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 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. ncbi Insect P450 enzymes
    R Feyereisen
    Department of Entomology, University of Arizona, Tucson 85721, USA
    Annu Rev Entomol 44:507-33. 1999
  9. 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
  10. 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

Research Grants

  1. CYTOCHROME P-450 POLYMORPHISM
    Eric Johnson; Fiscal Year: 1993
  2. Influence of Heme on Hepatic Cytochrome P450 Synthesis and Degradation
    Maria Correia; Fiscal Year: 2009
  3. HEPATIC DEGRADATION OF CYTOCHROME P450 ENZYMES
    Maria Almira Correia; Fiscal Year: 2010
  4. Human Cytochrome P450 4F Enzymes and Drug Interactions
    ZHUO MICHAEL WANG; Fiscal Year: 2010
  5. Cellular Efflux and Metabolism of Protease Inhibitors
    Ashim Mitra; Fiscal Year: 2004
  6. TOXICOLOGICAL SIGNIFICANCE OF ALKYLBENZENE METABOLISM
    Wayne Backes; Fiscal Year: 2000
  7. Influence of Heme on Hepatic Cytochrome P450 Synthesis and Degradation
    Maria Almira Correia; Fiscal Year: 2010
  8. Garlic Metabolism and Cytochrome P450 Modulation
    Danny Shen; Fiscal Year: 2007
  9. A BREATH TEST FOR LUNG CANCER
    Michael Phillips; Fiscal Year: 2007
  10. CYTOCHROME P450 SUBSTRATE SITING AND MOTION
    Ann McDermott; Fiscal Year: 2002

Detail Information

Publications269 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 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...
  3. 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...
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. 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...
  9. 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
    ....
  10. 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...
  11. 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
    ....
  12. 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...
  13. 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
    ....
  14. 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...
  15. 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...
  16. 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...
  17. 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
    ....
  18. 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
    ....
  19. 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...
  20. 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
    ....
  21. doi 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...
  22. 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...
  23. 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...
  24. 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
    ....
  25. doi 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...
  26. 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
    ....
  27. 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...
  28. 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...
  29. 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...
  30. 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...
  31. 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...
  32. 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...
  33. 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...
  34. doi 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...
  35. 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...
  36. 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...
  37. 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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
    ....
  42. 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...
  43. 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...
  44. 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...
  45. 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...
  46. 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...
  47. doi 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...
  48. 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...
  49. 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...
  50. doi 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...
  51. 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...
  52. 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...
  53. doi 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...
  54. 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...
  55. 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...
  56. 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...
  57. 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...
  58. ncbi The genetic determinants of the CYP3A5 polymorphism
    E Hustert
    EPIDAUROS Biotechnologie AG, Bernried, Federal Republic of Germany
    Pharmacogenetics 11:773-9. 2001
    ..q = 0.10). In summary, these results should add to efforts to identify clinically relevant, CYP3A5-specific reactions and to further elucidate traits responsible for variable expression of the entire CYP3A family...
  59. ncbi Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development
    Karen Niederreither
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM ULP College de France
    Nat Genet 31:84-8. 2002
    ..We provide genetic evidence that ALDH1A2 and CYP26A1 activities concurrently establish local embryonic retinoic acid levels that must be finely tuned to allow posterior organ development and to prevent spina bifida...
  60. 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...
  61. pmc Substitutions at methionine 220 in the 14alpha-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs
    E Mellado
    Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Carretera Majadahonda Pozuelo Km2, 28220 Madrid, Spain
    Antimicrob Agents Chemother 48:2747-50. 2004
    ..When the mutated cyp51A genes were introduced into an A. fumigatus wild-type strain, the transformants exhibited reduced susceptibility to all triazole agents, confirming that the mutations were responsible for the resistance phenotype...
  62. ncbi Cloning, yeast expression, and characterization of the coupling of two distantly related Arabidopsis thaliana NADPH-cytochrome P450 reductases with P450 CYP73A5
    P Urban
    Centre de Génétique Moléculaire du CNRS, 91198 Gif sur Yvette, France
    J Biol Chem 272:19176-86. 1997
    ..Biochemical characterization of the Arabidopsis ATR1/CYP73A5 and ATR2-1/CYP73A5 systems demonstrates that the two distantly related Arabidopsis reductases similarly support the first oxidative step of the phenylpropanoid general pathway...
