F P Guengerich

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. pmc Minipig cytochrome P450 3A, 2A and 2C enzymes have similar properties to human analogs
    P Soucek
    Group of Biotransformations, Center for Occupational Diseases, National Institute of Public Health, Srobarova 48, Praha 10, 100 42, Czech Republic
    BMC Pharmacol 1:11. 2001
  2. ncbi Forging the links between metabolism and carcinogenesis
    F P Guengerich
    Department of Biochemistry, Center of Molecular Toxicology, Vanderbilt University School of Medicine, 638 Medical Research Building I, 23rd Avenue South at Pierce, Nashville, TN 37232 0146, USA
    Mutat Res 488:195-209. 2001
  3. pmc Involvement of cytochrome P450, glutathione S-transferase, and epoxide hydrolase in the metabolism of aflatoxin B1 and relevance to risk of human liver cancer
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Environ Health Perspect 104:557-62. 1996
  4. ncbi Lack of electron transfer from cytochrome b5 in stimulation of catalytic activities of cytochrome P450 3A4. Characterization of a reconstituted cytochrome P450 3A4/NADPH-cytochrome P450 reductase system and studies with apo-cytochrome b5
    H Yamazaki
    Osaka Prefectural Institute of Public Health, Osaka 537, Japan
    J Biol Chem 271:27438-44. 1996
  5. ncbi Expression of drug-metabolizing enzymes
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Curr Opin Biotechnol 8:623-8. 1997
  6. ncbi Activation of dihaloalkanes by thiol-dependent mechanisms
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    J Biochem Mol Biol 36:20-7. 2003
  7. ncbi Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Chem Biol Interact 106:161-82. 1997
  8. ncbi Activation and detoxication of aflatoxin B1
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mutat Res 402:121-8. 1998
  9. ncbi Activation of procarcinogens by human cytochrome P450 enzymes
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mutat Res 400:201-13. 1998
  10. ncbi What makes P450s work? Searches for answers with known and new P450s
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Drug Metab Rev 32:267-81. 2000

Collaborators

Detail Information

Publications124 found, 100 shown here

  1. pmc Minipig cytochrome P450 3A, 2A and 2C enzymes have similar properties to human analogs
    P Soucek
    Group of Biotransformations, Center for Occupational Diseases, National Institute of Public Health, Srobarova 48, Praha 10, 100 42, Czech Republic
    BMC Pharmacol 1:11. 2001
    ..The purpose of this work is to characterize minipig liver microsomal cytochromes P450 (CYPs) by comparing their N-terminal sequences with corresponding human orthologs...
  2. ncbi Forging the links between metabolism and carcinogenesis
    F P Guengerich
    Department of Biochemistry, Center of Molecular Toxicology, Vanderbilt University School of Medicine, 638 Medical Research Building I, 23rd Avenue South at Pierce, Nashville, TN 37232 0146, USA
    Mutat Res 488:195-209. 2001
    ..Further areas of investigation involve the consequences of enzyme variability in humans and include areas such as genomics, epidemiology, and chemoprevention...
  3. pmc Involvement of cytochrome P450, glutathione S-transferase, and epoxide hydrolase in the metabolism of aflatoxin B1 and relevance to risk of human liver cancer
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Environ Health Perspect 104:557-62. 1996
    ..Some inhibition of microsome-generated genotoxicity was observed with rat epoxide hydrolase; further information on the extent of contribution of this enzyme to AFB1 metabolism is not yet available...
  4. ncbi Lack of electron transfer from cytochrome b5 in stimulation of catalytic activities of cytochrome P450 3A4. Characterization of a reconstituted cytochrome P450 3A4/NADPH-cytochrome P450 reductase system and studies with apo-cytochrome b5
    H Yamazaki
    Osaka Prefectural Institute of Public Health, Osaka 537, Japan
    J Biol Chem 271:27438-44. 1996
    ..We conclude that b5 can facilitate some P450 3A4-catalyzed oxidations by complexing with P450 3A4 and enhancing its reduction by NADPH-P450 reductase, without directly transferring electrons to P450...
  5. ncbi Expression of drug-metabolizing enzymes
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Curr Opin Biotechnol 8:623-8. 1997
    ....
  6. ncbi Activation of dihaloalkanes by thiol-dependent mechanisms
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    J Biochem Mol Biol 36:20-7. 2003
    ..Recently the DNA repair protein O6-alkylguanine transferase has been shown to produce cytotoxicity and genotoxicity by means of a thiol-dependent process with similarities to the glutathione reactions...
  7. ncbi Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Chem Biol Interact 106:161-82. 1997
    ..Some general conclusions are presented about predictability within various P450 subfamilies...
  8. ncbi Activation and detoxication of aflatoxin B1
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mutat Res 402:121-8. 1998
    ..Studies with human hepatocytes indicate a major role for GST M1-1 in AFB1 conjugation and that the model chemoprotective agent oltipraz can act by both inducing GSTs and inhibiting P450s...
