cytochrome p 450 enzyme system

Summary

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. ncbi Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies
    Nicola J Hewitt
    Scientific Writing Services, Wingertstrasse, Erzhausen, Germany
    Drug Metab Rev 39:159-234. 2007
  2. ncbi Evolution of supergene families associated with insecticide resistance
    Hilary Ranson
    Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
    Science 298:179-81. 2002
  3. ncbi Molecular mechanisms of metabolic resistance to synthetic and natural xenobiotics
    Xianchun Li
    Department of Entomology and BIO5, University of Arizona, Tucson, Arizona 85721, USA
    Annu Rev Entomol 52:231-53. 2007
  4. ncbi A single p450 allele associated with insecticide resistance in Drosophila
    P J Daborn
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    Science 297:2253-6. 2002
  5. ncbi Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression
    P Kuehl
    Department of Molecular and Cell Biology, University of Maryland at Baltimore, Baltimore, Maryland, USA
    Nat Genet 27:383-91. 2001
  6. ncbi Evolution of insect P450
    R Feyereisen
    UMR 1112, INRA and Université de Nice Sophia Antipolis, 06903 Sophia Antipolis, France
    Biochem Soc Trans 34:1252-5. 2006
  7. ncbi Cytochrome P450 and the individuality of species
    D R Nelson
    Department of Biochemistry, University of Tennessee, Memphis, Tennessee, 38163, USA
    Arch Biochem Biophys 369:1-10. 1999
  8. pmc Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids
    K Node
    Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division, Brigham and Women s Hospital and Harvard Medical School, 221 Longwood Avenue, LMRC 322, Boston, MA 02115, USA
    Science 285:1276-9. 1999
  9. ncbi Cytochromes P450 and insecticide resistance
    J G Scott
    Department of Entomology, Cornell University, Ithaca, NY 14853, USA
    Insect Biochem Mol Biol 29:757-77. 1999
  10. ncbi The Drosophila disembodied gene controls late embryonic morphogenesis and codes for a cytochrome P450 enzyme that regulates embryonic ecdysone levels
    V M Chavez
    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA
    Development 127:4115-26. 2000

Detail Information

Publications304 found, 100 shown here

  1. ncbi Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies
    Nicola J Hewitt
    Scientific Writing Services, Wingertstrasse, Erzhausen, Germany
    Drug Metab Rev 39:159-234. 2007
    ..We also report pharmaceutical perspectives of these topics and compare methods and interpretations for the drug development process...
  2. ncbi Evolution of supergene families associated with insecticide resistance
    Hilary Ranson
    Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
    Science 298:179-81. 2002
    ..The analyses also provide the means for identifying previously unknown molecules involved in fundamental biological processes such as development...
  3. ncbi Molecular mechanisms of metabolic resistance to synthetic and natural xenobiotics
    Xianchun Li
    Department of Entomology and BIO5, University of Arizona, Tucson, Arizona 85721, USA
    Annu Rev Entomol 52:231-53. 2007
    ..Differences in the selective regime imposed by allelochemicals and insecticides may account for the relative importance of regulatory or structural mutations in conferring resistance...
  4. ncbi A single p450 allele associated with insecticide resistance in Drosophila
    P J Daborn
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    Science 297:2253-6. 2002
    ..This allele is characterized by the insertion of an Accord transposable element into the 5' end of the Cyp6g1 gene...
  5. ncbi Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression
    P Kuehl
    Department of Molecular and Cell Biology, University of Maryland at Baltimore, Baltimore, Maryland, USA
    Nat Genet 27:383-91. 2001
    ....
  6. ncbi Evolution of insect P450
    R Feyereisen
    UMR 1112, INRA and Université de Nice Sophia Antipolis, 06903 Sophia Antipolis, France
    Biochem Soc Trans 34:1252-5. 2006
    ..In particular, insects appear to maintain a repertoire of mitochondrial P450 paralogues devoted to the response to environmental challenges...
  7. ncbi Cytochrome P450 and the individuality of species
    D R Nelson
    Department of Biochemistry, University of Tennessee, Memphis, Tennessee, 38163, USA
    Arch Biochem Biophys 369:1-10. 1999
    ..The biosynthesis of cholesterol in bacteria is discussed in relation to CYP51 as a lanosterol 14 alpha-demethylase. This enzyme may have been the first eukaryotic P450...
  8. pmc Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids
    K Node
    Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division, Brigham and Women s Hospital and Harvard Medical School, 221 Longwood Avenue, LMRC 322, Boston, MA 02115, USA
    Science 285:1276-9. 1999
    ..The inhibitory effects of EETs were independent of their membrane-hyperpolarizing effects, suggesting that these molecules play an important nonvasodilatory role in vascular inflammation...
  9. ncbi Cytochromes P450 and insecticide resistance
    J G Scott
    Department of Entomology, Cornell University, Ithaca, NY 14853, USA
    Insect Biochem Mol Biol 29:757-77. 1999
    ..The importance of these studies for development of effective insecticide resistance management strategies is discussed...
  10. ncbi The Drosophila disembodied gene controls late embryonic morphogenesis and codes for a cytochrome P450 enzyme that regulates embryonic ecdysone levels
    V M Chavez
    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA
    Development 127:4115-26. 2000
    ....
  11. ncbi Brassinosteroids rescue the deficiency of CYP90, a cytochrome P450, controlling cell elongation and de-etiolation in Arabidopsis
    M Szekeres
    Institute of Plant Biology, Hungarian Academy of Sciences, Szeged, Hungary
    Cell 85:171-82. 1996
    ..Brassinosteroids also compensate for different cell elongation defects of Arabidopsis det, cop, fus, and axr2 mutants, indicating that these steroids play an essential role in the regulation of plant development...
  12. ncbi Tumor-specific expression of cytochrome P450 CYP1B1
    G I Murray
    Department of Pathology, University of Aberdeen, Foresterhill, United Kingdom
    Cancer Res 57:3026-31. 1997
    ..These results provide the basis for the development of novel methods of cancer diagnosis based on the identification of CYP1B1 in tumor cells and the development of anticancer drugs that are selectively activated in tumors by CYP1B1...
  13. ncbi CYP306A1, a cytochrome P450 enzyme, is essential for ecdysteroid biosynthesis in the prothoracic glands of Bombyx and Drosophila
    Ryusuke Niwa
    Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5 1 5 Kashiwanoha, Kashiwa, Chiba 277 8562, USA
    J Biol Chem 279:35942-9. 2004
    ..These results strongly suggest that CYP306A1 functions as a carbon 25 hydroxylase and has an essential role in ecdysteroid biosynthesis during insect development...
  14. ncbi The Halloween genes code for cytochrome P450 enzymes mediating synthesis of the insect moulting hormone
    K F Rewitz
    Department of Life Sciences and Chemistry, Roskilde University, P O Box 260, 4000 Roskilde, Denmark
    Biochem Soc Trans 34:1256-60. 2006
    ..The results indicate that these Halloween genes are transcriptionally regulated to support the high biosynthetic activity that produces the cyclic ecdysteroid pulses triggering moulting...
  15. ncbi Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues
    Petr Pavek
    Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
    Curr Drug Metab 9:129-43. 2008
    ....
  16. ncbi Green leaf volatiles: hydroperoxide lyase pathway of oxylipin metabolism
    Kenji Matsui
    Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753 8515, Japan
    Curr Opin Plant Biol 9:274-80. 2006
    ....