  63. ncbi BAS1 and SOB7 act redundantly to modulate Arabidopsis photomorphogenesis via unique brassinosteroid inactivation mechanisms
    Edward M Turk
    Department of Biology, Washington University, Campus Box 1137, One Brookings Drive, St Louis, MO 63130, USA
    Plant J 42:23-34. 2005
    ....
  64. 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...
  65. pmc Mutations in Aspergillus fumigatus resulting in reduced susceptibility to posaconazole appear to be restricted to a single amino acid in the cytochrome P450 14alpha-demethylase
    Paul A Mann
    Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    Antimicrob Agents Chemother 47:577-81. 2003
    ..The transformants exhibited reductions in susceptibility to POS comparable to those exhibited by the original mutants, confirming that point mutations in the cyp51A gene in A. fumigatus can confer reduced susceptibility to POS...
  66. ncbi Overexpression of CYP4G19 associated with a pyrethroid-resistant strain of the German cockroach, Blattella germanica (L.)
    Julia W Pridgeon
    Department of Entomology and Plant Pathology, 301 Funchess Hall, Auburn University, Auburn, AL 36849 5413, USA
    Gene 314:157-63. 2003
    ..e. lower in head+thorax tissues and higher in abdomen tissues) in both the ACY and Apyr-R strains, the overexpression was more evident in the Apyr-R strain in both head+thorax and abdomen tissues than in the ACY strain...
  67. ncbi The use of heterologously expressed drug metabolizing enzymes--state of the art and prospects for the future
    C L Crespi
    GENTEST Corporation, Woburn, MA 01801, USA
    Pharmacol Ther 84:121-31. 1999
    ..Emphasis is given to new applications (screens for CYP inhibition and novel enzyme mixtures) that have been enabled by high level, functional expression of CYP enzymes...
  68. 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...
  69. 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
    ....
  70. ncbi Evidence of significant contribution from CYP3A5 to hepatic drug metabolism
    Weili Huang
    Department of Pharmaceutics, Box 357610, University of Washington, Seattle, WA 98195 7610, USA
    Drug Metab Dispos 32:1434-45. 2004
    ..We suggest that, under conditions when CYP3A5 content represents a significant fraction of the total hepatic CYP3A pool, the contribution of CYP3A5 to the clearance of some drugs may be an important source of interindividual variability...
  71. ncbi The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors
    J M Pascussi
    Institut National de la Santé et de la Recherche Médicale U128, IFR 24, Centre National de la Recherche Scientifique, 1919 Route de Mende, 34293 05, Montpellier, France
    Biochim Biophys Acta 1619:243-53. 2003
    ..Moreover, they influence mutually their relative expression. This review is focused on these different pathways controlling human CYP2B6, CYP2C9 and CYP3A4 gene expression, and the cross-talk between these pathways...
  72. 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...
  73. doi 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...
  74. ncbi Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism
    Yvonne S Lin
    Department of Pharmaceutics, University of Washington, Seattle, Washington 98195, USA
    Mol Pharmacol 62:162-72. 2002
    ..93) as were wt-CYP3A5 and CYP3A4 mRNA (r = 0.76). These findings suggest that CYP3A4 and CYP3A5 genes share a common regulatory pathway for constitutive expression, possibly involving conserved elements in the 5'-flanking region...
  75. 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...
  76. ncbi Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma
    Jian Chen
    Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, No 8 Xishiku St, West District, Beijing, 100034, People s Republic of China
    J Antimicrob Chemother 55:31-7. 2005
    ..To monitor changes in itraconazole susceptibility of isolates from a patient undergoing treatment for pulmonary Aspergillus infection and relate these changes to genotypic/phenotypic alterations...
  77. pmc Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer
    M D Ritchie
    Program in Human Genetics, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232, USA
    Am J Hum Genet 69:138-47. 2001
    ..To our knowledge, this is the first report of a four-locus interaction associated with a common complex multifactorial disease...
  78. ncbi Xenobiotic response in Drosophila melanogaster: sex dependence of P450 and GST gene induction
    Gaelle Le Goff
    Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
    Insect Biochem Mol Biol 36:674-82. 2006
    ..Our study also suggests that xenobiotic-induced changes in P450 levels can affect insect fitness by interfering with hormonally regulated networks...