  9. ncbi Activation of procarcinogens by human cytochrome P450 enzymes
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mutat Res 400:201-13. 1998
    ..Assignments of roles of particular P450s in the metabolism of chemical carcinogens are discussed, along with the current state of evidence for relationships of particular P450s with human cancer...
  10. ncbi What makes P450s work? Searches for answers with known and new P450s
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Drug Metab Rev 32:267-81. 2000
    ..Current results indicate that this process involves the conversion of endogenous indole to indoxyl by the P450. The reaction may be used in assays of random mutants and has some potential applications in industry...
  11. ncbi Twenty years of biochemistry of human P450s: purification, expression, mechanism, and relevance to drugs
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Drug Metab Dispos 26:1175-8. 1998
    ..These oxidations are not only of fundamental interest in expanding the repertoire of P450 substrates but have significance in light of human exposure to these compounds...
  12. 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...
  13. ncbi Inter-individual differences in the metabolism of environmental toxicants: cytochrome P450 1A2 as a prototype
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Medical Research Building I, 23rd Avenue South at Pierce, Nashville, TN 37232 0146, USA
    Mutat Res 428:115-24. 1999
    ..Some dinitropyrenes are P450 1A2 substrates but others are not. 6-Nitrochrysene can be activated by human P450 1A2 but the (mono) nitropyrenes examined were not; these were oxidized by P450 3A4 instead...
  14. ncbi Formation and reactions of N(7)-aminoguanosine and derivatives
    F P Guengerich
    Departments of Biochemistry and Chemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Chem Res Toxicol 12:906-16. 1999
    ..The results provide an explanation for the numerous products associated with modification of DNA by activated arylamines. However, the contribution of "direct" reaction at the guanine C8 atom cannot be excluded...
  15. ncbi Metabolism of chemical carcinogens
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638B Medical Research Building I, 23rd Avenue South at Pierce, Nashville, Tennessee 37232 146, USA
    Carcinogenesis 21:345-51. 2000
    ..Some of the areas in which future development relevant to carcinogen metabolism is expected involve pathways of transformation of certain chemicals, regulation of genes coding for many of the enzymes under consideration and genomics...
  16. ncbi Use of heterologously-expressed cytochrome P450 and glutathione transferase enzymes in toxicity assays
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, Medical Research Building I, Nashville, TN 37232 0146, USA
    Toxicology 181:261-4. 2002
    ..These systems have been used to compare these GSTs with regard to activation of dihaloalkanes and potential toxicity...
  17. ncbi Cytochrome P450 1B1: a target for inhibition in anticarcinogenesis strategies
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 23rd Pierce Avenue, Nashville, TN 37232 0146, USA
    Mutat Res 523:173-82. 2003
    ..Substituted stilbenes may be useful in preventing cancer caused by estrogens and xenobiotics...
  18. ncbi Reaction of aflatoxin B(1) oxidation products with lysine
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37232 0146, USA
    Chem Res Toxicol 15:780-92. 2002
    ..The binding of AFB(1) dialdehyde to albumin or the protonation of the N6-amino group retards the reaction with Lys residues...
  19. ncbi Reduction of aflatoxin B1 dialdehyde by rat and human aldo-keto reductases
    F P Guengerich
    Departments of Biochemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37232 0146, USA
    Chem Res Toxicol 14:727-37. 2001
    ..3-fold in AFAR activity. Rats treated with AFB1 excreted the dialcohol and a monoalcohol in urine. The results of these studies are consistent with a role of (rat and human) AFAR in protection against AFB1 toxicity...
  20. ncbi N-hydroxyarylamines
    F Peter Guengerich
    Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Drug Metab Rev 34:607-23. 2002
    ..The high mutagenicity of N-hydroxy heterocyclic amines in bacterial systems has provided a useful tool for the development of models useful for screening and chemoprevention and for the generation of P450 enzymes with altered properties...
  21. ncbi Kinetics of ferric cytochrome P450 reduction by NADPH-cytochrome P450 reductase: rapid reduction in the absence of substrate and variations among cytochrome P450 systems
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 36:14741-50. 1997
    ..Overall, the kinetics of ferric P450 reduction cannot be generalized among different P450s in various systems, and concepts regarding influence of substrate, reaction sequence, and a rate-limiting step are not very universal...
  22. ncbi Cytochrome P450 oxidations in the generation of reactive electrophiles: epoxidation and related reactions
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, School of Medicine, Vanderbilt University, 638 Robinson Research Building, 23rd and Pierce Avenues, Nashville, TN 37232 0146, USA
    Arch Biochem Biophys 409:59-71. 2003
    ..Understanding the chemical nature of reactive products is necessary to develop rational strategies for intervention...