  17. pmc Molecular and biochemical characterization of two P450 enzymes in the ecdysteroidogenic pathway of Drosophila melanogaster
    James T Warren
    Department of Biology, University of North Carolina, Chapel Hill, NC 27599 3280, USA
    Proc Natl Acad Sci U S A 99:11043-8. 2002
    ..Expression of dib and sad continues to be localized in this endocrine compartment during larval development, being maximal in both the late second and third instar larvae, about the time of the premolt peaks in the ecdysteroid titer...
  18. ncbi Cytochrome P450 gene polymorphism and cancer
    Jose A G Agundez
    Department of Pharmacology, Medical School, University of Extremadura, Avda de Elvas s n, E 06071, Badajoz, Spain
    Curr Drug Metab 5:211-24. 2004
    ..In addition, some recommendations on study design, in order to obtain more conclusive findings in further studies, are provided...
  19. ncbi The cytochrome P450 gene superfamily in Drosophila melanogaster: annotation, intron-exon organization and phylogeny
    N Tijet
    Department of Entomology, Forbes 410, P O Box 210036, The University of Arizona, Tucson 85721, USA
    Gene 262:189-98. 2001
    ..melanogaster, CYP6A2, has been functionally characterized. Gene organization appears to be a useful tool in the study of the regulation, the physiological role and the function of these P450s...
  20. ncbi Molecular evolution of the insect Halloween family of cytochrome P450s: phylogeny, gene organization and functional conservation
    Kim F Rewitz
    Department of Science, Systems and Models, Roskilde University, P O Box 260, 4000 Roskilde, Denmark
    Insect Biochem Mol Biol 37:741-53. 2007
    ..The results suggest that duplications of ancestral P450 genes that acquired novel functions may have been an important mechanism for evolving the ecdysteroidogenic pathway...
  21. ncbi Clinical importance of the cytochromes P450
    Daniel W Nebert
    Center for Environmental Genetics and Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH 45267 0056, USA
    Lancet 360:1155-62. 2002
    ..Mutations in many CYP genes cause inborn errors of metabolism and contribute to many clinically relevant diseases...
  22. ncbi Cytochrome P450 CYP307A1/Spook: a regulator for ecdysone synthesis in insects
    Toshiki Namiki
    Department of Integrated Biosciences, Rm 201, Graduate School of Frontier Sciences, The University of Tokyo, 5 1 5 Kashiwanoha, Kashiwa, Chiba 277 8562, Japan
    Biochem Biophys Res Commun 337:367-74. 2005
    ..These results suggest a difference in the ecdysone synthesis pathways during larval development in these insects...
  23. ncbi Cytochrome P-450 3A4: regulation and role in drug metabolism
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Annu Rev Pharmacol Toxicol 39:1-17. 1999
    ..The in vivo significance of these findings remains to be further established. In addition to more basic studies on P-450 3A4, several areas of practical interest to the pharmaceutical industry require development...
  24. ncbi An adult-specific CYP6 P450 gene is overexpressed in a pyrethroid-resistant strain of the malaria vector, Anopheles gambiae
    Dimitra Nikou
    Vector Biology Division, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
    Gene 318:91-102. 2003
    ..The isolation of An. gambiae cDNAs encoding cytochrome b(5) and nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH)-cytochrome P450 reductase cDNAs is also reported...
  25. ncbi Spook and Spookier code for stage-specific components of the ecdysone biosynthetic pathway in Diptera
    Hajime Ono
    The Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA
    Dev Biol 298:555-70. 2006
    ..These studies suggest an evolutionary split between Diptera and Lepidoptera in how the ecdysone biosynthetic pathway is regulated during development...
  26. ncbi A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer
    Christoph Sachse
    Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
    Carcinogenesis 23:1839-49. 2002
    ..This data suggests that heterocyclic amines do not play an important role in the aetiology of colorectal cancer but that exposure to other carcinogens such as polycyclic aromatic hydrocarbons may be important determinants of cancer risk...
  27. ncbi Insect P450 enzymes
    R Feyereisen
    Department of Entomology, University of Arizona, Tucson 85721, USA
    Annu Rev Entomol 44:507-33. 1999
    ..Polymorphisms in induction or constitutive expression allow insects to scan their P450 gene repertoire for the appropriate response to chemical insults, and these evolutionary pressures in turn maintain P450 diversity...
  28. ncbi Over expression of a cytochrome P450 (CYP6P9) in a major African malaria vector, Anopheles Funestus, resistant to pyrethroids
    D A Amenya
    Vector Control Reference Unit, National Institute for Communicable Diseases, NHLS, Private bag X 4, Sandringham, 2131, South Africa
    Insect Mol Biol 17:19-25. 2008
    ..This gene is genetically linked to a major locus associated with pyrethroid resistance in this A. funestus population...
  29. ncbi Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts
    Xinxin Ding
    Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201, USA
    Annu Rev Pharmacol Toxicol 43:149-73. 2003
    ..Current research activities on the characterization of CYP expression, function, and regulation in these tissues, as well as future research needs, are discussed...
  30. ncbi Evaluating the insecticide resistance potential of eight Drosophila melanogaster cytochrome P450 genes by transgenic over-expression
    Phillip J Daborn
    Centre for Environmental Stress and Adaptation Research CESAR, Department of Genetics, Bio21 Molecular and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia
    Insect Biochem Mol Biol 37:512-9. 2007
    ..No increased survival on any insecticide was detected for flies over-expressing either Cyp6a2, Cyp6a8, Cyp6t3, Cyp6a19 or Cyp6a23...
  31. ncbi Increased transcription of CYP6D1 causes cytochrome P450-mediated insecticide resistance in house fly
    N Liu
    Department of Entomology, Cornell University, Ithaca, New York 14853 0901, USA
    Insect Biochem Mol Biol 28:531-5. 1998
    ..The increased rate of transcription of CYP6D1 in the resistant strain (LPR) is controlled by two factors: one on autosome 1 and another on autosome 2...
  32. ncbi CYP3A4 variant alleles in white individuals with low CYP3A4 enzyme activity
    Elena Garcia-Martin
    Department of Biochemistry, School of Biological Sciences, University of Extremadura, Badajoz, Spain
    Clin Pharmacol Ther 71:196-204. 2002
    ..Our objective was to evaluate the presence of CYP3A4 gene variants in white individuals with low CYP3A4 enzyme activity...
  33. ncbi Functional genomics of P450s
    Mary A Schuler
    Department of Cell and Structural Biology, University of Illinois, Urbana Champaign, Illinois 61801, USA
    Annu Rev Plant Biol 54:629-67. 2003
    ..The examples of assigned P450 activities that are spread throughout this review highlight the importance of understanding and utilizing P450 sequences as markers for linking biochemical pathway responses to physiological processes...
  34. ncbi Arabidopsis local resistance to Botrytis cinerea involves salicylic acid and camalexin and requires EDS4 and PAD2, but not SID2, EDS5 or PAD4
    Simone Ferrari
    Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
    Plant J 35:193-205. 2003
    ..cinerea requires ethylene-, jasmonate-, and SA-mediated signaling, that the SA affecting this resistance does not require ICS1 and is likely synthesized via PAL, and that camalexin limits lesion development...
  35. ncbi Identification of the retinoic acid-inducible all-trans-retinoic acid 4-hydroxylase
    J A White
    Cancer Research Laboratories, Queen s University, Kingston, Ontario, K7L 3N6 Canada
    J Biol Chem 271:29922-7. 1996
    ..P450RAI represents the first enzymatic component of RA metabolism to be isolated and characterized at the molecular level and provides key insight into regulation of retinoid homeostasis...