  79. ncbi Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural ectoderm
    Tetsuhiro Kudoh
    Department of Anatomy and Developmental Biology, University College London, Gower St, London WC1E 6BT, UK
    Development 129:4335-46. 2002
    ..Thus, cyp26 has an important role in linking the Fgf, Wnt and RA signals to regulate AP patterning of the neural ectoderm in the late blastula to gastrula embryo in zebrafish...
  80. pmc Gibberellin modulates anther development in rice via the transcriptional regulation of GAMYB
    Koichiro Aya
    Bioscience and Biotechnology Center, Nagoya University, Nagoya 464 8601, Japan
    Plant Cell 21:1453-72. 2009
    ..Together, these results suggest that GA regulates exine formation and the PCD of tapetal cells and that direct activation of CYP703A3 by GAMYB is key to exine formation...
  81. pmc The cytochrome P450 enzyme CYP96A15 is the midchain alkane hydroxylase responsible for formation of secondary alcohols and ketones in stem cuticular wax of Arabidopsis
    Stephen Greer
    Department of Botany, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z1
    Plant Physiol 145:653-67. 2007
    ....
  82. ncbi Interindividual variability and tissue-specificity in the expression of cytochrome P450 3A mRNA
    Ina Koch
    EPIDAUROS Biotechnologie AG, Bernried, Federal Republic of Germany
    Drug Metab Dispos 30:1108-14. 2002
    ..In summary, these assays and results should aid in our efforts to further dissect the regulation and the physiological and pharmacological significance of CYP3A isozymes...
  83. ncbi The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis
    Daniel W Nebert
    Department of Environmental Health, and Center for Environmental Genetics, University of Cincinnati Medical Center, P O Box 670056, Cincinnati, Ohio 45267 0056, USA
    Nat Rev Cancer 6:947-60. 2006
    ..We suggest a two-tiered system to predict an overall inter-individual risk of tumorigenesis based on DNA variants in certain 'early defence' CYP genes, combined with polymorphisms in various downstream target genes...
  84. ncbi Biodiversity of cytochrome P450 redox systems
    K J McLean
    Department of Biochemistry, University of Leicester, The Henry Wellcome Building, Lancaster Road, Leicester LE1 9HN, UK
    Biochem Soc Trans 33:796-801. 2005
    ..This paper examines some of the recent advances in our understanding of the biodiversity of the P450 redox apparatus, with a particular emphasis on the redox systems in the pathogen Mycobacterium tuberculosis...
  85. pmc A point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus
    T M Diaz-Guerra
    Unidad de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
    Antimicrob Agents Chemother 47:1120-4. 2003
    ..fumigatus wild-type strain (CM-237) was replaced with the mutated cyp51A gene copy of an ITC-resistant strain (AF-72). Two transformants exhibited resistance to ITC, both of which had incorporated the mutated copy of the cyp51A gene...
  86. pmc Two duplicated P450 genes are associated with pyrethroid resistance in Anopheles funestus, a major malaria vector
    Charles S Wondji
    Liverpool School of Tropical Medicine, Liverpool, L3 5QA, United Kingdom
    Genome Res 19:452-9. 2009
    ..This will be a major advance for insecticide resistance management in malaria vectors, which requires the early detection of resistance alleles...
  87. ncbi Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4
    T R Rebbeck
    Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia 19104 6021, USA
    J Natl Cancer Inst 90:1225-9. 1998
    ..The goal of this study was to evaluate the effect of CYP3A4, a gene associated with the oxidative deactivation of testosterone, on the clinical presentation of prostate cancers...
  88. ncbi Genetic susceptibility to adverse drug reactions
    M Pirmohamed
    Department of Pharmacology and Therapeutics, The University of Liverpool, Ashton Street, Liverpool, UK L69 3GE
    Trends Pharmacol Sci 22:298-305. 2001
    ..The overall clinical utility of genotyping in preventing ADRs needs to be proven by the use of prospective randomized controlled clinical trials...