  23. ncbi Structure of the aflatoxin B(1) dialdehyde adduct formed from reaction with methylamine
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37232 0146, USA
    Chem Res Toxicol 15:793-8. 2002
    ..P., Arneson, K. O., Williams, K. M., Deng, Z., and Harris, T. M. (2002) Chem. Res. Toxicol. 15, 780-793]...
  24. ncbi Update information on human P450s
    F Peter Guengerich
    Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Drug Metab Rev 34:7-15. 2002
  25. ncbi Cytochrome P450 enzymes in the generation of commercial products
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Nat Rev Drug Discov 1:359-66. 2002
    ..Potential applications range from the use of cytochrome P450s as drug targets, to the use of randomly generated mutants of cytochrome P450s to produce libraries of new chemicals and drugs...
  26. ncbi Uncommon P450-catalyzed reactions
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Curr Drug Metab 2:93-115. 2001
    ....
  27. ncbi Specificity of 17beta-oestradiol and benzo[a]pyrene oxidation by polymorphic human cytochrome P4501B1 variants substituted at residues 48, 119 and 432
    T Shimada
    Osaka Prefectural Institute of Public Health, Japan
    Xenobiotica 31:163-76. 2001
    ....
  28. pmc Expression of mammalian glutathione S-transferase 5-5 in Salmonella typhimurium TA1535 leads to base-pair mutations upon exposure to dihalomethanes
    R Thier
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146
    Proc Natl Acad Sci U S A 90:8576-80. 1993
    ....
  29. ncbi Oxidations of p-alkoxyacylanilides catalyzed by human cytochrome P450 1A2: structure-activity relationships and simulation of rate constants of individual steps in catalysis
    C H Yun
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA
    Biochemistry 40:4521-30. 2001
    ..This analysis of the effects of the individual rate constants provides a framework for consideration of other P450 reactions and rate-limiting steps...
  30. ncbi A new Salmonella typhimurium NM5004 strain expressing rat glutathione S-transferase 5-5: use in detection of genotoxicity of dihaloalkanes using an SOS/umu test system
    Y Oda
    Osaka Prefectural Institute of Public Health, Japan
    Carcinogenesis 17:297-302. 1996
    ..These results indicate that this new tester NM5004 strain expressing a mammalian GST theta class enzyme may be useful for studies of environmental chemicals proposed to be activated or inactivated by GST activity...
  31. ncbi Metabolism of benzo[a]pyrene to trans-7,8-dihydroxy-7, 8-dihydrobenzo[a]pyrene by recombinant human cytochrome P450 1B1 and purified liver epoxide hydrolase
    T Shimada
    Osaka Prefectural Institute of Public Health, 3 69 Nakamichi 1 chome, Higashinari ku, Osaka 537, Japan
    Chem Res Toxicol 12:623-9. 1999
    ....
  32. ncbi Roles of divalent metal ions in oxidations catalyzed by recombinant cytochrome P450 3A4 and replacement of NADPH--cytochrome P450 reductase with other flavoproteins, ferredoxin, and oxygen surrogates
    H Yamazaki
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 34:8380-9. 1995
    ..The reactions could be supported by E. coli cytosol or by purified E. coli flavodoxin and NADPH-flavodoxin reductase. Spinach ferredoxin and NADPH-ferredoxin reductase also supported catalytic activities.(ABSTRACT TRUNCATED AT 250 WORDS)..
  33. ncbi 7-Ethoxycoumarin O-deethylation catalyzed by cytochromes P450 1A2 and 2E1 in human liver microsomes
    H Yamazaki
    Osaka Prefectural Institute of Public Health, Japan
    Biochem Pharmacol 51:313-9. 1996
    ..These results suggest that P450 1A2 is a low Km enzyme for 7-ethoxycoumarin O-deethylation in human liver microsome, although it has a low Vmax value than P450 2E1...
  34. ncbi Inhibition of human cytochrome P450-catalyzed oxidations of xenobiotics and procarcinogens by synthetic organoselenium compounds
    T Shimada
    Osaka Prefectural Institute of Public Health, Japan
    Cancer Res 57:4757-64. 1997
    ..These inhibitory actions may, in part, account for the mechanisms responsible for cancer prevention by organoselenium compounds in laboratory animals...
  35. ncbi Random mutagenesis of human cytochrome p450 2A6 and screening with indole oxidation products
    K Nakamura
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA
    Arch Biochem Biophys 395:25-31. 2001
    ..This approach has potential value in understanding P450 2A6 function and generating new dyestuffs and other products...
  36. ncbi Heterologous expression of cytochrome P450 2D6 mutants, electron transfer, and catalysis of bufuralol hydroxylation: the role of aspartate 301 in structural integrity
    I H Hanna
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Arch Biochem Biophys 393:255-61. 2001
    ....
