Experts and Doctors on cytochrome p 450 enzyme system in North Carolina, United States


Locale: North Carolina, United States
Topic: cytochrome p 450 enzyme system

Top Publications

  1. Ibeanu G, Goldstein J, Meyer U, Benhamou S, Bouchardy C, Dayer P, et al. Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther. 1998;286:1490-5 pubmed
    ..Thus, the new CYP2C19*6 allele contributes to the PM phenotype in Caucasians. ..
  2. Tsao C, Wester M, Ghanayem B, Coulter S, Chanas B, Johnson E, et al. Identification of human CYP2C19 residues that confer S-mephenytoin 4'-hydroxylation activity to CYP2C9. Biochemistry. 2001;40:1937-44 pubmed
  3. Jackson J, Ferguson S, Moore R, Negishi M, Goldstein J. The constitutive active/androstane receptor regulates phenytoin induction of Cyp2c29. Mol Pharmacol. 2004;65:1397-404 pubmed
  4. Ibeanu G, Blaisdell J, Ferguson R, Ghanayem B, Brosen K, Benhamou S, et al. A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin. J Pharmacol Exp Ther. 1999;290:635-40 pubmed
    ..Restriction fragment length polymerase chain reaction tests were developed to identify the new allelic variants. ..
  5. Wyde M, Kirwan S, Zhang F, Laughter A, Hoffman H, Bartolucci Page E, et al. Di-n-butyl phthalate activates constitutive androstane receptor and pregnane X receptor and enhances the expression of steroid-metabolizing enzymes in the liver of rat fetuses. Toxicol Sci. 2005;86:281-90 pubmed
    ..Our study shows that DBP is broadly reactive with multiple pathways involved in maintaining steroid and lipid homeostasis. ..
  6. Scollon E, Starr J, Godin S, DeVito M, Hughes M. In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009;37:221-8 pubmed publisher
    ..These species differences and isomer interactions in metabolism of pyrethroids should be considered when assessing the potential adverse health effects of pyrethroid pesticides. ..
  7. de Morais S, Wilkinson G, Blaisdell J, Meyer U, Nakamura K, Goldstein J. Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol. 1994;46:594-8 pubmed
    ..Genetic testing of the families of two Japanese poor metabolizer probands showed that coinheritance of the CYP2C19m1 and CYP2C19m2 alleles was concordant with the autosomal recessive inheritance of the poor metabolizer phenotype. ..
  8. Harris P, Boloor A, Cheung M, Kumar R, Crosby R, Davis Ward R, et al. Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J Med Chem. 2008;51:4632-40 pubmed publisher
  9. Ferguson R, de Morais S, Benhamou S, Bouchardy C, Blaisdell J, Ibeanu G, et al. A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin. J Pharmacol Exp Ther. 1998;284:356-61 pubmed
    ..The two cDNAs were also used in an in vitro coupled transcription/translation assay. CYP2C19 protein was translated only from the CYP2C19*1 allele. These data indicate that CYP2C19*4 represents a new PM allele. ..

More Information


  1. de Morais S, Wilkinson G, Blaisdell J, Nakamura K, Meyer U, Goldstein J. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem. 1994;269:15419-22 pubmed
    ..Finally, the familial inheritance of the deficient allele was found to be concordant with that of the phenotypic trait. ..
  2. Ma J, Ramachandran S, Fiedorek F, Zeldin D. Mapping of the CYP2J cytochrome P450 genes to human chromosome 1 and mouse chromosome 4. Genomics. 1998;49:152-5 pubmed
    ..3-p31.2 by fluorescence in situ hybridization analysis. The proximity of the Cyp2j cluster to the Cyp4a cluster suggests that these genes may be part of a cassette of P450 genes involved in the oxidation of fatty acids. ..
  3. Luo G, Zeldin D, Blaisdell J, Hodgson E, Goldstein J. Cloning and expression of murine CYP2Cs and their ability to metabolize arachidonic acid. Arch Biochem Biophys. 1998;357:45-57 pubmed
    ..CYP2C38 and CYP2C40 were found in liver, brain, kidney, and intestine, with trace amounts in lung and heart, while CYP2C37 and CYP2C39 appeared to be liver specific. ..
