Research Topics
Genomes and Genes | J A GoldsteinSummaryAffiliation: National Institutes of Health Country: USA Publications
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Publications
Clinical relevance of genetic polymorphisms in the human CYP2C subfamilyJ A Goldstein
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Br J Clin Pharmacol 52:349-55. 2001..Phenytoin has been reported to cause severe toxicity in PMs. New polymorphisms have been discovered in CYP2C8, which metabolizes taxol (paclitaxel). Genetic testing is available for all of the known CYP2C variant alleles...
A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoinG C Ibeanu
National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA
J Pharmacol Exp Ther 290:635-40. 1999..Restriction fragment length polymerase chain reaction tests were developed to identify the new allelic variants...
An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in CaucasiansG C Ibeanu
NIEHS, Research Triangle Park, NC 27709, USA
Pharmacogenetics 8:129-35. 1998....
Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acidD Dai
Laboratories of Pharmacology and Chemistry and Pulmonary and Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
Pharmacogenetics 11:597-607. 2001..This polymorphism has important clinical and physiological implications in individuals homozygous for this allele...
Identification of human CYP2C19 residues that confer S-mephenytoin 4'-hydroxylation activity to CYP2C9C C Tsao
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Biochemistry 40:1937-44. 2001....
Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2CsT S Klose
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
J Biochem Mol Toxicol 13:289-95. 1999..Although CYP2C8 has been shown to be phenobarbital inducible, neither a barbiturate-responsive regulatory sequence (a Barbie box) nor a phenobarbital-responsive enhancer module (PBREM) was found within the upstream region analyzed...
Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoinG C Ibeanu
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
J Pharmacol Exp Ther 286:1490-5. 1998..Thus, the new CYP2C19*6 allele contributes to the PM phenotype in Caucasians...
Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymesW G Karam
National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Drug Metab Dispos 24:1081-7. 1996..The current work also shows, for the first time, that other CYP2C enzymes (CYP2C8, CYP2C9, and CYP2C18) may contribute to OP hydroxylation at high substrate concentrations. In contrast, OP-S was formed principally by CYP3A4...
Gene structure and upstream regulatory regions of human CYP2C9 and CYP2C18S M de Morais
National Institutes of Environmental Health Sciences, Research Triangle Park, NC 27709
Biochem Biophys Res Commun 194:194-201. 1993..The availability of the sequences of the upstream regions and intron-exon junctions of CYP2C9 and CYP2C18 will allow future analysis of these genes in humans which differ in their ability to metabolize S-mephenytoin and other drugs...
Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humansJ A Goldstein
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Biochemistry 33:1743-52. 1994..These data indicate that 2C19 is the principal determinant of (S)-mephenytoin 4'-hydroxylase activity in human liver...
Identification of residues 99, 220, and 221 of human cytochrome P450 2C19 as key determinants of omeprazole activityG C Ibeanu
NIEHS, National Institute of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 271:12496-501. 1996..Our results thus indicate that amino acids 99, 220, and 221 are key residues that determine the specificity of P450 2C19 for omeprazole...
A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoinR J Ferguson
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
J Pharmacol Exp Ther 284:356-61. 1998..The two cDNAs were also used in an in vitro coupled transcription/translation assay. CYP2C19 protein was translated only from the CYP2C19*1 allele. These data indicate that CYP2C19*4 represents a new PM allele...
Identification and localization of five CYP2Cs in murine extrahepatic tissues and their metabolism of arachidonic acid to regio- and stereoselective productsC C Tsao
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
J Pharmacol Exp Ther 299:39-47. 2001..Our results suggest that the presence of CYP2C enzymes in heart muscle, aorta, kidney, lung, adrenals, eyes, and reproductive organs could regulate important physiological and/or pathological processes in these tissues...
Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in JapaneseS M de Morais
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Mol Pharmacol 46:594-8. 1994..Genetic testing of the families of two Japanese poor metabolizer probands showed that coinheritance of the CYP2C19m1 and CYP2C19m2 alleles was concordant with the autosomal recessive inheritance of the poor metabolizer phenotype...
Characterization of a cDNA for rat P-450g, a highly polymorphic, male-specific cytochrome in the P-450IIC subfamilyP D McClellan-Green
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Biochemistry 28:5832-9. 1989....
Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifosD Dai
National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Pharmacol Exp Ther 299:825-31. 2001..The turnover numbers of the CYP3A4 M445T and P467S alleles to metabolize these compounds were not significantly different from those of wild-type CYP3A4...
Cloning and expression of murine CYP2Cs and their ability to metabolize arachidonic acidG Luo
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences NIEHS, Research Triangle Park, North Carolina 27709, USA
Arch Biochem Biophys 357:45-57. 1998..CYP2C38 and CYP2C40 were found in liver, brain, kidney, and intestine, with trace amounts in lung and heart, while CYP2C37 and CYP2C39 appeared to be liver specific...
Expression of CYP1A1 and CYP1A2 genes in human liverH Schweikl
Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
Pharmacogenetics 3:239-49. 1993..Therefore, sequence changes in the coding region of CYP1A2 did not account for the poor expression of CYP1A2 in this individual...
Biochemistry and molecular biology of the human CYP2C subfamilyJ A Goldstein
National Institutes of Environmental Health Sciences, Research Triangle Park, NC 27709
Pharmacogenetics 4:285-99. 1994..The availability of genotyping tests for this polymorphism will enhance the assessment of the role of this pathway in clinical studies...
Characterization of a cDNA for the unexpressed form of cytochrome P-450g from the (-g) rat and differentiation of its mRNA from that of the (+g) phenotype using specific oligoprobesH N Yeowell
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Biochemistry 29:713-8. 1990..Two specific oligonucleotide probes for (+) P-450g and (-) P-450g containing three base differences between the (+g) and (-g) sequences hybridized differentially to mRNA from the (+g) and (-g) phenotypes.(ABSTRACT TRUNCATED AT 250 WORDS)..