  36. ncbi Summary of information on human CYP enzymes: human P450 metabolism data
    Slobodan Rendic
    Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia
    Drug Metab Rev 34:83-448. 2002
    ..gentest.com) enabling the readers easy and quick approach to the latest updates on human CYP metabolic reactions...
  37. pmc Hydroperoxide lyase depletion in transgenic potato plants leads to an increase in aphid performance
    G Vancanneyt
    , Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, , 28049 Madrid, Spain
    Proc Natl Acad Sci U S A 98:8139-44. 2001
    ..Thus, HPL-catalyzed production of C6 aldehydes may be a key step of a built-in resistance mechanism of plants against some sucking insect pests...
  38. ncbi Genome sequence of the lignocellulose degrading fungus Phanerochaete chrysosporium strain RP78
    Diego Martinez
    US DOE Joint Genome Institute, Walnut Creek, California 94598, USA
    Nat Biotechnol 22:695-700. 2004
    ..This genome provides a high quality draft sequence of a basidiomycete, a major fungal phylum that includes important plant and animal pathogens...
  39. ncbi ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment
    Severine Crettol
    Unite de Biochimie et Psychopharmacologie Clinique, Centre de Neurosciences Psychiatriques, Département de Psychiatrie Centre Hospitalier Universitaire Vaudois, Hôpital de Cery, Prilly Lausanne, Switzerland
    Clin Pharmacol Ther 80:668-81. 2006
    ..The in vivo implication of various cytochrome P450 (CYP) isoforms and of P-glycoprotein on methadone kinetics is unclear. We aimed to thoroughly examine the genetic factors influencing methadone kinetics and response to treatment...
  40. ncbi World-wide survey of an Accord insertion and its association with DDT resistance in Drosophila melanogaster
    F Catania
    Institut fur Tierzucht und Genetik, University of Wien, Josef Baumann Gasse 1, 1210 Wien, Austria
    Mol Ecol 13:2491-504. 2004
    ..This study confirms that hitchhiking mapping can be used to identify beneficial mutations in natural populations...
  41. ncbi In vitro-in vivo scaling of CYP kinetic data not consistent with the classical Michaelis-Menten model
    J B Houston
    School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, United Kingdom
    Drug Metab Dispos 28:246-54. 2000
    ..Finally, the consequences of ignoring atypical Michaelis-Menten kinetic relationships are examined, and the inconsistencies reported for both different substrates and sources of recombinant CYP3A noted...
  42. ncbi Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers
    W Ridtitid
    Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Thailand
    J Pharm Pharmacol 52:1265-9. 2000
    ..Simultaneous use of rifampin and mefloquine should be avoided to optimize the therapeutic efficacy of mefloquine and prevent the risk of Plasmodium falciparum resistance in malarial treatment...
  43. ncbi Cytochromes P450 for engineering herbicide tolerance
    D Werck-Reichhart
    Dept of Cellular and Molecular Enzymology, Institute of Plant Molecular Biology, Centre National de la Recherche Scientifique UPR 406, 28 rue Goethe, 67083 Strasbourg Cedex, France
    Trends Plant Sci 5:116-23. 2000
    ....
  44. ncbi Identification, characterization and developmental expression of Halloween genes encoding P450 enzymes mediating ecdysone biosynthesis in the tobacco hornworm, Manduca sexta
    Kim F Rewitz
    Department of Life Sciences and Chemistry, Roskilde University, P O Box 260, 4000 Roskilde, Denmark
    Insect Biochem Mol Biol 36:188-99. 2006
    ..The consistent expression of the Halloween genes confirms the importance of the prothoracic glands in pupal-adult development. These studies establish Manduca as an excellent model for examining the regulation of the Halloween genes...
  45. ncbi Tumour cytochrome P450 and drug activation
    L H Patterson
    Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 9 39 Brunswick Square, London, WC1N 1AX, UK
    Curr Pharm Des 8:1335-47. 2002
    ..Also of interest is the bioreductive antitumour prodrug AQ4N, a CYP3A substrate that is activated to a cytotoxic metabolite specifically in hypoxic tumour regions...
  46. ncbi Isolation and characterization of the human cytochrome P450 CYP1B1 gene
    Y M Tang
    Department of Pharmacology and Toxicology, Purdue University, West Lafayette, Indiana 47907, USA
    J Biol Chem 271:28324-30. 1996
    ....
  47. ncbi Localization of rat cytochrome P450 in various tissues and comparison of arachidonic acid metabolism by rat P450 with that by human P450 orthologs
    Susumu Imaoka
    Nanobiotechnology Research Center and Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Hyogo, Japan
    Drug Metab Pharmacokinet 20:478-84. 2005
    ..A systematic analysis of P450 expression in various tissues and of its catalytic property may provide valuable information on the physiological roles of P450s in each tissue...
  48. ncbi Differential expression of the detoxification genes in the different life stages of the malaria vector Anopheles gambiae
    C Strode
    Vector Research Group, Liverpool School of Tropical Medicine, Liverpool, UK
    Insect Mol Biol 15:523-30. 2006
    ..The expression profile of each of these genes and the information this data provides on putative functions of the mosquito detoxification enzymes is discussed...
  49. ncbi Functional analysis of six different polymorphic CYP1B1 enzyme variants found in an Ethiopian population
    Eleni Aklillu
    Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
    Mol Pharmacol 61:586-94. 2002
    ..1 enzyme. The results emphasize the necessity of a complete haplotype analysis of enzyme variants for evaluation of functional consequences in vivo and for analyses of genetic polymorphisms in relation to, for example, cancer incidence...
  50. ncbi CYP98A3 from Arabidopsis thaliana is a 3'-hydroxylase of phenolic esters, a missing link in the phenylpropanoid pathway
    G Schoch
    Department of Plant Stress Response, Institute of Plant Molecular Biology, CNRS UPR 2357, 28 rue Goethe, F 67083 Strasbourg cedex, France
    J Biol Chem 276:36566-74. 2001
    ..This hydroxylation occurs on depsides, the function of which was so far not understood, revealing an additional and unexpected level of networking in lignin biosynthesis...
  51. ncbi Two independent duplications forming the Cyp307a genes in Drosophila
    Tamar Sztal
    Department of Genetics, Bio21 Molecular and Biotechnology Institute, The University of Melbourne, Vic, 3010, Australia
    Insect Biochem Mol Biol 37:1044-53. 2007
    ..Cyp307a3 appears to encode a functional gene product and is expressed in a different spatial and temporal manner to Cyp307a1. This suggests some level of functional divergence between the Cyp307a paralogs in different Drosophila species...
  52. pmc The Arabidopsis cytochrome P450 CYP86A1 encodes a fatty acid omega-hydroxylase involved in suberin monomer biosynthesis
    Rene Höfer
    Institute of Cellular and Molecular Botany, University of Bonn, Kirschallee 1, D 53115 Bonn, Germany
    J Exp Bot 59:2347-60. 2008
    ..Transgenic expression of CYP86A1 fused to GFP distributed CYP86A1 to the endoplasmic reticulum, indicating that suberin monomer biosynthesis takes place in this sub-cellular compartment before intermediates are exported in the apoplast...
  53. ncbi Expression of the retinoic acid catabolising enzyme CYP26B1 in the chick embryo and its regulation by retinoic acid
    Susan Reijntjes
    MRC Centre for Developmental Neurobiology, 4th Floor, New Hunt s House, King s College London, Guy s Campus, London Bridge, SE1 1UL, London, UK
    Gene Expr Patterns 3:621-7. 2003
    ..In the absence of RA, Cyp26B1 is only expressed in the hindbrain and fails to be expressed in all the other regions of the embryo, most dramatically in the trunk. Adding back RA rescues Cyp26B1 expression...