  4. Zeldin D, Foley J, Boyle J, Moomaw C, Tomer K, Parker C, et al. Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas. Endocrinology. 1997;138:1338-46 pubmed
  5. London S, Yuan J, Coetzee G, Gao Y, Ross R, Yu M. CYP1A1 I462V genetic polymorphism and lung cancer risk in a cohort of men in Shanghai, China. Cancer Epidemiol Biomarkers Prev. 2000;9:987-91 pubmed
  6. Lewandowski M, Levi P, Hodgson E. Induction of cytochrome P-450 isozymes by mirex and chlordecone. J Biochem Toxicol. 1989;4:195-9 pubmed
    ..The high dose of mirex also induced a small amount of a protein cross reacting with the antibody to IA1. The induction of this isozyme did not, however, contribute significantly to the monooxygenase activities measured. ..
  7. Inoue K, Negishi M. Nuclear receptor CAR requires early growth response 1 to activate the human cytochrome P450 2B6 gene. J Biol Chem. 2008;283:10425-32 pubmed publisher
    ..Thus, synergy of drug activation and the stimulation of cellular signal are necessary for CAR to activate the CYP2B6 gene. ..
  8. King L, Ma J, Srettabunjong S, Graves J, Bradbury J, Li L, et al. Cloning of CYP2J2 gene and identification of functional polymorphisms. Mol Pharmacol. 2002;61:840-52 pubmed
    ..Insofar as CYP2J2 products have effects in the cardiovascular system, we speculate that these variants may be functionally relevant. ..
  9. Wang H, Zhao Y, Bradbury J, Graves J, Foley J, Blaisdell J, et al. Cloning, expression, and characterization of three new mouse cytochrome p450 enzymes and partial characterization of their fatty acid oxidation activities. Mol Pharmacol. 2004;65:1148-58 pubmed
    ..We conclude that these new CYP2C enzymes are probably involved in AA and linoleic acid metabolism in mouse hepatic and extrahepatic tissues. ..
  10. Wong G, Kawajiri K, Negishi M. Gene family of male-specific testosterone 16 alpha-hydroxylase (C-P-450(16) alpha) in mouse liver: cDNA sequences, neonatal imprinting, and reversible regulation by androgen. Biochemistry. 1987;26:8683-90 pubmed
    ..The putative poly(A) addition signal AATAAA is present for all three clones, but there are polymorphisms in the start sites of polyadenylation.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  11. King L, Gainer J, David G, Dai D, Goldstein J, Brown N, et al. Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension. Pharmacogenet Genomics. 2005;15:7-13 pubmed
    ..Confirmation of these findings in additional populations is warranted. ..
  12. Lindberg R, Negishi M. Alteration of mouse cytochrome P450coh substrate specificity by mutation of a single amino-acid residue. Nature. 1989;339:632-4 pubmed
  13. Dai D, Tang J, Rose R, Hodgson E, Bienstock R, Mohrenweiser H, et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther. 2001;299:825-31 pubmed
    ..The turnover numbers of the CYP3A4 M445T and P467S alleles to metabolize these compounds were not significantly different from those of wild-type CYP3A4. ..
  14. Gasser R, Philpot R. Primary structures of cytochrome P-450 isozyme 5 from rabbit and rat and regulation of species-dependent expression and induction in lung and liver: identification of cytochrome P-450 gene subfamily IVB. Mol Pharmacol. 1989;35:617-25 pubmed
  15. Kliewer S, Moore J, Wade L, Staudinger J, Watson M, Jones S, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998;92:73-82 pubmed
    ..Our results provide evidence for the existence of a novel steroid hormone signaling pathway with potential implications in the regulation of steroid hormone and sterol homeostasis. ..
  16. Ozaki K, Mahler J, Haseman J, Moomaw C, Nicolette M, Nyska A. Unique renal tubule changes induced in rats and mice by the peroxisome proliferators 2,4-dichlorophenoxyacetic acid (2,4-D) and WY-14643. Toxicol Pathol. 2001;29:440-50 pubmed
    ..Although 2,4-D is considered a weak PP for the liver, it was the most effective at inducing renal lesions, indicating that the toxic potency of various PPs will depend on the target organ. ..