  37. ncbi Coumarin substrates for cytochrome P450 2D6 fluorescence assays
    K Nakamura
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA
    Anal Biochem 292:280-6. 2001
    ..Several of the compounds are useful as cytochrome P450 2D6 substrates in single-phase, rapid-throughput assays...
  38. ncbi Metabolic activation of heterocyclic amines and other procarcinogens in Salmonella typhimurium umu tester strains expressing human cytochrome P4501A1, 1A2, 1B1, 2C9, 2D6, 2E1, and 3A4 and human NADPH-P450 reductase and bacterial O-acetyltransferase
    Y Oda
    Osaka Prefectural Institute of Public Health, Higashinari ku, 537 0025, Osaka, Japan
    Mutat Res 492:81-90. 2001
    ..beta-Naphthylamine and benzo[a]pyrene did not exhibit genotoxicity in any of the strains. These results suggest that CYP1A2 is the major cytochrome P450 enzyme involved in bioactivation of HCAs...
  39. ncbi Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: mono- and vicinal dihaloethanes
    J B Wheeler
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Chem Res Toxicol 14:1107-17. 2001
    ..Vuilleumier, S., Rose, J. A., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1118-1127], indicative of an inherent difference in the catalytic mechanisms of the bacterial and mammalian GSH transferases...
  40. ncbi Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase
    C Ged
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
    Biochemistry 27:6929-40. 1988
    ....
  41. ncbi Metabolic deactivation of furylfuramide by cytochrome P450 in human and rat liver microsomes
    T Shimada
    Osaka Prefectural Institute of Public Health, Japan
    Carcinogenesis 11:103-10. 1990
    ..The metabolic studies involving HPLC analysis of products followed by spectrophotometric examination have also suggested that furylfuramide can be degraded very rapidly through the aerobic metabolism by liver microsomes...
  42. ncbi Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P450 1B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009
    T Shimada
    Osaka Prefectural Institute of Public Health, 3 69 Nakamichi 1 chome, Higashinari ku, Osaka 537 0025, Japan
    Drug Metab Dispos 29:1176-82. 2001
    ....
  43. ncbi Roles of NADPH-P450 reductase in the O-deethylation of 7-ethoxycoumarin by recombinant human cytochrome P450 1B1 variants in Escherichia coli
    T Shimada
    Osaka Prefectural Institute of Public Health, 3 69 Nakamichi 1 chome, Higashinari ku, Osaka, 537 0025, Japan
    Protein Expr Purif 20:73-80. 2000
    ....
  44. ncbi DNA-glutathione adducts derived from vic-dihaloalkanes: mechanisms of mutagenesis
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146
    Princess Takamatsu Symp 21:101-7. 1990
    ..Physical studies with modified oligonucleotides indicate that the N7-guanyl substitution weakens G-C pairing but does not in itself alter the selectivity of pairing to C in an isolated oligomer...
  45. ncbi Characterization of cytochrome P-450 2B6 in human liver microsomes
    M Mimura
    Osaka Prefectural Institute of Public Health, Japan
    Drug Metab Dispos 21:1048-56. 1993
    ..abstract truncated at 250 words)..
  46. ncbi Expression of modified cytochrome P450 2C10 (2C9) in Escherichia coli, purification, and reconstitution of catalytic activity
    P Sandhu
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146
    Arch Biochem Biophys 306:443-50. 1993
    ..The recombinant P450 2C10 enzymes did not catalyze (S)-mephenytoin 4'-hydroxylation...
  47. ncbi Selectivity of polycyclic inhibitors for human cytochrome P450s 1A1, 1A2, and 1B1
    T Shimada
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Chem Res Toxicol 11:1048-56. 1998
    ....
  48. ncbi Excretion of the mercapturic acid S-[2-(N7-guanyl)ethyl]-N-acetylcysteine in urine following administration of ethylene dibromide to rats
    D H Kim
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
    Cancer Res 49:5843-7. 1989
    ..The measurement of the mercapturic acid may provide a means of noninvasive estimation of DNA adducts derived from EDB exposure...
  49. ncbi Selectivity of rat and human glutathione S-transferases in activation of ethylene dibromide by glutathione conjugation and DNA binding and induction of unscheduled DNA synthesis in human hepatocytes
    J L Cmarik
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
    Cancer Res 50:2747-52. 1990
    ..The results of experiments done in rat and human systems using both purified GST enzymes and intact hepatocytes imply that the genotoxic pathway of EDB metabolism in rats and humans is similar...
  50. ncbi Diversity in mechanisms of substrate oxidation by cytochrome P450 2D6. Lack of an allosteric role of NADPH-cytochrome P450 reductase in catalytic regioselectivity
    I H Hanna
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 23rd and Pierce Avenues, Nashville, TN 37232-0146, USA
    J Biol Chem 276:39553-61. 2001
    ..These differences are the basis for the variable product distributions, not an allosteric influence of the reductase...