  54. ncbi DDT resistance in Drosophila correlates with Cyp6g1 over-expression and confers cross-resistance to the neonicotinoid imidacloprid
    P Daborn
    Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
    Mol Genet Genomics 266:556-63. 2001
    ..We are now testing the hypothesis that resistance to both compounds is associated with over-expression of this P450 gene...
  55. ncbi Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells
    Caroline Aninat
    Institut National de la Santé et de la Recherche Médicale INSERM U620, Universite de Rennes 1, France
    Drug Metab Dispos 34:75-83. 2006
    ....
  56. ncbi Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment
    Severine Crettol
    Unite de Biochimie et Psychopharmacologie Clinique, Centre des Neurosciences Psychiatriques, Departement universitaire de psychiatrie adulte, Hôpital de Cery, Lausanne, Switzerland
    Clin Pharmacol Ther 78:593-604. 2005
    ..We aimed to determine the influence of CYP2B6, CYP2C9, and CYP2C19 genetic polymorphism on methadone pharmacokinetics and on the response to treatment...
  57. ncbi Expression and regulation of xenobiotic-metabolizing cytochrome P450 (CYP) enzymes in human lung
    Janne Hukkanen
    Department of Pharmacology, University of Oulu, Finland
    Crit Rev Toxicol 32:391-411. 2002
    ..Problems in animal to human lung toxicity extrapolation and several specific aspects requiring more detailed assessment are identified...
  58. ncbi Cloning, heterologous expression, and functional characterization of 5-epi-aristolochene-1,3-dihydroxylase from tobacco (Nicotiana tabacum)
    L Ralston
    Department of Agronomy, University of Kentucky, Lexington, Kentucky 40546-0091, USA
    Arch Biochem Biophys 393:222-35. 2001
    ....
  59. ncbi Feedback mechanisms regulate retinoic acid production and degradation in the zebrafish embryo
    Betsy Dobbs-McAuliffe
    Department of Cell Biology, Duke University Medical Center, Box 3020, Durham, NC 27710, USA
    Mech Dev 121:339-50. 2004
    ..These data demonstrate that the feedback mechanisms regulating production and degradation of RA must be considered in any experiments altering levels of RA in the developing vertebrate embryo...
  60. ncbi Regulation of retinoic acid distribution is required for proximodistal patterning and outgrowth of the developing mouse limb
    Kenta Yashiro
    Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
    Dev Cell 6:411-22. 2004
    ..These observations suggest that RA acts as a morphogen to determine proximodistal identity, and that CYP26B1 prevents apoptosis and promotes chondrocyte maturation, in the developing limb...
  61. ncbi Cytochrome P450 pharmacogenetics and cancer
    C Rodriguez-Antona
    Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Center CNIO, Madrid, Spain
    Oncogene 25:1679-91. 2006
    ..This review gives an up-to-date description of our current knowledge in these areas...
  62. pmc Database analyses for the prediction of in vivo drug-drug interactions from in vitro data
    Kiyomi Ito
    School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PL, UK
    Br J Clin Pharmacol 57:473-86. 2004
    ..The aim of this study was to construct a database for the prediction of drug-drug interactions from in vitro data and to evaluate the use of the various estimates for the inhibitor concentrations in the term [I]/K(i)...
  63. ncbi Flavones and flavone synthases
    Stefan Martens
    Institut fur Pharmazeutische Biologie, Philipps Universitat Marburg, Germany
    Phytochemistry 66:2399-407. 2005
    ....
  64. pmc Genome-wide characterization of the lignification toolbox in Arabidopsis
    Jeroen Raes
    Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, Technologiepark 927, B 9052 Gent, Belgium
    Plant Physiol 133:1051-71. 2003
    ..Together, these data describe the full complement of monolignol biosynthesis genes in Arabidopsis, provide a unified nomenclature, and serve as a basis for further functional studies...
  65. pmc CYP4F2 genetic variant alters required warfarin dose
    Michael D Caldwell
    Department of Surgery, Marshfield Clinic, Marshfield, WI, USA
    Blood 111:4106-12. 2008
    ..Genetic variation of CYP4F2 was associated with a clinically relevant effect on warfarin requirement...
  66. ncbi Point mutations associated with insecticide resistance in the Drosophila cytochrome P450 Cyp6a2 enable DDT metabolism
    Marcel Amichot
    Unité Mixte de Recherche 1112, Institut National de la Recherche Agronomique, Sophia Antipolis, France
    Eur J Biochem 271:1250-7. 2004
    ..Thus this area, including helix J, is important for the structure and activity of CYP6A2. Furthermore, we show here that point mutations in a cytochrome P450 can have a prominent role in insecticide resistance...
  67. ncbi Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes
    Ajay Madan
    XenoTech, LLC, 16825 West 116th Street, Lenexa, KS 66219, USA
    Drug Metab Dispos 31:421-31. 2003
    ....
  68. ncbi Pharmacogenomics of human liver cytochrome P450 oxidoreductase: multifactorial analysis and impact on microsomal drug oxidation
    Ana M Gomes
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Auerbachstrasse 112, 70376 Stuttgart, Germany
    Pharmacogenomics 10:579-99. 2009
    ..We investigated genetic and nongenetic POR variability and its impact on drug-oxidation activities in human liver microsomes...
  69. pmc Expression of the cytochrome P450s, CYP6P3 and CYP6M2 are significantly elevated in multiple pyrethroid resistant populations of Anopheles gambiae s.s. from Southern Benin and Nigeria
    Rousseau F Djouaka
    International Institute of Tropical Agriculture, Cotonou, 08BP0932, Benin
    BMC Genomics 9:538. 2008
    ..The mosquitoes were sampled from a variety of breeding sites in a preliminary attempt to investigate the role of contamination of mosquito breeding sites in selecting for resistance in adult mosquitoes...
  70. ncbi Over-expression of cytochrome P450 CYP6CM1 is associated with high resistance to imidacloprid in the B and Q biotypes of Bemisia tabaci (Hemiptera: Aleyrodidae)
    Iris Karunker
    Department of Entomology, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot, Israel
    Insect Biochem Mol Biol 38:634-44. 2008
    ..tabaci, and the CYP6CM1 gene as a leading target for DNA-based screening for resistance to imidacloprid and possibly other neonicotinoids in field populations...
  71. pmc Cytochrome P450 CYP1B1 determines susceptibility to 7, 12-dimethylbenz[a]anthracene-induced lymphomas
    J T Buters
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 96:1977-82. 1999
    ....
  72. ncbi Expression of drug metabolizing enzymes in hepatocyte-like cells derived from human embryonic stem cells
    Monica Ek
    Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, SE 17177 Stockholm, Sweden
    Biochem Pharmacol 74:496-503. 2007
    ....
  73. ncbi Expression of Cyp6g1 and Cyp12d1 in DDT resistant and susceptible strains of Drosophila melanogaster
    R A Festucci-Buselli
    Department of Entomology, Purdue University, 1158 Smith Hall, West Lafayette, IN 47907 1158, USA
    Insect Mol Biol 14:69-77. 2005
    ..Our data support the hypothesis that there is evolutionary plasticity in the expression patterns of P450s associated with metabolic pesticide resistance...