  17. Lee S, Perera L, Coulter S, Mohrenweiser H, Jetten A, Goldstein J. The discovery of new coding alleles of human CYP26A1 that are potentially defective in the metabolism of all-trans retinoic acid and their assessment in a recombinant cDNA expression system. Pharmacogenet Genomics. 2007;17:169-80 pubmed
    ..These studies suggest the need for future clinical studies of polymorphisms of CYP26A1 in embryonic development. ..
  18. Ferguson S, LeCluyse E, Negishi M, Goldstein J. Regulation of human CYP2C9 by the constitutive androstane receptor: discovery of a new distal binding site. Mol Pharmacol. 2002;62:737-46 pubmed
  19. Klose T, Blaisdell J, Goldstein J. Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. J Biochem Mol Toxicol. 1999;13:289-95 pubmed
    ..Although CYP2C8 has been shown to be phenobarbital inducible, neither a barbiturate-responsive regulatory sequence (a Barbie box) nor a phenobarbital-responsive enhancer module (PBREM) was found within the upstream region analyzed. ..
  20. Lee C, Imig J, Edin M, Foley J, Degraff L, Bradbury J, et al. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice. FASEB J. 2010;24:3770-81 pubmed publisher
    ..We conclude that endothelial CYP epoxygenase function contributes to the regulation of blood pressure. ..
  21. Lehmann J, McKee D, Watson M, Willson T, Moore J, Kliewer S. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest. 1998;102:1016-23 pubmed
    ..These findings provide a molecular explanation for the ability of disparate chemicals to induce CYP3A4 levels and, furthermore, provide a basis for developing in vitro assays to aid in predicting whether drugs will interact in humans. ..
  22. Negishi M, Lindberg R, Burkhart B, Ichikawa T, Honkakoski P, Lang M. Mouse steroid 15 alpha-hydroxylase gene family: identification of type II P-450(15)alpha as coumarin 7-hydroxylase. Biochemistry. 1989;28:4169-72 pubmed
  23. Squires E, Negishi M. Reciprocal regulation of sex-dependent expression of testosterone 15 alpha-hydroxylase (P-450(15 alpha)) in liver and kidney of male mice by androgen. Evidence for a single gene. J Biol Chem. 1988;263:4166-71 pubmed
    ..Both Types I and II were repressed in male liver, which results in decreased levels of P-450(15 alpha). Androgen was responsible for the repression and expression of Type I in liver and kidney, but not Type II. ..
  24. Ryan R, Grimm S, Kedzie K, Halpert J, Philpot R. Cloning, sequencing, and functional studies of phenobarbital-inducible forms of cytochrome P450 2B and 4B expressed in rabbit kidney. Arch Biochem Biophys. 1993;304:454-63 pubmed
    ..Since P450 2B-B2 is catalytically distinct from the other forms, the metabolic profiles of phenotypes that include P450 2B-B2 might differ significantly from those of phenotypes that lack P450 2B-B2. ..
  25. Aida K, Moore R, Negishi M. Lack of the steroid 15 alpha-hydroxylase gene (Cyp2a-4) in wild mouse strain Mus spretus: rapid evolution of the P450 gene superfamily. Genomics. 1994;19:564-6 pubmed
    ..Evolutionarily, therefore, Cyp2a-5 is ancestral to Cyp2a-4. Moreover, the line to Cyp2a-4 descended as recently as 3 million years ago in an ancestral mouse. This evidence implies a rapid evolution of the P450 gene superfamily. ..
  26. Lindberg R, Burkhart B, Ichikawa T, Negishi M. The structure and characterization of type I P-450(15) alpha gene as major steroid 15 alpha-hydroxylase and its comparison with type II P-450(15) alpha gene. J Biol Chem. 1989;264:6465-71 pubmed
    ..The results indicated that Type I was the major steroid 15 alpha-hydroxylase. The differential 15 alpha OH-1 expression, therefore, determined the sexual dimorphism of the tissue-specific 15 alpha-hydroxylase activity in mice. ..