  51. ncbi Fluorescence in situ hybridization analysis of chromosomal localization of three human cytochrome P450 2C genes (CYP2C8, 2C9, and 2C10) at 10q24.1
    K Inoue
    Osaka Prefectural Institute of Public Health, Japan
    Jpn J Hum Genet 39:337-43. 1994
    ..The results showed that three human CYP2C8, 2C9, and 2C10 cDNAs were located at the same subchromosomal region, 10q24.1...
  52. ncbi Binding and oxidation of alkyl 4-nitrophenyl ethers by rabbit cytochrome P450 1A2: evidence for two binding sites
    G P Miller
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA
    Biochemistry 40:7262-72. 2001
    ..The agreement between the dissociation constants for the heterogeneous complexes supports the appropriateness of the two binding site model. This novel finding for P450 1A2 may be more common than originally perceived for P450s...
  53. ncbi Expression of modified human cytochrome P450 2E1 in Escherichia coli, purification, and spectral and catalytic properties
    E M Gillam
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146
    Arch Biochem Biophys 312:59-66. 1994
    ..N-Terminal amino acid sequence analysis yielded the expected first 21 residues. The expression system should facilitate the availability of human P450 2E1 and antibodies for studies of the enzyme...
  54. ncbi Identification of retained N-formylmethionine in bacterial recombinant mammalian cytochrome P450 proteins with the N-terminal sequence MALLLAVFL...: roles of residues 3-5 in retention and membrane topology
    M S Dong
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Biochemistry 35:10031-40. 1996
    ..However, the possibility that the differences in N-terminal processing are the result of direct changes in interactions with the deformylase and Met aminopeptidase cannot be excluded...
  55. ncbi Characterization of (+/-)-bufuralol hydroxylation activities in liver microsomes of Japanese and Caucasian subjects genotyped for CYP2D6
    T Shimada
    Osaka Prefectural Institute of Public Health, Japan
    Pharmacogenetics 11:143-56. 2001
    ....
  56. ncbi Roles of different cytochrome P450 enzymes in bioactivation of the potent hepatocarcinogen 3-methoxy-4-aminoazobenzene by rat and human liver microsomes
    H Yamazaki
    Osaka Prefectural Institute of Public Health, Japan
    Carcinogenesis 12:133-9. 1991
    ..From these results it is concluded that multiple P450 enzymes in rat and human liver microsomes are involved in the bioactivation of 3-MeO-AAB, regardless of its selective induction of the rat P450IA2 gene...
  57. pmc Activation of dihaloalkanes by glutathione conjugation and formation of DNA adducts
    F P Guengerich
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232
    Environ Health Perspect 76:15-8. 1987
    ..Glutathione-dependent DNA damage by EDB was also demonstrated in human hepatocyte preparations. The possible relevance of this DNA adduct to genetic damage is discussed...
  58. ncbi Interactions of N7-guanyl methyl- and thioether-substituted d(CATGCCT) derivatives with d(AGGNATG)
    M S Kim
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146
    Chem Res Toxicol 6:900-5. 1993
    ..abstract truncated at 250 words)..
  59. pmc Evidence for cytochrome P-450NF, the nifedipine oxidase, being the principal enzyme involved in the bioactivation of aflatoxins in human liver
    T Shimada
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232
    Proc Natl Acad Sci U S A 86:462-5. 1989
    ..These findings provide a test system for the hypothesis that a specific human disease state (liver cancer) is linked to the level of oxidative metabolism in populations in which aflatoxin ingestion is high...
  60. ncbi Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: mono- and dihalomethanes
    J B Wheeler
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA
    Chem Res Toxicol 14:1118-27. 2001
    ..P. (2001) Chem. Res. Toxicol. 14, 1107-1117]. The halide order appears most important in the dihalomethane conjugation reactions catalyzed by GST 5-5 and less so in GST T1 and DM11, probably due to changes in the rate-limiting steps...
  61. ncbi Characterization of mRNA species related to human liver cytochrome P-450 nifedipine oxidase and the regulation of catalytic activity
    R W Bork
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
    J Biol Chem 264:910-9. 1989
    ..0-kb mRNA species and that a pretranslational control mechanism is primarily involved in the regulation of nifedipine oxidase activity...
  62. ncbi Kinetic analysis of nucleotide incorporation by mammalian DNA polymerase delta
    H J Einolf
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 275:16316-22. 2000
    ..PCNA appears to affect pol delta replication in this model mainly by decreasing the dissociation of the polymerase from the DNA...
  63. ncbi Separation of human liver microsomal tolbutamide hydroxylase and (S)-mephenytoin 4'-hydroxylase cytochrome P-450 enzymes
    P K Srivastava
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146
    Mol Pharmacol 40:69-79. 1991
    ....
  64. ncbi Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity
    F P Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Chem Res Toxicol 14:611-50. 2001
    ..Some of these transformations are involved in the bioactivation and detoxication of xenobiotic chemicals...
