insights into the physiological significance of ATF6, a key signal transducer of ER stress, in ovarian granulosa cells. ..
  4. Liao W, Qi Y, Wang L, Dong X, Xu T, Ding C, et al. Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice. World J Gastroenterol. 2015;21:10375-84 pubmed publisher
    ..Recql5 protects the liver against LPS/D-Gal-induced injury through suppression of hepatocyte apoptosis and oxidative stress and modulation of CYP450 expression. ..
  5. Hassan M, Ghobara M. Antifibrotic effect of meloxicam in rat liver: role of nuclear factor kappa B, proinflammatory cytokines, and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol. 2016;389:971-83 pubmed publisher
    ..Abrogation of oxidative stress and modulation of liver-metabolizing enzymes (CYP2E1 and GST) were also involved. ..
  6. Echizen H. The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations. Clin Pharmacokinet. 2016;55:409-18 pubmed publisher
    ..Neither severe liver toxicity nor neuroendocrine tumor has been reported in patients receiving vonoprazan. ..
  7. Cao X, Du J, Zhang Y, Yan J, Hu X. Hyperlipidemia exacerbates cerebral injury through oxidative stress, inflammation and neuronal apoptosis in MCAO/reperfusion rats. Exp Brain Res. 2015;233:2753-65 pubmed publisher
  8. Subramaniam E, Colazo M, Gobikrushanth M, Sun Y, Ruiz Sanchez A, Ponce Barajas P, et al. Effects of reducing dietary starch content by replacing barley grain with wheat dried distillers grains plus solubles in dairy cow rations on ovarian function. J Dairy Sci. 2016;99:2762-2774 pubmed publisher
  9. Ryu B, Kim C, Oh H, Kim U, Kim J, Jung C, et al. Development of an alternative zebrafish model for drug-induced intestinal toxicity. J Appl Toxicol. 2017;: pubmed publisher
    ..These results suggest that zebrafish model is sufficiently worth developing as an intestinal toxicity model that can replace or compensate the rat model or Caco-2 cell model...
  10. Abraham N, Sodhi K, Silvis A, Vanella L, Favero G, Rezzani R, et al. CYP2J2 targeting to endothelial cells attenuates adiposity and vascular dysfunction in mice fed a high-fat diet by reprogramming adipocyte phenotype. Hypertension. 2014;64:1352-61 pubmed publisher
  11. Kanbur M, Siliğ Y, Eraslan G, Karabacak M, Soyer Sarıca Z, Şahin S. The toxic effect of cypermethrin, amitraz and combinations of cypermethrin-amitraz in rats. Environ Sci Pollut Res Int. 2016;23:5232-42 pubmed publisher
  12. Lee J, Kang M, Wang H, Naik G, Mobley J, Sonpavde G, et al. Endostatin inhibits androgen-independent prostate cancer growth by suppressing nuclear receptor-mediated oxidative stress. FASEB J. 2017;31:1608-1619 pubmed publisher
    ..Kang, M., Wang, H., Naik, G., Mobley, J. A., Sonpavde, G., Garvey, W. T., Darley-Usmar, V. M., Ponnazhagan, S. Endostatin inhibits androgen-independent prostate cancer growth by suppressing nuclear receptor-mediated oxidative stress. ..
  13. Kojima Yuasa A, Goto M, Yoshikawa E, Morita Y, Sekiguchi H, Sutoh K, et al. Protective Effects of Hydrolyzed Nucleoproteins from Salmon Milt against Ethanol-Induced Liver Injury in Rats. Mar Drugs. 2016;14: pubmed publisher
    ..These results suggest that DNSM treatment represents a novel tool for the prevention of alcohol-induced liver injury. ..
  14. Song B, Akbar M, Jo I, Hardwick J, Abdelmegeed M. Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease. Adv Pharmacol. 2015;74:303-72 pubmed publisher
    ..We also discuss translational research opportunities with natural and/or synthetic antioxidants, which can prevent or delay the onset of inflammation and liver disease. ..
  15. Pan Y, Long X, Yi R, Zhao X. Polyphenols in Liubao Tea Can Prevent CCl?-Induced Hepatic Damage in Mice through Its Antioxidant Capacities. Nutrients. 2018;10: pubmed publisher
    ..Thus, PLT imparts preventive effects against CCl?-induced liver injury, which is similar to silymarin. ..
  16. Li L, Zhou Y, Li Y, Wang L, Arai H, Xu Y. In vitro and in vivo antioxidative and hepatoprotective activity of aqueous extract of Cortex Dictamni. World J Gastroenterol. 2017;23:2912-2927 pubmed publisher
    ..The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation. ..
  17. Zhou Y, Zhou Z, Batistel F, Martínez Cortés I, Pate R, Luchini D, et al. Methionine and choline supply alter transmethylation, transsulfuration, and cytidine 5'-diphosphocholine pathways to different extents in isolated primary liver cells from dairy cows. J Dairy Sci. 2018;101:11384-11395 pubmed publisher
    ..The relevance of these data in vivo merit further study. ..
  18. Sadeeshkumar V, Duraikannu A, Ravichandran S, Fredrick W, Sivaperumal R, Kodisundaram P. Protective effects of dieckol on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Biomed Pharmacother. 2016;84:1810-1819 pubmed publisher
  19. He H, Mennone A, Boyer J, Cai S. Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct-ligated rats and human hepatic cells. Hepatology. 2011;53:548-57 pubmed publisher
    ..Our findings indicate that the addition of RA to UDCA reduces the bile salt pool size and liver fibrosis and might be an effective supplemental therapy with UDCA for cholestatic diseases. ..
  20. Ip B, Liu C, Lichtenstein A, von Lintig J, Wang X. Lycopene and apo-10'-lycopenoic acid have differential mechanisms of protection against hepatic steatosis in β-carotene-9',10'-oxygenase knockout male mice. J Nutr. 2015;145:268-76 pubmed publisher
    ..Sex disparity of BCO2-KO mice was observed in the outcomes of HSFD-induced liver steatosis and plasma lipids. ..
  21. Hammond E, Stewart B, Peek J, Shelling A, Cree L. Assessing embryo quality by combining non-invasive markers: early time-lapse parameters reflect gene expression in associated cumulus cells. Hum Reprod. 2015;30:1850-60 pubmed publisher
    ..J.C.P. has a 0.5% shareholding in Fertility Associates. All other authors of this manuscript have nothing to declare and no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. ..
  22. Hoopes S, Gruzdev A, Edin M, Graves J, Bradbury J, Flake G, et al. Generation and characterization of epoxide hydrolase 3 (EPHX3)-deficient mice. PLoS ONE. 2017;12:e0175348 pubmed publisher
    ..We conclude that genetic disruption of Ephx3 does not result in an overt phenotype and has no significant effects on the metabolism of EETs or EpOMEs in vivo. ..
  23. Yamaza T, Alatas F, Yuniartha R, Yamaza H, Fujiyoshi J, Yanagi Y, et al. In vivo hepatogenic capacity and therapeutic potential of stem cells from human exfoliated deciduous teeth in liver fibrosis in mice. Stem Cell Res Ther. 2015;6:171 pubmed publisher
    ..This study indicates that transplanted SHED improve hepatic dysfunction and directly transform into hepatocytes without cell fusion in CCl4-treated mice, suggesting that SHED may provide a feasible cell source for liver regeneration. ..