  74. ncbi Structural model and functional characterization of the Bemisia tabaci CYP6CM1vQ, a cytochrome P450 associated with high levels of imidacloprid resistance
    Iris Karunker
    Department of Entomology, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot, Israel
    Insect Biochem Mol Biol 39:697-706. 2009
    ..2 pmol/min/pmol P450, K(m) = 36 microM). The data identify CYP6CM1vQ as a principle target for inhibitor design, aimed at inactivating insecticide-metabolizing P450s in natural insect pest populations...
  75. ncbi Metabolism of imidacloprid and DDT by P450 CYP6G1 expressed in cell cultures of Nicotiana tabacum suggests detoxification of these insecticides in Cyp6g1-overexpressing strains of Drosophila melanogaster, leading to resistance
    Nicole Joussen
    Institute of Biology V, RWTH Aachen University, Worringerweg 1, D 52056 Aachen, Germany
    Pest Manag Sci 64:65-73. 2008
    ..melanogaster are resistant to a wide range of chemically diverse insecticides, including DDT and imidacloprid. However, up to now there has been no evidence that the CYP6G1 enzyme metabolises any of these compounds...
  76. pmc Cloning of the pleiotropic T locus in soybean and two recessive alleles that differentially affect structure and expression of the encoded flavonoid 3' hydroxylase
    Gracia Zabala
    Department of Crop Sciences, University of Illinois, Urbana, Illinois 61801, USA
    Genetics 163:295-309. 2003
    ....
  77. pmc Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism
    J A White
    Cytochroma Incorporated, Biosciences Complex, 116 Barrie Street, and Department of Biochemistry, Medicine, Queen s University, Kingston, ON, K7L 3N6, Canada
    Proc Natl Acad Sci U S A 97:6403-8. 2000
    ..The high level of expression of P450RAI-2, particularly in the cerebellum and pons of human adult brain, suggests a unique role for this enzyme in the protection of specific tissues from exposure to retinoids...
  78. pmc CYP15A1, the cytochrome P450 that catalyzes epoxidation of methyl farnesoate to juvenile hormone III in cockroach corpora allata
    C Helvig
    Department of Entomology, University of Arizona, Tucson, AZ 85721, USA
    Proc Natl Acad Sci U S A 101:4024-9. 2004
    ..Heterologously expressed CYP15A1 from D. punctata or its ortholog from economically important species may be useful in the design and screening of selective insect control agents...
  79. ncbi A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid
    Mohammed Taimi
    Cytochroma Inc, Markham, Ontario L3R 8E4, Canada
    J Biol Chem 279:77-85. 2004
    ..CYP26C1 is not widely expressed in the adult but is inducible by RA in HPK1a, transformed human keratinocyte cell lines. This third CYP26 member may play a specific role in catabolizing both all-trans and 9-cis isomers of RA...
  80. ncbi Metabolic diversification--independent assembly of operon-like gene clusters in different plants
    Ben Field
    Department of Metabolic Biology, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK
    Science 320:543-7. 2008
    ..Thus, selection pressure may act during the formation of certain plant metabolic pathways to drive gene clustering...
  81. pmc Protein stability promotes evolvability
    Jesse D Bloom
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 103:5869-74. 2006
    ..Our work establishes a crucial link between protein stability and evolution. We show that we can exploit this link to discover protein functions, and we suggest how natural evolution might do the same...
  82. pmc Cytochromes P450: a success story
    D Werck-Reichhart
    Department of Stress Response, Institute of Plant Molecular Biology, CNRS FRE2161, rue Goethe, 67083 Strasbourg Cedex, France
    Genome Biol 1:REVIEWS3003. 2000
    ..P450 enzymes catalyze many reactions that are important in drug metabolism or that have practical applications in industry; their economic impact is therefore considerable...
  83. ncbi Molecular genetics of primary congenital glaucoma
    M Sarfarazi
    Department of Surgery, University of Connecticut Health Center, Farmington 06030 1110, USA
    Eye (Lond) 14:422-8. 2000
    ..Revealing the identity of this molecule is our major objective since it can lead to as yet unknown biochemical cascades controlling the terminal stages of anterior chamber angle development...
  84. ncbi Identification of beta-amyrin and sophoradiol 24-hydroxylase by expressed sequence tag mining and functional expression assay
    Masaaki Shibuya
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan
    FEBS J 273:948-59. 2006
    ..In addition, substrate specificity with the obtained P450 hydroxylase indicates the two possible biosynthetic routes from triterpene-monool to triterpene-triol...
  85. pmc The maize Dwarf3 gene encodes a cytochrome P450-mediated early step in Gibberellin biosynthesis
    R G Winkler
    Department of Plant Sciences, University of Arizona, Tucson 85721, USA
    Plant Cell 7:1307-17. 1995
    ..Analysis of D3 mRNA showed that the D3 transcript is expressed in roots, developing leaves, the vegetative meristem, and suspension culture cells. We detected reduced D3 mRNA levels in the mutant allele d3.5...
  86. pmc A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations
    E Mellado
    Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Carretera Majadahonda Pozuelo Km2, 28220 Madrid, Spain
    Antimicrob Agents Chemother 51:1897-904. 2007
    ....
  87. ncbi The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution
    Jason K Yano
    Department of Molecular and Experimental Medicine and Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 279:38091-4. 2004
    ..The structure of P450 3A4 should facilitate a better understanding of the substrate selectivity of the enzyme...
  88. ncbi Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2
    L A McLaughlin
    Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom
    Insect Mol Biol 17:125-35. 2008
    ..Several compounds were shown to be substrates, suggesting that CYP6Z2 has broad substrate specificity and plays an important chemo-protective role during the herbivorous phase of the life-cycle...
  89. ncbi Skin retinoid concentrations are modulated by CYP26AI expression restricted to basal keratinocytes in normal human skin and differentiated 3D skin models
    Ruth Heise
    Department of Dermatology and Allergology, University Hospital of the RWTH Aachen, Aachen, Germany
    J Invest Dermatol 126:2473-80. 2006
    ..In light of our prior studies documenting the functional activity of RA metabolites, expression of CYP26 in the sebaceous gland epithelium supports the suggestion that altered RA metabolism may be involved in the pathogenesis of acne...
  90. pmc A deficit of detoxification enzymes: pesticide sensitivity and environmental response in the honeybee
    C Claudianos
    Research School of Biological Sciences, Australian National University, Canberra, ACT, Australia
    Insect Mol Biol 15:615-36. 2006
    ..On the other hand there are some recent radiations in CYP6, CYP9 and certain CCE clades in A. mellifera that could be associated with the evolution of the hormonal and chemosensory processes underpinning its highly organized eusociality...
  91. ncbi Association of CYP2C9 genotypes leading to high enzyme activity and colorectal cancer risk
    C Martinez
    Department of Pharmacology, Medical School, University of Extremadura, Avda de Elvas s n, E 06071, Badajoz, Spain
    Carcinogenesis 22:1323-6. 2001
    ..In addition, the key role of CYP2C9 in the metabolic inactivation of non-steroidal anti- inflammatory drugs could diminish the protective effect of these drugs against colorectal cancer...
  92. ncbi The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans
    P B Danielson
    University of Denver, Department of Biological Sciences, Denver, Colorado 80210, USA
    Curr Drug Metab 3:561-97. 2002
    ..This review examines the latest advances in our understanding of human cytochrome p450s...
  93. ncbi The genome of the model beetle and pest Tribolium castaneum
    Stephen Richards
    Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
    Nature 452:949-55. 2008
    ..Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control...