  89. ncbi Jasmonate and salicylate induce expression of herbivore cytochrome P450 genes
    Xianchun Li
    Department of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
    Nature 419:712-5. 2002
    ..This ability to 'eavesdrop' on plant defence signals protects H. zea against toxins produced by host plants...
  90. pmc Retinoic acid regulates sex-specific timing of meiotic initiation in mice
    Jana Koubova
    Howard Hughes Medical Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 103:2474-9. 2006
    ..Because RA signaling regulates Stra8 expression in both embryonic ovaries and adult testes, this portion of the meiotic initiation pathway may be identical in both sexes...
  91. ncbi Disruption of phacA, an Aspergillus nidulans gene encoding a novel cytochrome P450 monooxygenase catalyzing phenylacetate 2-hydroxylation, results in penicillin overproduction
    J M Mingot
    Departamento de Microbiologia Molecular, Centro de Investigaciones Biológicas del Consejo Superior de Investigaciones Científicas, Velazquez 144, Madrid, 28006, Spain
    J Biol Chem 274:14545-50. 1999
    ....
  92. ncbi Regulation of cytochrome p450 by inflammatory mediators: why and how?
    E T Morgan
    Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Drug Metab Dispos 29:207-12. 2001
    ..This review focuses on recent studies on the mechanisms of this down-regulation, as well as the cytokines and cell types involved. Possible reasons for cytochrome P450 down-regulation are discussed...
  93. pmc Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2
    Martin Spiecker
    Department of Medicine II Cardiology, St Josef Hospital, University of Bochum, Gudrunstr 56, 44791 Bochum, Germany
    Circulation 110:2132-6. 2004
    ..The EETs are potent endogenous vasodilators and inhibitors of vascular inflammation. However, it is not known whether genetic polymorphisms of CYP2J2 are associated with increased cardiovascular risks...
  94. ncbi CYP35: xenobiotically induced gene expression in the nematode Caenorhabditis elegans
    Ralph Menzel
    Leibniz Institute of Freshwater Ecology and Inland Fisheries, Muggelseedamm 301, 12587 Berlin, Germany
    Arch Biochem Biophys 438:93-102. 2005
    ..For PCB52, approximately 0.5% of the EC50 induces a 2-fold increase of CYP35 gene expression. Using a double mutant and multiple RNAi of CYP35A/C it was possible to diminish the reproduction decline caused by PCB52 and fluoranthene...
  95. ncbi Inhibition and induction of cytochrome P450 and the clinical implications
    J H Lin
    Merck Research Laboratories, West Point, Pennsylvania, USA
    Clin Pharmacokinet 35:361-90. 1998
    ..Thus, careful evaluation of potential drug interactions of a new drug candidate during the early stage of drug development is essential...
  96. ncbi Insecticide resistance in Anopheles funestus (Diptera: Culicidae) from Mozambique
    S Casimiro
    National Malaria Control Program, National Direction of Health, Av Eduardo Mondlane Salvador Allende, P O Box 264, Maputo, Mozambique
    J Med Entomol 43:267-75. 2006
    ..The high level of metabolically based pyrethroid resistance has implications for current malaria control programs in Mozambique...
  97. ncbi Ligand-based models for the isoform specificity of cytochrome P450 3A4, 2D6, and 2C9 substrates
    Lothar Terfloth
    Computer Chemie Centrum and Institut für Organische Chemie, Universitat Erlangen Nurnberg, Nagelsbachstrasse 25, D 91052, Erlangen, Germany
    J Chem Inf Model 47:1688-701. 2007
    ..For our favored model we showed the strong influence on the predictivity of the way a data set is split into a training and test data set...
  98. pmc Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and Ginkgo biloba
    Bill J Gurley
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    Drugs Aging 22:525-39. 2005
    ....
  99. pmc Daphnia Halloween genes that encode cytochrome P450s mediating the synthesis of the arthropod molting hormone: evolutionary implications
    Kim F Rewitz
    Department of Biology, University of North Carolina, Chapel Hill, NC 27599 3280 USA
    BMC Evol Biol 8:60. 2008
    ..In insects, the CYP enzymes mediating 20E biosynthesis have been identified, but evidence of their probable presence in crustaceans is indirect, relying solely on the ability of crustaceans to synthesize 20E...