  27. Ichikawa T, Itakura T, Negishi M. Functional characterization of two cytochrome P-450s within the mouse, male-specific steroid 16 alpha-hydroxylase gene family: expression in mammalian cells and chimeric proteins. Biochemistry. 1989;28:4779-84 pubmed
  28. Gasser R, Negishi M, Philpot R. Primary structures of multiple forms of cytochrome P-450 isozyme 2 derived from rabbit pulmonary and hepatic cDNAs. Mol Pharmacol. 1988;33:22-30 pubmed
    ..A second hepatic cDNA library, constructed from mRNA from the liver of a rabbit treated with phenobarbital daily for 4 days, contained B0 clones. The sequence of one of these was found to be identical to that of the pulmonary B0 clones. ..
  29. Watkins R, Maglich J, Moore L, Wisely G, Noble S, Davis Searles P, et al. 2.1 A crystal structure of human PXR in complex with the St. John's wort compound hyperforin. Biochemistry. 2003;42:1430-8 pubmed
  30. Yokomori N, Kobayashi R, Moore R, Sueyoshi T, Negishi M. A DNA methylation site in the male-specific P450 (Cyp 2d-9) promoter and binding of the heteromeric transcription factor GABP. Mol Cell Biol. 1995;15:5355-62 pubmed
    ..We also conclude that GABP is a methylation-sensitive transcription factor and is a potential transcription activator of the male-specific Cyp 2d-9 promoter. ..
  31. Konno Y, Kamino H, Moore R, Lih F, Tomer K, Zeldin D, et al. The nuclear receptors constitutive active/androstane receptor and pregnane x receptor activate the Cyp2c55 gene in mouse liver. Drug Metab Dispos. 2010;38:1177-82 pubmed publisher
    ..Chronic PB treatment increased hepatic microsomal CYP2C55 protein and serum 19-HETE levels. These findings indicate that CAR and PXR may play a role in regulation of drug-induced synthesis of 19-HETE in the mouse. ..
  32. Goldstein J, Faletto M, Romkes Sparks M, Sullivan T, Kitareewan S, Raucy J, et al. Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans. Biochemistry. 1994;33:1743-52 pubmed
    ..These data indicate that 2C19 is the principal determinant of (S)-mephenytoin 4'-hydroxylase activity in human liver. ..
  33. Aida K, Negishi M. A trans-acting locus regulates transcriptional repression of the female-specific steroid 15 alpha-hydroxylase gene in male mice. J Mol Endocrinol. 1993;11:213-22 pubmed
  34. Jones S, Moore L, Shenk J, Wisely G, Hamilton G, McKee D, et al. The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol. 2000;14:27-39 pubmed publisher
    ..These data establish PXR as a promiscuous xenobiotic receptor that has diverged during evolution...
  35. Honkakoski P, Moore R, Gynther J, Negishi M. Characterization of phenobarbital-inducible mouse Cyp2b10 gene transcription in primary hepatocytes. J Biol Chem. 1996;271:9746-53 pubmed
    ..Belzil, A., Stoltz, C., and Anderson, A. (1995) Gene 158, 263-268). Our results indicate that sequences important for PB-induced transcription of Cyp2b10 gene are located in the distal promoter. ..
  36. Wu S, Moomaw C, Tomer K, Falck J, Zeldin D. Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart. J Biol Chem. 1996;271:3460-8 pubmed
    ..We propose that CYP2J2 is one of the enzymes responsible for epoxidation of endogenous arachidonic acid pools in human heart and that epoxyeicosatrienoic acids may, therefore, play important functional roles in cardiac physiology. ..
  37. Ma J, Qu W, Scarborough P, Tomer K, Moomaw C, Maronpot R, et al. Molecular cloning, enzymatic characterization, developmental expression, and cellular localization of a mouse cytochrome P450 highly expressed in kidney. J Biol Chem. 1999;274:17777-88 pubmed
    ..In light of the well documented effects of epoxyeicosatrienoic acids in modulating renal tubular transport processes, we postulate that CYP2J5 products play important functional roles in the kidney. ..
  38. Scarborough P, Ma J, Qu W, Zeldin D. P450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in extrahepatic tissues. Drug Metab Rev. 1999;31:205-34 pubmed
    ..This review details the emerging CYP2J subfamily of P450s and their role as catalysts of arachidonic acid metabolism. ..