  94. ncbi Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study
    Wiebke Arlt
    Division of Medical Sciences, Institute of Biomedical Research, Medical School, Birmingham B15 2TT, UK
    Lancet 363:2128-35. 2004
    ..We aimed to investigate the underlying molecular basis of congenital adrenal hyperplasia with apparent combined P450C17 and P450C21 deficiency in affected children...
  95. ncbi Dietary flavonoids: effects on xenobiotic and carcinogen metabolism
    Young Jin Moon
    Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY 14260 1200, USA
    Toxicol In Vitro 20:187-210. 2006
    ..As well, flavonoids may also interact with chemotherapeutic drugs used in cancer treatment through the induction or inhibition of their metabolism...
  96. ncbi Interaction between P450 eicosanoids and nitric oxide in the control of arterial tone in mice
    Hantz C Hercule
    Charite Campus Buch, Franz Volhard Clinic ECRC, Berlin, Germany
    Arterioscler Thromb Vasc Biol 29:54-60. 2009
    ..We identified a novel interaction between EETs and endothelial NO release using soluble epoxide hydrolase (sEH) -/- and +/+ mice...
  97. ncbi Cytochrome P450 mono-oxygenases in conifer genomes: discovery of members of the terpenoid oxygenase superfamily in spruce and pine
    B Hamberger
    Michael Smith Laboratories, University of British Columbia, 301 2185 East Mall, Vancouver, BC, Canada V6T 1Z4
    Biochem Soc Trans 34:1209-14. 2006
    ..This paper will focus on the discovery of conifer CYPs associated with diterpene metabolism and CYP with possible functions in the formation of GA, BR, and ABA in conifers...
  98. pmc Cis-regulatory elements in the Accord retrotransposon result in tissue-specific expression of the Drosophila melanogaster insecticide resistance gene Cyp6g1
    Henry Chung
    Centre for Environmental and Stress Adaptation Research, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia
    Genetics 175:1071-7. 2007
    ..This study provides a significant example of how changes in tissue-specific gene expression caused by transposable-element insertions can contribute to adaptation...
  99. ncbi Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster
    Lawrence I Gilbert
    The University of North Carolina at Chapel Hill, CB 3280, Coker Hall, Chapel Hill, NC 27599 3280, USA
    Mol Cell Endocrinol 215:1-10. 2004
    ..Shade is present in several tissues as expected while disembodied and shadow are restricted to the ring gland. The paradigm used should allow us to define the enzymes mediating the entire ecdysteroid biosynthetic pathway...
  100. ncbi Molecular analysis of multiple cytochrome P450 genes from the malaria vector, Anopheles gambiae
    H Ranson
    Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
    Insect Mol Biol 11:409-18. 2002
    ..Eighteen new A. gambiae Cyp4 P450 genes were identified using degenerate PCR primers, cDNAs were detected for ten and in situ locations for thirteen members of this gene family...
  101. ncbi Retinoid signaling determines germ cell fate in mice
    Josephine Bowles
    Division of Genetics and Developmental Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
    Science 312:596-600. 2006
    ..Thus, precise regulation of retinoid levels during fetal gonad development provides the molecular control mechanism that specifies germ cell fate...

Research Grants77

  1. MOLECULAR MECHANISMS OF COMPLEX MIXTURE TOXICITY
    Alvaro Puga; Fiscal Year: 2013
    ....
  2. Microsomal Cytochromes P450 and their Interactions with their Redox Partners
    Lucy A Waskell; Fiscal Year: 2013
    ....
  3. Biochemical Characterization of Cytochrome b5 Reductase in Candida albicans
    MARY JOLENE PATRICIA HOLLOWAY; Fiscal Year: 2010
    ..I will also learn new techniques used in biochemistry and proteomics, such as mass spectrometry, protein pull-down assays, and other methods involved in the characterization of proteins. ..
  4. StAR expression: Integration of Transcription with regulation via the mRNA 3'UTR
    COLIN ROBERT JEFCOATE; Fiscal Year: 2012
    ..TIS11b regulation is present in other tissues that make steroids (testis). Deficiency in this mRNA regulator may lead to more sluggish responses to ACTH and stress as well as abnormal cortisol output. ..
  5. Electron Transfer in Iron and Copper Proteins
    Jay R Winkler; Fiscal Year: 2013
    ..Efforts will focus on oxidative generation of Compounds I and II in cytochromes P450 (Aim 3) and a bacterial enzyme that exhibits NOS-like reactivity (Aim 4). ..
  6. Early Disease Biomarkers of PCB-exposed Human Population
    Sisir K Dutta; Fiscal Year: 2010
    ....
  7. Influence of Heme on Hepatic Cytochrome P450 Turnover
    Maria Almira Correia; Fiscal Year: 2013
    ..Moreover, such global alterations of hepatic P450 turnover would also rationalize the impaired drug clearance clinically observed in porphyric patients. ..
  8. Non-Hodgkin lymphoma in women: reproductive, hormonal and genetic factors
    Paige M Bracci; Fiscal Year: 2011
    ....
  9. HEPATIC DEGRADATION OF CYTOCHROME P450 ENZYMES
    Maria Almira Correia; Fiscal Year: 2013
    ....
  10. Activating liver carcinogens in yeast by expressing CYP450 polymorphisms
    MICHAEL THOMAS FASULLO; Fiscal Year: 2010
    ..Ultimately, the information will aid public health practitioners and clinicians to identify which individuals are at highest risk for liver cancer, and guide prevention and early detection efforts. ..
  11. Creation of hyperactive transposons for mutagenesis in rodents
    Eric M Ostertag; Fiscal Year: 2011
    ..Thus, if successful, this project would benefit many goals of public health by making the production of mutations in the rat that model human diseases readily accessible to the research community. ..
  12. Molecular &Cellular Effects of Human Mutations in Cytochrome P450 Reductase
    Satya Prakash Panda; Fiscal Year: 2013
    ..Identification of new human polymorphisms will continue to determine possible downstream biomarkers of POR deficiency is a potential outcome. ..
  13. Genetic Determinants of the Response to Thienopyridine Therapy
    Jessica L Mega; Fiscal Year: 2013
    ..The TIMI Study Group also offers the appropriate training environment to provide Dr. Mega with the skills needed to lead the multicenter clinical trial described in Aim 3. ..
  14. Human hepatocytes for drug toxicity screening from Cardiac Death Donor livers
    Mark G Clemens; Fiscal Year: 2012
    ..should allow us to quickly translate this innovative technology into a commercially viable product. ..
  15. Novel Catalases and their Products
    Alan R Brash; Fiscal Year: 2013
    ..By uncovering the details of how different enzymes deal with oxidants and how they relate or differ from each other this project will improve our understanding of oxidative stress, which will ultimately help control it. ..
  16. Developing a prediction model for vincristine-induced peripheral neuropathy
    Jamie L Renbarger; Fiscal Year: 2010
    ..Once the correlation between genetics and vincristine neurotoxicity fully elucidated, it will be possible to individualize vincristine dosing using genetic information to optimize therapeutic efficacy while minimizing toxicity. ..
  17. Hepatic CYP enzymes and host-pathogen interactions
    Edward T Morgan; Fiscal Year: 2013
    ..This project will increase our understanding of how liver metabolism changes during infection or inflammation, and may discover new strategies to treat infectious and inflammatory diseases. ..
  18. PERINATAL MECHANISMS OF DETOXIFICATION
    Eric F Johnson; Fiscal Year: 2013
    ..Additionally, we will address how genetic deficiencies of this capacity affect susceptibility to hypertension due to renal and liver dysfunction. ..
