@article{usmani_rose_goldstein_taylor_brimfield_hodgson_2002, title={In vitro human metabolism and interactions of repellent N,N-diethyl-M-toluamide}, volume={30}, ISSN={["1521-009X"]}, DOI={10.1124/dmd.30.3.289}, abstractNote={Oxidative metabolism of the insect repellent N,N-diethyl-m-toluamide (DEET) by pooled human liver microsomes (HLM), rat liver microsomes (RLM), and mouse liver microsomes (MLM) was investigated. DEET is metabolized by cytochromes P450 (P450s) leading to the production of a ring methyl oxidation product, N,N-diethyl-m-hydroxymethylbenzamide (BALC), and an N-deethylated product, N-ethyl-m-toluamide (ET). Both the affinities and intrinsic clearance of HLM for ring hydroxylation are greater than those for N-deethylation. Pooled HLM show significantly lower affinities (K(m)) than RLM for metabolism of DEET to either of the primary metabolites (BALC and ET). Among 15 cDNA-expressed P450 enzymes examined, CYP1A2, 2B6, 2D6*1 (Val(374)), and 2E1 metabolized DEET to the BALC metabolite, whereas CYP3A4, 3A5, 2A6, and 2C19 produced the ET metabolite. CYP2B6 is the principal cytochrome P450 involved in the metabolism of DEET to its major BALC metabolite, whereas CYP2C19 had the greatest activity for the formation of the ET metabolite. Use of phenotyped HLMs demonstrated that individuals with high levels of CYP2B6, 3A4, 2C19, and 2A6 have the greatest potential to metabolize DEET. Mice treated with DEET demonstrated induced levels of the CYP2B family, increased hydroxylation, and a 2.4-fold increase in the metabolism of chlorpyrifos to chlorpyrifos-oxon, a potent anticholinesterase. Preincubation of human CYP2B6 with chlorpyrifos completely inhibited the metabolism of DEET. Preincubation of human or rodent microsomes with chlorpyrifos, permethrin, and pyridostigmine bromide alone or in combination can lead to either stimulation or inhibition of DEET metabolism.}, number={3}, journal={DRUG METABOLISM AND DISPOSITION}, author={Usmani, KA and Rose, RL and Goldstein, JA and Taylor, WG and Brimfield, AA and Hodgson, E}, year={2002}, month={Mar}, pages={289–294} }
 @article{dai_tang_rose_hodgson_bienstock_mohrenweiser_goldstein_2001, title={Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos}, volume={299}, number={3}, journal={Journal of Pharmacology and Experimental Therapeutics}, author={Dai, D. and Tang, J. and Rose, R. and Hodgson, E. and Bienstock, R. J. and Mohrenweiser, H. W. and Goldstein, J. A.}, year={2001}, pages={825–831} }
 @article{lankford_bai_goldstein_2000, title={Cloning of canine cytochrome P450 2E1 CDNA: identification and characterization of two variant alleles}, volume={28}, number={8}, journal={Drug Metabolism and Disposition}, author={Lankford, S. M. and Bai, S. A. and Goldstein, J. A.}, year={2000}, pages={981–986} }
 @article{klose_blaisdell_goldstein_1999, title={Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs}, volume={13}, ISSN={["1095-6670"]}, DOI={10.1002/(SICI)1099-0461(1999)13:6<289::AID-JBT1>3.0.CO;2-N}, abstractNote={Extrahepatic tissue distribution of the mRNAs for the four human CYP2Cs (2C8, 2C9, 2C18, and 2C19) was examined in kidney, testes, adrenal gland, prostate, brain, uterus, mammary gland, ovary, lung, and duodenum. CYP2C mRNAs were detected by RT‐PCR using specific primers for each individual CYP2C. CYP2C8 mRNA was detected in the kidney, adrenal gland, brain, uterus, mammary gland, ovary, and duodenum. CYP2C9 mRNA was detected in the kidney, testes, adrenal gland, prostate, ovary, and duodenum. CYP2C18 mRNA was found only in the brain, uterus, mammary gland, kidney, and duodenum and CYP2C19 mRNA was found only in the duodenum. Immunoblot analysis of small intestinal microsomes detected both 2C9 and 2C19 proteins. In addition, genomic clones for CYP2C8 were sequenced, and long‐distance PCR was performed to determine the complete gene structure. CYP2C8 spanned a 31 kb region. Comparative analysis of the 2.4 kb upstream region of CYP2C8 with CYP2C9 revealed two previously unidentified transcription factors sites, C/EBP and HPF‐1, and the latter might be involved in hepatic expression. 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. © 1999 John Wiley & Sons, Inc. J Biochem Toxicol 13: 289–295, 1999}, number={6}, journal={JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY}, author={Klose, TS and Blaisdell, JA and Goldstein, JA}, year={1999}, pages={289–295} }