  39. Sueyoshi T, Kawamoto T, Zelko I, Honkakoski P, Negishi M. The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. J Biol Chem. 1999;274:6043-6 pubmed
    ..Thus, activation of the repressed nuclear receptor CAR appears to be a versatile mediator that regulates PB induction of the CYP2B and other genes. ..
  40. van Birgelen A, Devito M, Akins J, Ross D, Diliberto J, Birnbaum L. Relative potencies of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls derived from hepatic porphyrin accumulation in mice. Toxicol Appl Pharmacol. 1996;138:98-109 pubmed
    ..However, the higher potencies of the mono-ortho-substituted PCBs have important implications for risk assessment of these compounds. ..
  41. Zeldin D, Foley J, Ma J, Boyle J, Pascual J, Moomaw C, et al. CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance. Mol Pharmacol. 1996;50:1111-7 pubmed
  42. Lakso M, Masaki R, Noshiro M, Negishi M. Structures and characterization of sex-specific mouse cytochrome P-450 genes as members within a large family. Duplication boundary and evolution. Eur J Biochem. 1991;195:477-86 pubmed
    ..All genes in that class contain the long ATTT repeat sequences in intron 1, which may have triggered a rapid gene conversion and/or stabilize the duplicated genes. ..
  43. Zeldin D, Foley J, Goldsworthy S, Cook M, Boyle J, Ma J, et al. CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance. Mol Pharmacol. 1997;51:931-43 pubmed
  44. Romkes M, Faletto M, Blaisdell J, Raucy J, Goldstein J. Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily. Biochemistry. 1991;30:3247-55 pubmed
    ..Clones 29c and 6b appear to be allelic variants (IIC18), differing by one nucleotide (one amino acid change) in the coding region. Clone 11a represents a full-length clone for a third new P450 (IIC19).(ABSTRACT TRUNCATED AT 250 WORDS) ..
  45. Yeowell H, McClellan Green P, Negishi M, Goldstein J. Characterization of a cDNA for the unexpressed form of cytochrome P-450g from the (-g) rat and differentiation of its mRNA from that of the (+g) phenotype using specific oligoprobes. Biochemistry. 1990;29:713-8 pubmed
    ..abstract truncated at 250 words) ..
  46. Kang H, Angers M, Beak J, Wu X, Gimble J, Wada T, et al. Gene expression profiling reveals a regulatory role for ROR alpha and ROR gamma in phase I and phase II metabolism. Physiol Genomics. 2007;31:281-94 pubmed
  47. McClellan Green P, Negishi M, Goldstein J. Characterization of a cDNA for rat P-450g, a highly polymorphic, male-specific cytochrome in the P-450IIC subfamily. Biochemistry. 1989;28:5832-9 pubmed
  48. Maglich J, Stoltz C, Goodwin B, Hawkins Brown D, Moore J, Kliewer S. Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol. 2002;62:638-46 pubmed
    ..These findings underscore the importance of these two nuclear receptors in defending the body against a broad array of potentially harmful xenobiotics. ..
  49. Sueyoshi T, Kobayashi R, Nishio K, Aida K, Moore R, Wada T, et al. A nuclear factor (NF2d9) that binds to the male-specific P450 (Cyp 2d-9) gene in mouse liver. Mol Cell Biol. 1995;15:4158-66 pubmed
    ..The results, therefore, indicate that the domestic Cyp 2d-9 gene can be regulated through a specific association of NF2d9 with SDI-A1. ..
  50. Ueda A, Hamadeh H, Webb H, Yamamoto Y, Sueyoshi T, Afshari C, et al. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol Pharmacol. 2002;61:1-6 pubmed
    ..Thus, CAR seems to have diverse roles, both as a positive and negative regulator, in the regulation of hepatic genes in response to PB beyond drug/steroid metabolism. ..
  51. Sanders J, Burka L, Chanas B, Matthews H. Comparative xenobiotic metabolism between Tg.AC and p53+/- genetically altered mice and their respective wild types. Toxicol Sci. 2001;61:54-61 pubmed