  100. pmc Licorice beta-amyrin 11-oxidase, a cytochrome P450 with a key role in the biosynthesis of the triterpene sweetener glycyrrhizin
    Hikaru Seki
    Kihara Institute for Biological Research, Yokohama City University, Maioka cho 641 12, Totsuka ku, Yokohama, Kanagawa 244 0813, Japan
    Proc Natl Acad Sci U S A 105:14204-9. 2008
    ..These results suggest a role for CYP88D6 as a beta-amyrin 11-oxidase in the glycyrrhizin pathway...
  101. ncbi Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms
    Anthony J Lee
    Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina 29208, USA
    Endocrinology 144:3382-98. 2003
    ..In conclusion, many human CYP isoforms are involved in the oxidative metabolism of 17beta-estradiol and estrone, with a varying degree of catalytic activity and distinct regioselectivity...

Research Grants83

  1. CYTOCHROME P-450 POLYMORPHISM
    Eric Johnson; Fiscal Year: 1993
    ..These studies could also identify mutant alleles that contribute to deficiencies of human drug-metabolizing capacity...
  2. Influence of Heme on Hepatic Cytochrome P450 Synthesis and Degradation
    Maria Correia; Fiscal Year: 2009
    ....
  3. HEPATIC DEGRADATION OF CYTOCHROME P450 ENZYMES
    Maria Almira Correia; Fiscal Year: 2010
    ..Together these P450s are responsible for the metabolism of ~65% of clinically relevant drugs, toxins, and carcinogens, with consequently significant potential for drug-drug interactions and toxicity. ..
  4. Human Cytochrome P450 4F Enzymes and Drug Interactions
    ZHUO MICHAEL WANG; Fiscal Year: 2010
    ..This proposal seeks to demonstrate a novel molecular mechanism for the statin-warfarin interaction and provide a pathway to develop an interaction-free statin-warfarin combination. ..
  5. 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. ..
  6. TOXICOLOGICAL SIGNIFICANCE OF ALKYLBENZENE METABOLISM
    Wayne Backes; Fiscal Year: 2000
    ..Furthermore, these studies are expected to provide information helpful in characterizing P450 expression in brain, and correlating the metabolism alkylbenzenes to the CNS effects of these drugs. ..
  7. Influence of Heme on Hepatic Cytochrome P450 Synthesis and Degradation
    Maria Almira Correia; Fiscal Year: 2010
    ....
  8. 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. ..
  9. A BREATH TEST FOR LUNG CANCER
    Michael Phillips; Fiscal Year: 2007
    ..Early, safe and cost-effective detection of lung cancer could potentially reduce the number of lives lost to the disease. ..
  10. CYTOCHROME P450 SUBSTRATE SITING AND MOTION
    Ann McDermott; Fiscal Year: 2002
    ..Studies involving microbial detoxification enzymes with similar chemical mechanisms are also planned. ..
  11. NADPH P450 REDUCTASE--THYROID HORMONE REGULATION
    David Waxman; Fiscal Year: 2002
    ....
  12. TOXICOLOGICAL ASPECTS OF HEMOPROTEIN REGULATION
    Yoichi Osawa; Fiscal Year: 2000
    ..Conversely, the same knowledge could be used to design more effective inhibitors of NOS for pharmacological use in a variety of neurological diseases. ..
  13. Exogenous and Endogenous Biomarkers of CYP2D6 Variability in Pediatrics
    YVONNE SARAH LIN; Fiscal Year: 2010
    ..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. ..
  14. 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. ..
  15. 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. ..
  16. CYTOCHROME P450 EICOSANOIDS AND PULMONARY HEMODYNAMICS
    Alan Stephenson; Fiscal Year: 2002
    ..abstract_text> ..
  17. 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 ..
  18. Drug-Mediated Alteration of Cytochrome P450
    Yoichi Osawa; Fiscal Year: 2010
    ..The discoveries made through this line of study indicate that a new way to target proteins for degradation may have important therapeutic uses. ..
  19. Predicting Rates and Regioselectivity in Cytochrome P450 Mediated Reactions
    Jeffrey Jones; Fiscal Year: 2009
    ..This grant application will develop methods to design new drugs faster, and safer than we can presently through an increased understanding of the rates and binding affinities or P450 mediated reactions. ..