 @article{shetty_hough-goldstein_1998, title={Behavioral response of Podisus maculiventris (Hemiptera : Pentatomidae) to its synthetic pheromone}, volume={33}, ISSN={["0749-8004"]}, DOI={10.18474/0749-8004-33.1.72}, abstractNote={A wind-tunnel bioassay was used to determine the effect of age and feeding history (starvation) on the response of Podisus maculiventris (Say) to its synthetic pheromone. Starved male and female adults showed positive anemotaxis toward the pheromone source; well-fed insects did not. This supports the hypothesis that P. maculiventris adults use the pheromone as a cue indicating presence of prey, in addition to a mating cue, although a physiological explanation for the lack of response by well-fed insects is also possible. In the presence of the pheromone, fed as well as starved insects increased activities such as extending antennae upwind; fluttering wings; and rubbing antennae, proboscis, forelegs, hindlegs, and abdomen. These activities may indicate stimulation of olfactory receptors on antennae and contact chemoreceptors elsewhere on the body. First- to third-generation offspring of field-collected P. maculiventris showed greater response to the synthetic pheromone compared with individuals from a 2-year-old laboratory colony, indicating the importance of using field-collected insects in behavioral studies. Fifth instars did not respond to the synthetic pheromone in the wind tunnel.}, number={1}, journal={JOURNAL OF ENTOMOLOGICAL SCIENCE}, author={Shetty, PN and Hough-Goldstein, JA}, year={1998}, month={Jan}, pages={72–81} }
 @article{luo_zeldin_blaisdell_hodgson_goldstein_1998, title={Cloning and expression of murine CYP2Cs and their ability to metabolize arachidonic acid}, volume={357}, ISSN={["1096-0384"]}, DOI={10.1006/abbi.1998.0806}, abstractNote={Five murine cytochrome P450 (CYP) 2C cDNAs were cloned and characterized, including four new members of this subfamily: CYP2C37, CYP2C38, CYP2C39, and CYP2C40. The cDNAs ranged from 1716 to 1812 bp in length and encoded polypeptides of 490 amino acid residues except for CYP2C40, which contained an additional glutamic acid residue at the carboxyl terminus. The amino acid identity of the murine CYP2Cs ranged from 69 to 92%, while the overall amino acid identity was 60%; however, within the six putative substrate recognition sites the identity was only 25 to 41%, suggesting possible differences in substrate specificity and product profiles. The CYP2C cDNAs were expressed in Escherichia coli following modification of the N-terminus. All five recombinant CYP2Cs metabolized arachidonic acid, but with different metabolic profiles and catalytic rates. Based on coelution with authentic standards on reverse-phase HPLC, themajor metabolites were tentatively identified asfollows: CYP2C29 and CYP2C39 produced 14, 15-cis-epoxyeicosatrienoic acid (EET); CYP2C37 produced 12-hydroxyeicosatetraenoic acid (HETE); CYP2C38 produced 11,12-EET; and CYP2C40 produced an unidentified metabolite that coeluted with 16-,17-, and 18-HETEs. The turnover numbers for CYP2C29, CYP2C37, CYP2C38, CYP2C39, and CYP2C40 were 0.34, 1.12, 5.15, 0.51, and 0.15 nmol/nmol/min, respectively. Reverse transcriptase-polymerase chain reaction demonstrated the presence of CYP2C29 mRNA in liver as well as in extrahepatic tissues including brain, kidney, lung, heart, and intestine. 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.}, number={1}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Luo, G and Zeldin, DC and Blaisdell, JA and Hodgson, E and Goldstein, JA}, year={1998}, month={Sep}, pages={45–57} }