  65. ncbi Understanding electron transport systems of Streptomyces cytochrome P450
    Y J Chun
    College of Pharmacy, Chung Ang University, Seoul 156 756, Korea
    Biochem Soc Trans 34:1183-5. 2006
    ..Elucidation of the detailed mechanisms of electron transport system for Streptomyces P450 may provide the perspective for usefulness of P450s as a biocatalyst...
  66. ncbi Purification and characterization of human liver microsomal cytochrome P-450 2A6
    C H Yun
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146
    Mol Pharmacol 40:679-85. 1991
    ..These results emphasize the need to characterize individual P-450 enzymes in order to understand their functions in the context of more complex systems...
  67. ncbi Modification of cytochrome P450 1A2 enzymes by the mechanism-based inactivator 2-ethynylnaphthalene and the photoaffinity label 4-azidobiphenyl
    C H Yun
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
    Biochemistry 31:10556-63. 1992
    ..abstract truncated at 250 words)..
  68. ncbi Xenobiotic-metabolizing cytochromes P450 convert prostaglandin endoperoxide to hydroxyheptadecatrienoic acid and the mutagen, malondialdehyde
    J P Plastaras
    A B Hancock Jr Memorial Laboratory for Cancer Research, Department of Biochemistry, Center in Molecular Toxicology and the Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 275:11784-90. 2000
    ..These results suggest that co-expression of cyclooxygenase-2 and P450s in developing cancers may contribute to genomic instability due to production of the endogenous mutagen, MDA...
  69. ncbi Molecular cloning, expression, and enzymatic characterization of the rat kidney cytochrome P-450 arachidonic acid epoxygenase
    A Karara
    Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232
    J Biol Chem 268:13565-70. 1993
    ....
  70. ncbi Assignment of the human cytochrome P-450 nifedipine oxidase gene (CYP3A4) to chromosome 7 at band q22.1 by fluorescence in situ hybridization
    K Inoue
    Osaka Prefectural Institute of Public Health, Japan
    Jpn J Hum Genet 37:133-8. 1992
    ..We assigned CYP3A4 to chromosome 7 at q22.1...
  71. ncbi Spectroscopic and thermodynamic characterization of the interaction of N7-guanyl thioether derivatives of d(TGCTG*CAAG) with potential complements
    M Persmark
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146
    Biochemistry 33:8662-72. 1994
    ..The possibility that ionization at the guanine N1 position may be involved in mutagenesis by N7-guanyl adducts is considered...
  72. ncbi Fidelity of nucleotide insertion at 8-oxo-7,8-dihydroguanine by mammalian DNA polymerase delta. Steady-state and pre-steady-state kinetic analysis
    H J Einolf
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA
    J Biol Chem 276:3764-71. 2001
    ..pol delta replication fidelity at 8-oxoG depends upon contributions from K(m), K(d)(dNTP), and rates of phosphodiester bond formation, and PCNA is an important accessory protein for incorporation and extension at 8-oxoG adducts...
  73. ncbi Oxidation of phenethylamine derivatives by cytochrome P450 2D6: the issue of substrate protonation in binding and catalysis
    G P Miller
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA
    Biochemistry 40:14215-23. 2001
    ..This result can be explained by the increasing concentration of the inhibitory unprotonated substrate. Nevertheless, the rates of methoxyphenethylamine oxidations are the highest reported for P450 2D6 substrates...
  74. ncbi Formation of the DNA adduct S-[2-(N7-guanyl)ethyl]glutathione from ethylene dibromide: effects of modulation of glutathione and glutathione S-transferase levels and lack of a role for sulfation
    D H Kim
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232
    Carcinogenesis 11:419-24. 1990
    ..These results suggest that induction of the Phase II enzyme GSH S-transferase can be detrimental in the case of ethylene dibromide and that decreases in GSH levels reduce DNA alkylation in rats...
  75. pmc Translesion synthesis across 1,N2-ethenoguanine by human DNA polymerases
    Jeong Yun Choi
    Department of Biochemistry and Chemistry, Vanderbilt University, Nashville, Tennessee 37232 0146, USA
    Chem Res Toxicol 19:879-86. 2006
    ..This pattern differs with the same oligonucleotide sequences and 1,N(2)-epsilon-G observed using Dpo4, emphasizing the importance of pols in mutagenesis events...
  76. ncbi Multiple sequential steps involved in the binding of inhibitors to cytochrome P450 3A4
    Emre M Isin
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 282:6863-74. 2007
    ..We propose a three-step minimal model for inhibitor binding, developed with kinetic simulations, consistent with our previously reported model for the binding of substrates, although it is possible that even more steps are involved...
  77. ncbi Kinetics and thermodynamics of ligand binding by cytochrome P450 3A4
    Emre M Isin
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 281:9127-36. 2006
    ..The P450 3A4 binding process is more complex than a two-state system, and the overlap of rates of some of the events with subsequent steps is proposed to underlie the observed cooperativity...