  19. Eicosanoids and Endothelial Cell Dysfunction
    Gadiparthi N Rao; Fiscal Year: 2013
    ....
  20. NOVEL HIGH THROUGHPUT PLATFORM FOR SCREENING CYTOCHROME P450 INDUCTION
    MARIA INES MORANO; Fiscal Year: 2013
    ....
  21. Genetic Susceptibility Factors in Porphyria Cutanea Tarda (PCT)
    Karl Anderson; Fiscal Year: 2009
    ..This study and projects which follow will lead to a better understanding of PCT and also contribute to knowledge about how agents such as alcohol and hepatitis C interact with genetic factors in causing human liver diseases. ..
  22. CYP1B1, NF-kB , and Regulation of Angiogenesis
    TAMMY LYNN PALENSKI; Fiscal Year: 2012
    ..A better understanding of how angiogenesis is regulated will aid in development of new and more effective therapies for these blinding diseases, as well as other diseases with a neovascular component. ..
  23. Does the extreme variability of methadone metabolism have an epigenetic cause?
    Gavin R Schnitzler; Fiscal Year: 2010
    ....
  24. Modulation of Neonatal Hyperoxic Lung Injury by the Aryl Hydrocarbon Receptor
    Binoy Shivanna; Fiscal Year: 2013
    ..I anticipate that the results will support my hypotheses, which will lead to novel strategies in the prevention and treatment of BPD in premature infants. ..
  25. Genomic profiling of yeast resistance to AFB1, a P450-activated carcinogen
    MICHAEL THOMAS FASULLO; Fiscal Year: 2013
    ..The project will be a valuable training tool in systems and computational biology. ..
  26. Role of Mitochondrial Aldehyde Dehydrogenases in Ethanol Metabolism and Toxicity
    Vasilis Vasiliou; Fiscal Year: 2010
    ..This will be accomplished by studying the formation of heterotetramers using recombinant proteins and cell lines expressing these proteins. ..
  27. Polymorphisms of estrogen-metabolizing genes in kidney cancer
    Yuichiro Tanaka; Fiscal Year: 2013
    ..Such information can lead to the identification of Veterans with higher risk for RCC. Proposed research may also lead to implications for possible therapy for RCC. ..
  28. Oxygen Sensors and P450 Monooxygenases in Mycobacertium tuberculosis
    Paul R Ortiz de Montellano; Fiscal Year: 2013
    ..tuberculosis. ..
  29. The Role of CYP1B1 in the Recurrence of Head and Neck Cancer
    Ekaterina G Shatalova; Fiscal Year: 2013
    ....
  30. Control of HIV drug resistance in older patients
    Alonso Heredia; Fiscal Year: 2010
    ....
  31. Role of hepatic and pulmonary P4501A enzymes in neonatal hyperoxic tissue injury
    XANTHI IOANNA COUROUCLI; Fiscal Year: 2013
    ....
  32. Novel Mechanisms of Quinone Toxicity
    David Ross; Fiscal Year: 2013
    ..The studies will have broad applicability to a variety of organ systems. ..
  33. 2-Amino-9H-pyrido[2,3-b]indole: a potential colorectal carcinogen formed in tobac
    Robert J Turesky; Fiscal Year: 2013
    ..abstract_text> ..
  34. Mechanisms of Renoprotection by Soluble Epoxide Hydrolase Inhibition
    Deanna L Kroetz; Fiscal Year: 2013
    ..The studies proposed in this application will explore a novel pathway for protection against acute kidney injury which exploits an abundant renal fatty acid epoxide with established roles in inflammation and apoptosis. ..
  35. Role of cytochrome P4501B1 in oxygen-mediated pulmonary injury
    Bhagavatula Moorthy; Fiscal Year: 2013
    ..This project is aimed at developing novel strategies for the prevention/treatment of lung diseases such as BPD and ARDS in humans. ..
  36. Inhibition of Carboxylesterase Metabolism by Ethanol
    Robert B Parker; Fiscal Year: 2011
    ..Understanding this interaction is a necessary component for the safe and effective use of drugs metabolized by carboxylesterases. ! ..
  37. New mechanism and regulation of intracellular heme delivery in mammals
    Dennis J Stuehr; Fiscal Year: 2013
    ..Our findings will touch many aspects of human health and disease, including blood formation, drug response, anemia, and inflammation. ..
  38. Estrogen signaling in portopulmonary hypertension
    Steven M Kawut; Fiscal Year: 2013
    ..Finally, downregulation of CEPs by fulvestrant would identify ERalpha blockade as another approach. If these hypotheses are incorrect, we could use the genetic and biomarker data to examine alternative hypotheses. ..
  39. Role of P450 Eicosanoids in Delayed Microvascular Spasm Following Subarachnoid He
    DOMINIC AARON SILER; Fiscal Year: 2013
    ..Here the aim is to study how disruption of a microvascular vasodilator pathway could cause delayed microvascular spasm after subarachnoid hemorrhage and subsequently, delayed neurological deficit. ..
  40. HEMOPROTEIN OXIDATION AND HEME CATABOLISM
    Paul R Ortiz de Montellano; Fiscal Year: 2013
    ..4. Define the interactions of HO-1 and HO-2 with naturally occurring polymorphic cytochrome P450 reductase (CPR) variants associated with human disease. ..
  41. Cytochrome P4501B1 and basal liver PPARa activity
    COLIN ROBERT JEFCOATE; Fiscal Year: 2013
    ..Serum markers applicable to clinical studies will be used in probing these liver changes. ..
  42. Regulation of Hepatic P450s by Anti-Cholesterol Drugs
    Thomas A Kocarek; Fiscal Year: 2013
    ..Therefore alternative anti-cholesterol drugs are needed. The public health relevance of this project is that it will increase our knowledge about the potential utility of a novel class of anti-cholesterol drugs. ..
  43. Molecular Probes of the Mechanisms of Cytocrhome P450
    JOHN TAYLOR GROVES; Fiscal Year: 2013
    ..abstract_text> ..
  44. Interplay between metabolism and FXR activation in scoparone signaling
    Bingfang Yan; Fiscal Year: 2013
    ..Interestingly, scoparone has been found to exert these very activities. Thus, a confirmation on the functional connection between FXR and scoparone will have broad mechanistic and therapeutic implications. ..
  45. Impact of Pregnancy on Drug Absorption, Disposition and End Organ Response
    Steve N Caritis; Fiscal Year: 2013
    ..Finally, we will evaluate the fetal contribution to the variability in activity of these three CYP enzymes by evaluating cord/placental CYP enzymes/polymorphisms. ..
  46. Antimalarial Pharmacology in HIV Coinfected Children and Pregnant Women in Uganda
    Sunil Parikh; Fiscal Year: 2013
    ..Findings should lead to specific artemether-lumefantrine dosing guidelines based on age, pregnancy, and use with concomitant antiretroviral therapy in HIV-infected populations. ..
  47. EICOSANOIDS AND VASCULAR WALL REMODELING
    Gadiparthi N Rao; Fiscal Year: 2013
    ..Such knowledge would be useful in the development of therapeutic drugs against vascular diseases such as atherosclerosis. ..
  48. Medications Development for the Pregnant Opiate Addict
    Mahmoud S Ahmed; Fiscal Year: 2010
    ..abstract_text> ..