 @article{klose_ibeanu_ghanayem_pedersen_li_hall_goldstein_1998, title={Identification of residues 286 and 289 as critical for conferring substrate specificity of human CYP2C9 for diclofenac and ibuprofen}, volume={357}, ISSN={["0003-9861"]}, DOI={10.1006/abbi.1998.0826}, abstractNote={Specificity of human CYP2C9 for two substrates, diclofenac and ibuprofen, was studied using chimeras and site-directed mutants of CYP2C9 and the highly related CYP2C19 expressed in Escherichia coli. Data were correlated with the presence of putative substrate recognition sites (SRS). A CYP2C19 chimera containing residues 228-340 (SRS 3 and 4) of 2C9 conferred both diclofenac hydroxylation and 2- and 3-hydroxylation of ibuprofen. The regiospecificity of this construct for metabolism of ibuprofen differed from that of CYP2C9 by favoring 2-hydroxylation over 3-hydroxylation. A CYP2C9 construct containing residues 228-340 of CYP2C19 lacked both diclofenac and ibuprofen hydroxylase activities. When residues 228-282 (containing SRS 3) of CYP2C9 were replaced by those of CYP2C19, the chimera retained appreciable activity for diclofenac and ibuprofen, and tolbutamide activity was inhibited by a specific CYP2C9 inhibitor, sulfaphenazole. This suggested that SRS 3 is not important in conferring specificity. CYP2C9 and CYP2C19 differ in five residues within the region 283-340 (within SRS 4). Mutations to analyze SRS 4 were made on a CYP2C19 chimera containing residues 228-282 of CYP2C9. A single I289N mutation conferred a dramatic increase in diclofenac hydroxylation and a small increase in ibuprofen 2-hydroxylation. A second mutation (N286S and I289N) increased diclofenac hydroxylation and conferred a dramatic increase in ibuprofen 2-hydroxylation. A V288E mutation did not increase activity toward either substrate and decreased activity toward the two substrates in combination with the I289N or the N286S, I289N mutants. Therefore residues 286 and 289 of CYP2C9 are important in conferring specificity for diclofenac and ibuprofen.}, number={2}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Klose, TS and Ibeanu, GC and Ghanayem, BI and Pedersen, LG and Li, LP and Hall, SD and Goldstein, JA}, year={1998}, month={Sep}, pages={240–248} }
 @article{blaisdell_goldstein_bai_1998, title={Isolation of a new canine cytochrome P450 cDNA from the cytochrome P450 2C subfamily (CYP2C41) and evidence for polymorphic differences in its expression}, volume={26}, number={3}, journal={Drug Metabolism and Disposition}, author={Blaisdell, J. and Goldstein, J. A. and Bai, S. A.}, year={1998}, pages={278–283} }
 @article{sullivanklose_ghanayem_bell_zhang_kaminsky_shenfield_miners_birkett_goldstein_1996, title={The role of the CYP2C9-Leu(359) allelic variant in the tolbutamide polymorphism}, volume={6}, ISSN={["0960-314X"]}, DOI={10.1097/00008571-199608000-00007}, abstractNote={Tolbutamide undergoes hydroxylation in humans via a cytochrome P450-mediated pathway. The primary P450 isozyme responsible for this metabolism is thought to be CYP2C9. Population studies have indicated the existence of slow metabolizers of tolbutamide (approximately 1 in 500) suggesting a rare polymorphism associated with 2C9. Several allelic variants of 2C9 have been identified; however, the effect of these allelic variations on metabolism in vivo is not established. In the present study, the coding regions, intron-exon junctions, and upstream region of CYP2C9 were amplified by PCR and sequenced in two slow metabolizers. One individual was homozygous for Leu359/Leu359 and the other individual was heterozygous for Arg144/Cys144 and for Ile359/Leu359. No other genetic variations in 2C9 were detected in these individuals. PCR-RFLP tests showed that Arg144 Tyr358 Ile359 Gly417 is the principle CYP2C9 allele. Frequencies of the rarer Leu359 and Cys144 alleles were 0.06 and 0.08, respectively, in a Caucasian-American population and 0.005 and 0.01 respectively in African-Americans. The frequency of the Leu359 allele was 0.026 in Chinese-Taiwanese, but the Cys144 allele was not detected in this population. Studies in a recombinant yeast expression system showed that the Leu359 variant had the highest Km and the lowest Vmac for hydroxylation of tolbutamide of all the CYP2C9 allelic variants. This allelic variant also had the highest Km for the 7-hydroxylation of S-warfarin. The present data suggest that the incidence of the Leu359 allelic variant of CYP2C9 may account for the occurrence of poor metabolizers of tolbutamide.}, number={4}, journal={PHARMACOGENETICS}, author={SullivanKlose, TH and Ghanayem, BI and Bell, DA and Zhang, ZY and Kaminsky, LS and Shenfield, GM and Miners, JO and Birkett, DJ and Goldstein, JA}, year={1996}, month={Aug}, pages={341–349} }