  78. ncbi Biosynthesis of new indigoid inhibitors of protein kinases using recombinant cytochrome P450 2A6
    Zhongliu Liu Wu
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 23rd and Pierce Avenues, Nashville, Tennessee 37232 0146, USA
    Chem Biodivers 2:51-65. 2005
    ..Thus, this system has the potential to generate new indigoids with therapeutic potential...
  79. pmc Translesion synthesis past the C8- and N2-deoxyguanosine adducts of the dietary mutagen 2-Amino-3-methylimidazo[4,5-f]quinoline in the NarI recognition sequence by prokaryotic DNA polymerases
    James S Stover
    Department of Chemistry, Center in Molecular Toxicology, and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235 1822, USA
    Chem Res Toxicol 19:1506-17. 2006
    ..These results also suggest a possible role for pol II and IV in the error-prone bypass of the C8-IQ-adduct leading to frameshift mutations in reiterated sequences, whereas noniterated sequences result in error-free bypass...
  80. ncbi Inhibition of human cytochrome P450 1A1-, 1A2-, and 1B1-mediated activation of procarcinogens to genotoxic metabolites by polycyclic aromatic hydrocarbons
    Tsutomu Shimada
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 606 Light Hall, 2215 Garland Avenue, Nashville, Tennessee 37232 0146, USA
    Chem Res Toxicol 19:288-94. 2006
    ....
  81. ncbi Kinetic evidence for inefficient and error-prone bypass across bulky N2-guanine DNA adducts by human DNA polymerase iota
    Jeong Yun Choi
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 281:12315-24. 2006
    ..Thus, polymerization by pol iota is severely inhibited by a bulky group at G N2 despite an advantageous mode of Hoogsteen base pairing; pol iota may play a limited role in translesion synthesis on bulky N2-G adducts in cells...
  82. ncbi Translesion synthesis across bulky N2-alkyl guanine DNA adducts by human DNA polymerase kappa
    Jeong Yun Choi
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 281:21062-72. 2006
    ....
  83. ncbi Activation of aminophenylnorharman, aminomethylphenylnorharman and aminophenylharman to genotoxic metabolites by human N-acetyltransferases and cytochrome P450 enzymes expressed in Salmonella typhimurium umu tester strains
    Yoshimitsu Oda
    Osaka Prefectural Institute of Public Health, 3 69 Nanakichi 1 chome, Higashinari ku, Osaka 537 0025, Japan
    Mutagenesis 21:411-6. 2006
    ..From these results, it is concluded that APNH, AMPNH and APH are mainly bioactivated by P450 1A2 and NAT2, followed by NAT1 enzymes. P450 1A1 was also found to activate AMPNH at relatively slower rates...
  84. ncbi Translesion synthesis across O6-alkylguanine DNA adducts by recombinant human DNA polymerases
    Jeong Yun Choi
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 23rd and Pierce Avenues, Nashville, TN 37232 0146, USA
    J Biol Chem 281:38244-56. 2006
    ..The results with pol eta may be relevant to some mutations previously reported with O(6)-alkylG adducts in mammalian cells...
  85. ncbi Effect of alterations of key active site residues in O6-alkylguanine-DNA Alkyltransferase on its ability to modulate the genotoxicity of 1,2-dibromoethane
    Liping Liu
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Chem Res Toxicol 20:155-63. 2007
    ....
  86. ncbi Complex reactions catalyzed by cytochrome P450 enzymes
    Emre M Isin
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 23rd and Pierce Avenues, Nashville, TN 37232 0146, USA
    Biochim Biophys Acta 1770:314-29. 2007
    ..g., aristolochic acid), ring contraction (piperidine nitroxide radical), oxidation of troglitazone, cleavage of amino oxazoles and a 1,2,4-oxadiazole ring, bioactivation of a dihydrobenzoxathiin, and oxidative aryl migration...
  87. pmc Kinetic analysis of translesion synthesis opposite bulky N2- and O6-alkylguanine DNA adducts by human DNA polymerase REV1
    Jeong Yun Choi
    Department of Pharmacology, School of Medicine, Ewha Womans University, 911 1 Mok 6 dong, Yangcheon Gu, Seoul, Republic of Korea
    J Biol Chem 283:23645-55. 2008
    ..We conclude that human REV1, apparently the slowest Y family polymerase, is kinetically highly tolerant to N(2)-adduct at G but not to O(6)-adducts...
  88. doi Cooperativity of cytochrome P450 1A2: interactions of 1,4-phenylene diisocyanide and 1-isopropoxy-4-nitrobenzene
    Emre M Isin
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN 37232 0146, USA
    Arch Biochem Biophys 473:69-75. 2008
    ..Consistent with this view, Ph(NC)2 inhibited the oxidation of 1-isopropoxy-4-nitrobenzene and other substrates...
