{"id":"https://openalex.org/W2086066855","doi":"https://doi.org/10.1021/tx034157r","title":"Analysis of the Kinetic Mechanism of Haloalkane Conjugation by Mammalian \u03b8-Class Glutathione Transferases","display_name":"Analysis of the Kinetic Mechanism of Haloalkane Conjugation by Mammalian \u03b8-Class Glutathione Transferases","publication_year":2003,"publication_date":"2003-10-28","ids":{"openalex":"https://openalex.org/W2086066855","doi":"https://doi.org/10.1021/tx034157r","mag":"2086066855","pmid":"https://pubmed.ncbi.nlm.nih.gov/14615977"},"language":"en","primary_location":{"id":"doi:10.1021/tx034157r","doi":"https://doi.org/10.1021/tx034157r","is_oa":false,"landing_page_url":"https://doi.org/10.1021/tx034157r","pdf_url":null,"source":{"id":"https://openalex.org/S152840809","display_name":"Chemical Research in Toxicology","issn_l":"0893-228X","issn":["0893-228X","1520-5010"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical Research in Toxicology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5058389506","display_name":"Frederick Peter Guengerich","orcid":"https://orcid.org/0000-0002-7458-3048","observed_orcids":["https://orcid.org/0000-0002-7458-3048"]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"F. Peter Guengerich","raw_affiliation_strings":["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","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"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"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","institution_ids":["https://openalex.org/I200719446"]},{"raw_affiliation_string":"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","institution_ids":["https://openalex.org/I200719446"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077735608","display_name":"W. Andrew McCormick","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"W. Andrew McCormick","raw_affiliation_strings":["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"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"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","institution_ids":["https://openalex.org/I200719446"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5030538732","display_name":"James B. Wheeler","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"James B. Wheeler","raw_affiliation_strings":["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"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"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","institution_ids":["https://openalex.org/I200719446"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I200719446"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.4715,"has_fulltext":false,"cited_by_count":29,"citation_normalized_percentile":{"value":0.55546936,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":96},"biblio":{"volume":"16","issue":"11","first_page":"1493","last_page":"1499"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12187","display_name":"Glutathione Transferases and Polymorphisms","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12187","display_name":"Glutathione Transferases and Polymorphisms","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11884","display_name":"Redox biology and oxidative stress","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/glutathione-s-transferase","display_name":"glutathione S-transferase","score":0.9150000214576721},{"id":"https://openalex.org/keywords/dihalomethanes","display_name":"dihalomethanes","score":0.8550000190734863},{"id":"https://openalex.org/keywords/burst-kinetics","display_name":"burst kinetics","score":0.6399999856948853},{"id":"https://openalex.org/keywords/halide-displacement","display_name":"halide displacement","score":0.734000027179718},{"id":"https://openalex.org/keywords/rate-limiting-step","display_name":"rate-determining step","score":0.8600000143051147},{"id":"https://openalex.org/keywords/carbon-halogen-bond-cleavage","display_name":"carbon-halogen bond cleavage","score":0.8309999704360962},{"id":"https://openalex.org/keywords/enzyme-kinetics","display_name":"enzyme kinetics","score":0.5789999961853027},{"id":"https://openalex.org/keywords/chloroethane","display_name":"chloroethane","score":0.6880000233650208},{"id":"https://openalex.org/keywords/dibromomethane","display_name":"dibromomethane","score":0.8410000205039978},{"id":"https://openalex.org/keywords/dichloromethane","display_name":"dichloromethane","score":0.9509999752044678},{"id":"https://openalex.org/keywords/risk-assessment","display_name":"risk