  49. Genetic Susceptibility to PCB-induced Motor Dysfunction
    CHRISTINE PERDAN CURRAN; Fiscal Year: 2012
    ..The proposed research is designed to identify neural pathways affected by PCB exposure and humans at highest risk of PCB developmental neurotoxicity using a mouse model that mirrors known genetic variations in humans. ..
  50. Structure and Function of Integral Membrane Enzyme Human Aromatase
    Debashis Ghosh; Fiscal Year: 2012
    ..Results from this investigation will form the basis for future discovery of novel breast cancer drugs that are highly specific for aromatase but cause minimal side effects. ..
  51. Impact CYP2D6 Phenotype on Response to Methamphetamine in Humans
    Alison Oliveto; Fiscal Year: 2013
    ..Results of this study may uncover genetically determined metabolic factors that may increase or decrease abuse liability of METH, thereby providing new directions for prevention and treatment for METH dependence. ..
  52. Liquid Chromatograph-Triple Quadrupole Mass Spectrometer
    Peyton Jacob; Fiscal Year: 2010
    ..The research projects supported by our resource are developing improved therapies for tobacco addiction, or are investigating exposure to secondhand tobacco smoke in order to reduce its adverse health consequences. ..
  53. Functional studies of PGRMC1 in cholesterol homeostasis
    PETER JOHN ESPENSHADE; Fiscal Year: 2010
    ....
  54. Hepatic drug metabolism in inflammation
    Romi Ghose; Fiscal Year: 2009
    ..Finally, these studies will provide a basis for screening of individualswith polymorphisms in TLR genes during clinical trials of new drugs. ..
  55. TOXICOLOGICAL SIGNIFICANCE OF ALKYLBENZENE METABOLISM
    Wayne L Backes; Fiscal Year: 2013
    ..How the P450s are organized will govern not only their effectiveness in removing foreign compounds from the body, but also their ability to form reactive compounds that can lead to toxicity, cancer, and aging. ..
  56. Exogenous and Endogenous Biomarkers of CYP2D6 Variability in Pediatrics
    YVONNE SARAH LIN; Fiscal Year: 2013
    ..Ultimately, the goal of the research is to personalize the use of medications in children by selecting the appropriate dose of the correct medication for individual patients. ..
  57. The Effect of Genetic Diversity on Mechanism-Based Inactivation of CYP2D6
    Laura L Furge; Fiscal Year: 2013
    ....
  58. Designing HIV Protease Inhibitors with Lower Dosing Requirements and Lower Toxici
    Mitchell W Mutz; Fiscal Year: 2013
    ..By reducing the toxicity of HIV protease inhibitors, we hope to improve compliance with HAART and therapeutic outcomes. ..
  59. Estrogen and EDHF in NO Deficiency
    An Huang; Fiscal Year: 2012
    ..The knowledge generated by these studies will unravel a novel therapeutic target to improve vascular endothelial function by the upregulation of CYP-dependent dilator pathways as an adaptation to NO deficiency. ..
  60. Control of cancer and metastasis by endothelial-derived epoxyeicosatrienoic acids
    Dipak Panigrahy; Fiscal Year: 2013
    ..Conversely, blocking the EET pathway may offer a new strategy to block tumor blood vessels and, hence, help combat cancer. Thus, novel drugs which block EETs will be tested in preclinical trials to confirm their activity. ..
  61. Role of IGF-1R in breast cancer proliferation and survival via CYP1A1 epoxygenase
    MARIANGELLYS RODRIGUEZ; Fiscal Year: 2012
    ..The results will advance the breast cancer field by characterizing the biological mechanism by which the metabolism of dietary omega-3 fatty acids is regulated by insulin-like growth factors to promote the growth of breast cancer. ..
  62. Mechanisms for Benzo(a)pyrene-Induced Colon Cancer Exacerbation by Dietary Fat
    Aramandla Ramesh; Fiscal Year: 2013
    ..Our findings will serve as a prelude to conducting chemoprevention studies for CRC and help to synthesize drugs to prevent or delay the onset of colon cancer. ..
  63. Cellular Efflux and Metabolism of Protease Inhibitors
    Ashim Mitra; Fiscal Year: 2004
    ..The brain parenchymal and alveolar lining - two sanctuary sites that are 'protected' from optimal antiretroviral drug access. 4) to study the effect of protein binding on the influx and efflux of model compounds, and anti-HIV drugs. ..
  64. Garlic Metabolism and Cytochrome P450 Modulation
    Danny Shen; Fiscal Year: 2007
    ..The results will provide critical information for the design of further clinical studies to characterize and elucidate potentially important adverse garlic-drug interactions. [unreadable] [unreadable]..
  65. A BREATH TEST FOR LUNG CANCER
    Michael Phillips; Fiscal Year: 2009
    ..Early, safe and cost-effective detection of lung cancer could potentially reduce the number of lives lost to the disease. ..
  66. CYTOCHROME P450 SUBSTRATE SITING AND MOTION
    Ann McDermott; Fiscal Year: 2002
    ..Studies involving microbial detoxification enzymes with similar chemical mechanisms are also planned. ..
  67. INTESTINAL AND COLONIC CYTOCHROME P450 GENE EXPRESSION
    Peter Traber; Fiscal Year: 1993
    ..And finally, the expression of P450 genes expression along the length of the intestine and as enterocytes mature along the crypt-villus axis...
  68. ANESTHETIC TOXICITY--MECHANISMS AND PREVENTION
    Evan Kharasch; Fiscal Year: 1999
    ..More importantly, potentially bioactivated anesthetics or protoxins may be rationally designed to avoid this metabolic hazard. ..
  69. NADPH P450 REDUCTASE--THYROID HORMONE REGULATION
    David Waxman; Fiscal Year: 2002
    ....
  70. CYTOCHROME P450 DEPENDENT METABOLISM OF DRUGS IN BRAIN
    HENRY STROBEL; Fiscal Year: 2000
    ..This combination of in vitro and in vivo determinations will establish a clear basis for evaluating the potential of brain cytochrome P450 isoforms to metabolize in situ drugs used to treat brain diseases. ..
  71. COMPARISON OF RAT & TROUT HEPATIC P450 INDUCTION
    JOHN LECH; Fiscal Year: 1993
    ....
  72. CYTOCHROME P450 DEPENDENT ARACHIDONIC ACID METABOLISM
    Deanna Kroetz; Fiscal Year: 2004
    ..Application of these principles for regulating CYP eicosanoid formation in other tissues is anticipated. ..
  73. Cytochrome P450-reductase interactions in P450 1A subfamily
    GRAZYNA SZKLARZ; Fiscal Year: 2007
    ..Furthermore, this project will also provide opportunities for summer research by undergraduate students, as part of WV-BRIN and WV-INBRE programs. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  74. CYTOCHROME P450 EICOSANOIDS AND PULMONARY HEMODYNAMICS
    Alan Stephenson; Fiscal Year: 2002
    ..abstract_text> ..
  75. Cytochrome P450 in Reperfusion Injury
    Roberta Gottlieb; Fiscal Year: 2007
    ..This proposal identifies cytochrome P450 monooxygenases as a previously underestimated factor in myocardial reperfusion injury, and establishes the basis for a novel therapeutic approach [unreadable] [unreadable]..
  76. Application of solution NMR to (human) membrane cytochrome P450 17A1
    DAVID FERNANDO ESTRADA; Fiscal Year: 2012
    ....
  77. Relationship Between AD Clinicopathological Changes and CNS Sex Steroid Hormones
    Jeremiah Kelly; Fiscal Year: 2009
    ....