  89. doi Cooperativity in oxidation reactions catalyzed by cytochrome P450 1A2: highly cooperative pyrene hydroxylation and multiphasic kinetics of ligand binding
    Christal D Sohl
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 283:7293-308. 2008
    ..Elements of this mechanism may be relevant to other cases of P450 cooperativity...
  90. ncbi Reactions of glyceraldehyde 3-phosphate dehydrogenase sulfhydryl groups with bis-electrophiles produce DNA-protein cross-links but not mutations
    Elisabeth M Loecken
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Chem Res Toxicol 21:453-8. 2008
    ....
  91. ncbi Heterologous expression and characterization of wild-type human cytochrome P450 1A2 without conventional N-terminal modification in Escherichia coli
    Dong Hyun Kim
    School of Biological Sciences and Technology and Hormone Research Center, Chonnam National University, 300 Yongbong Dong, Buk Gu, Gwangju 500 757, Republic of Korea
    Protein Expr Purif 57:188-200. 2008
    ..These results reveal that the overall enzymatic properties of wild-type CYP1A2 enzyme are quite similar to those of modified CYP1A2, although its active site environment seems to differ from that of the modified enzyme...
  92. pmc Transcription processing at 1,N2-ethenoguanine by human RNA polymerase II and bacteriophage T7 RNA polymerase
    Alexandra Dimitri
    Department of Biology, New York University, New York, NY 10003, USA
    J Mol Biol 375:353-66. 2008
    ..Thus, our data suggest that this repair pathway is likely engaged in the clearance of the 1,N(2)-epsilon G from actively transcribed DNA...
  93. pmc Structure of the 1,N2-etheno-2'-deoxyguanosine adduct in duplex DNA at pH 8.6
    Ganesh Shanmugam
    Department of Chemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, and the Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37235, USA
    Chem Res Toxicol 20:1601-11. 2007
    ..The 5'-neighbor T(5).A(20) base pair was destabilized with respect to Watson-Crick base pairing. The refined structure predicted a bend in the helical axis associated with the adduct site...
  94. ncbi Analysis of DNA adducts formed in vivo in rats and mice from 1,2-dibromoethane, 1,2-dichloroethane, dibromomethane, and dichloromethane using HPLC/accelerator mass spectrometry and relevance to risk estimates
    Kengo Watanabe
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Chem Res Toxicol 20:1594-600. 2007
    ..The results may be used to address issues in human risk assessment...
  95. ncbi Guanine alkylation by the potent carcinogen aflatoxin B1: quantum chemical calculations
    Urban Bren
    National Institute of Chemistry, Hajdrihova 19, SI 1001 Ljubljana, Slovenia
    Chem Res Toxicol 20:1134-40. 2007
    ..This explains why the planar region of related mycotoxins sterigmatocystin and aflatoxin G 1 could have been evolutionarily optimized in a different way...
  96. pmc Cytochromes P450 catalyze oxidation of alpha,beta-unsaturated aldehydes
    Immaculate Amunom
    Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Arch Biochem Biophys 464:187-96. 2007
    ..P450s are significant participants in metabolism of endogenous and exogenous unsaturated aldehydes in primary rat hepatocytes...
  97. ncbi Electron transport pathway for a Streptomyces cytochrome P450: cytochrome P450 105D5-catalyzed fatty acid hydroxylation in Streptomyces coelicolor A3(2)
    Young Jin Chun
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 282:17486-500. 2007
    ..Thus, an electron transfer pathway to a functional Streptomyces P450 has been established...
  98. ncbi Expansion of substrate specificity of cytochrome P450 2A6 by random and site-directed mutagenesis
    Zhong Liu Wu
    Department of Biochemistry and the Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 280:41090-100. 2005
    ..The N2297Q change is postulated to generate a hydrogen bond between Gln and the substrate oxygen. Thus, the substrate specificity of P450 2A6 was expanded, and new products were obtained in this study...
  99. ncbi Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis
    Donghak Kim
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 280:40319-27. 2005
    ..The attenuation is caused in part to lower binding affinity for NADPH-P450 reductase, but the K476E mutant did not achieve the wild-type coumarin 7-hydroxylation activity even at high reductase concentrations...
  100. ncbi Adduct size limits efficient and error-free bypass across bulky N2-guanine DNA lesions by human DNA polymerase eta
    Jeong Yun Choi
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    J Mol Biol 352:72-90. 2005
    ....
  101. ncbi Decreased coumarin 7-hydroxylase activities and CYP2A6 expression levels in humans caused by genetic polymorphism in CYP2A6 promoter region (CYP2A6*9)
    Kazuma Kiyotani
    Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
    Pharmacogenetics 13:689-95. 2003
    ..Individuals judged as CYP2A6*4/*9 were expected to be poor metabolizers, having extremely low activity of CYP2A6...