assessment","score":0.47099998593330383}],"concepts":[{"id":"https://openalex.org/C538909803","wikidata":"https://www.wikidata.org/wiki/Q116907","display_name":"Glutathione","level":3,"score":0.776005744934082},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6563756465911865},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.6142841577529907},{"id":"https://openalex.org/C3019047270","wikidata":"https://www.wikidata.org/wiki/Q307302","display_name":"Glutathione transferase","level":4,"score":0.5882159471511841},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4682902693748474},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.4376847743988037},{"id":"https://openalex.org/C2777212361","wikidata":"https://www.wikidata.org/wiki/Q5127848","display_name":"Class (philosophy)","level":2,"score":0.4303210377693176},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.3822425603866577},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.33363717794418335},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.24424153566360474},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.10677322745323181},{"id":"https://openalex.org/C138885662","wikidata":"https://www.wikidata.org/wiki/Q5891","display_name":"Philosophy","level":0,"score":0.0},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.0},{"id":"https://openalex.org/C111472728","wikidata":"https://www.wikidata.org/wiki/Q9471","display_name":"Epistemology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000473","descriptor_name":"Alkanes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005025","descriptor_name":"Ethylene Dichlorides","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":false},{"descriptor_ui":"D005025","descriptor_name":"Ethylene Dichlorides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D005978","descriptor_name":"Glutathione","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D005978","descriptor_name":"Glutathione","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D005982","descriptor_name":"Glutathione Transferase","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D005982","descriptor_name":"Glutathione Transferase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006842","descriptor_name":"Hydrocarbons, Brominated","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006846","descriptor_name":"Hydrocarbons, Halogenated","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008697","descriptor_name":"Methane","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D008697","descriptor_name":"Methane","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008697","descriptor_name":"Methane","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D008752","descriptor_name":"Methylene Chloride","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008956","descriptor_name":"Models, Chemical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/tx034157r","doi":"https://doi.org/10.1021/tx034157r","is_oa":false,"landing_page_url":"https://doi.org/10.1021/tx034157r","pdf_url":null,"source":{"id":"https://openalex.org/S152840809","display_name":"Chemical Research in Toxicology","issn_l":"0893-228X","issn":["0893-228X","1520-5010"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical Research in Toxicology","raw_type":"journal-article"},{"id":"pmid:14615977","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/14615977","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical research in toxicology","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G5061398596","display_name":"Center in Molecular Toxicology","funder_award_id":"P30ES000267","funder_id":"https://openalex.org/F4320337361","funder_display_name":"National Institute of Environmental Health Sciences"},{"id":"https://openalex.org/G5554807743","display_name":"ACTIVATION OF PROCARCINOGENS BY GLUTATHIONE CONJUGATION","funder_award_id":"F32CA080376","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G7515229640","display_name":"Bioactivation of Halogenated Hydrocarbons","funder_award_id":"R01ES010546","funder_id":"https://openalex.org/F4320337361","funder_display_name":"National Institute of Environmental Health Sciences"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"},{"id":"https://openalex.org/F4320337361","display_name":"National Institute of Environmental Health Sciences","ror":"https://ror.org/00j4k1h63"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":14,"referenced_works":["https://openalex.org/W1538489656","https://openalex.org/W1581414347","https://openalex.org/W1750764013","https://openalex.org/W1785290851","https://openalex.org/W1806194750","https://openalex.org/W1968417548","https://openalex.org/W1970466480","https://openalex.org/W2001037328","https://openalex.org/W2039139222","https://openalex.org/W2157114285","https://openalex.org/W2168345791","https://openalex.org/W2322901668","https://openalex.org/W2407857062","https://openalex.org/W4211048496"],"related_works":["https://openalex.org/W2063984497","https://openalex.org/W4252031064","https://openalex.org/W1538489656","https://openalex.org/W1838993935","https://openalex.org/W2076639440","https://openalex.org/W1982977939","https://openalex.org/W1583047051","https://openalex.org/W2078979754","https://openalex.org/W1991021104","https://openalex.org/W2418635820"],"abstract_inverted_index":{"Glutathione":[0],"(GSH)":[1],"transferases":[2],"(GSTs)":[3],"catalyze":[4,43],"the":[5,13,19,23,34,37,47,52,57,61,66,114,138,147,159,169,174,184,192,199,203,215,220,226,235,245,247,253,270],"conjugation":[6,115],"of":[7,15,25,33,36,49,51,116,151,171,194,205,209,244,276],"small":[8],"haloalkanes":[9],"with":[10,54,69,83,257],"GSH.":[11],"In":[12],"case":[14],"dihalomethanes":[16],"and":[17,102,106,158,163,177],"vic-1,2-dihaloalkanes,":[18],"reaction":[20,35],"leads":[21],"to":[22,56,79,132,167,179,240],"formation":[24],"genotoxic":[26],"GSH":[27],"conjugates.":[28],"A":[29],"generally":[30],"established":[31],"feature":[32],"mammalian":[38,160,233],"theta-class":[39],"GSTs,":[40,234,246],"which":[41,137,198],"preferentially":[42],"these":[44,122],"reactions,":[45],"is":[46,141,223,238,250,269],"lack":[48],"saturability":[50],"rate":[53,87,204],"regard":[55],"substrate":[58],"concentration.":[59],"However,":[60],"bacterial":[62,155],"GST":[63,100,104,125,156,218],"DM11":[64,75,157],"catalyzes":[65],"same":[67],"reactions":[68,212],"a":[70,84,133,195],"relatively":[71],"low":[72],"K(m).":[73],"Recently,":[74],"has":[76],"been":[77],"shown":[78],"exhibit":[80],"burst":[81,111],"kinetics,":[82],"rate-determining":[85],"k(off)":[86],"for":[88,183,274],"product":[89],"(Stourman":[90],"et":[91],"al.":[92],"(2003)":[93],"Biochemistry":[94],"42,":[95],"11048-11056).":[96],"We":[97],"examined":[98],"rat":[99],"5-5":[101,162],"human":[103],"T1-1":[105,164],"did":[107],"not":[108,178,230],"detect":[109],"any":[110],"kinetics":[112,150],"in":[113,136,146,173,191,197,225,252],"C(2)H(5)Cl,":[117],"CH(2)Br(2),":[118],"or":[119],"CH(2)Cl(2),":[120],"distinguishing":[121],"enzymes":[123],"from":[124],"DM11.":[126],"The":[127,144,186,266],"kinetic":[128],"results":[129,187],"were":[130],"fit":[131],"minimal":[134],"mechanism":[135],"rate-limiting":[139,175],"step":[140],"halide":[142,200,221,248],"displacement.":[143],"differences":[145,172],"steady":[148],"state":[149],"conjugations":[152],"catalyzed":[153,213],"by":[154,214],"GSTs":[161],"are":[165],"concluded":[166],"be":[168,189],"result":[170],"steps":[176],"inherent":[180],"enzyme":[181,254],"affinity":[182],"haloalkanes.":[185],"may":[188],"interpreted":[190],"context":[193],"model":[196],"order":[201,222,249],"affects":[202],"carbon-halogen":[206],"bond":[207],"cleavage":[208,259],"all":[210,243],"such":[211],"GSTs.":[216],"With":[217,232,242],"DM11,":[219],"manifested":[224],"K(m)":[227,237],"parameter":[228,273],"but":[229],"k(cat).":[231],"high":[236],"difficult":[239],"estimate.":[241],"seen":[251],"efficiency,":[255],"k(cat)/K(m),":[256],"C-Br":[258],"approximately":[260],"10-fold":[261],"faster":[262],"than":[263],"C-Cl":[264],"cleavage.":[265],"ratio":[267],"k(cat)/K(m)":[268],"most":[271],"relevant":[272],"issues":[275],"risk":[277],"assessment.":[278]},"counts_by_year":[{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":2},{"year":2019,"cited_by_count":2},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":2},{"year":2016,"cited_by_count":1},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":1},{"year":2012,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}
