;PMID: 6150824 ;source_file_1017.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..44] = [t:0..44] ;1)sentence:[e:50..123] = [t:50..123] ;2)sentence:[e:125..185] = [t:125..185] ;3)section:[e:189..252] = [t:189..252] ;4)sentence:[e:256..486] = [t:256..486] ;5)sentence:[e:487..631] = [t:487..631] ;6)sentence:[e:632..708] = [t:632..708] ;7)sentence:[e:709..1000] = [t:709..1000] ;8)sentence:[e:1001..1309] = [t:1001..1309] ;9)section:[e:1313..1357] = [t:1313..1357] ;section 0 Span:0..44 ;Drug Metab Dispos. 1984 Nov-Dec;12(6):742-8. (SEC (FRAG (NNP:[0..4] Drug) (NNP:[5..10] Metab) (NNP:[11..17] Dispos) (.:[17..18] .) (CD:[19..23] 1984) (::[24..28] Nov-) (CD:[28..35] Dec;12-LRB-) (CD:[35..37] 6-RRB-) (CD:[37..41] :742) (::[41..42] -) (CD:[42..44] 8.))) ;sentence 1 Span:50..123 ;In vitro metabolism of mono-2-ethylhexyl phthalate by microsomal enzymes. ;[73..100]:substance:"mono-2-ethylhexyl phthalate" ;[115..122]:substance:"enzymes" (SENT (NP-HLN (NP (ADJP (FW:[50..52] In) (FW:[53..58] vitro)) (NN:[59..69] metabolism)) (PP (IN:[70..72] of) (NP (NN:[73..90] mono-2-ethylhexyl) (NN:[91..100] phthalate))) (PP (IN:[101..103] by) (NP (JJ:[104..114] microsomal) (NNS:[115..122] enzymes))) (.:[122..123] .))) ;sentence 2 Span:125..185 ;Similarity to omega- and (omega-1) oxidation of fatty acids. ;[173..184]:substance:"fatty acids" (SENT (NP (NP (NN:[125..135] Similarity)) (PP (TO:[136..138] to) (NP (NP (NP (SYM:[139..144] omega) (HYPH:[144..145] -) (NML-1 (-NONE-:[145..145] *P*))) (CC:[146..149] and) (NP (-LRB-:[150..151] -LRB-) (NML (SYM:[151..156] omega) (HYPH:[156..157] -) (CD:[157..158] 1)) (-RRB-:[158..159] -RRB-) (NML-1 (NN:[160..169] oxidation)))) (PP (IN:[170..172] of) (NP (JJ:[173..178] fatty) (NNS:[179..184] acids))))) (.:[184..185] .))) ;section 3 Span:189..252 ;Albro PW, Chae K, Philpot R, Corbett JT, Schroeder J, Jordan S. (SEC (FRAG (NNP:[189..194] Albro) (NNP:[195..197] PW) (,:[197..198] ,) (NNP:[199..203] Chae) (NNP:[204..205] K) (,:[205..206] ,) (NNP:[207..214] Philpot) (NNP:[215..217] R,) (NNP:[218..225] Corbett) (NNP:[226..228] JT) (,:[228..229] ,) (NNP:[230..239] Schroeder) (NNP:[240..242] J,) (NNP:[243..249] Jordan) (NNP:[250..252] S.))) ;sentence 4 Span:256..486 ;Mono-2-ethylhexyl pthalate (MEHP) is oxidized to omega-, omega-1-, and ;omega-2-hydroxylation products as well as (very slightly) to a dicarboxylic ;acid by washed microsomes from rat liver and kidney, and rabbit but not rat ;lung. ;[256..282]:substance:"Mono-2-ethylhexyl pthalate" ;[284..288]:substance:"MEHP" ;[391..408]:substance:"dicarboxylic acid" (SENT (S (NP-SBJ-4 (NP (NN:[256..273] Mono-2-ethylhexyl) (NN:[274..282] pthalate)) (NP (-LRB-:[283..284] -LRB-) (NN:[284..288] MEHP) (-RRB-:[288..289] -RRB-))) (VP (VBZ:[290..292] is) (VP (VP (VBN:[293..301] oxidized) (NP-4 (-NONE-:[301..301] *)) (PP (PP (TO:[302..304] to) (NP (NP (SYM:[305..310] omega) (HYPH:[310..311] -) (NML-3 (-NONE-:[311..311] *P*))) (,:[311..312] ,) (NP (NML (SYM:[313..318] omega) (HYPH:[318..319] -) (CD:[319..320] 1)) (HYPH:[320..321] -) (NML-3 (-NONE-:[321..321] *P*))) (,:[321..322] ,) (CC:[323..326] and) (NP (NML (SYM:[328..333] omega) (HYPH:[333..334] -) (CD:[334..335] 2)) (HYPH:[335..336] -) (NML-3 (NN:[336..349] hydroxylation) (NNS:[350..358] products))))) (CONJP (RB:[359..361] as) (RB:[362..366] well) (IN:[367..369] as)) (PP (PRN (-LRB-:[370..371] -LRB-) (ADVP (RB:[371..375] very) (RB:[376..384] slightly)) (-RRB-:[384..385] -RRB-)) (TO:[386..388] to) (NP (DT:[389..390] a) (JJ:[391..403] dicarboxylic) (NN:[404..408] acid)))) (PP (IN:[410..412] by) (NP (NP-LGS (VBN:[413..419] washed) (NNS:[420..430] microsomes)) (PP (IN:[431..435] from) (NP=5 (NP (NP (NML-2 (NN:[436..439] rat)) (NN:[440..445] liver)) (CC:[446..449] and) (NP (NML-2 (-NONE-:[449..449] *P*)) (NN:[450..456] kidney))) (,:[456..457] ,) (CC:[458..461] and) (NP (NN:[462..468] rabbit) (NML-1 (-NONE-:[468..468] *P*)))))))) (CC:[469..472] but) (VP (RB:[473..476] not) (NP=5 (NN:[477..480] rat) (NML-1 (NN:[481..485] lung)))))) (.:[485..486] .))) ;sentence 5 Span:487..631 ;The reactions involve molecular oxygen, are strongly inhibited by carbon ;monoxide and oxidized cytochrome c, and NADPH is preferred over NADH. ;[520..526]:substance:"oxygen" ;[554..569]:substance:"carbon monoxide" ;[584..596]:substance:"cytochrome c" ;[602..607]:substance:"NADPH" ;[626..630]:substance:"NADH" (SENT (S (S (NP-SBJ-2 (DT:[487..490] The) (NNS:[492..501] reactions)) (VP (VP (VBP:[502..509] involve) (NP (JJ:[510..519] molecular) (NN:[520..526] oxygen))) (,:[526..527] ,) (VP (VBP:[528..531] are) (ADVP (RB:[532..540] strongly)) (VP (VBN:[541..550] inhibited) (NP-2 (-NONE-:[550..550] *)) (PP (IN:[551..553] by) (NP-LGS (NP (NN:[554..560] carbon) (NN:[561..569] monoxide)) (CC:[571..574] and) (NP (VBN:[575..583] oxidized) (NN:[584..594] cytochrome) (NN:[595..596] c)))))))) (,:[596..597] ,) (CC:[598..601] and) (S (NP-SBJ-1 (NN:[602..607] NADPH)) (VP (VBZ:[608..610] is) (VP (VBN:[611..620] preferred) (NP-1 (-NONE-:[620..620] *)) (PP (IN:[621..625] over) (NP (NN:[626..630] NADH)))))) (.:[630..631] .))) ;sentence 6 Span:632..708 ;Piperonyl butoxide inhibits hydroxylation of MEHP, but clofibrate does not. ;[632..650]:substance:"Piperonyl butoxide" ;[678..682]:substance:"MEHP" ;[688..698]:substance:"clofibrate" (SENT (S (S (NP-SBJ (NN:[632..641] Piperonyl) (NN:[642..650] butoxide)) (VP (VBZ:[652..660] inhibits) (NP (NP (NN:[661..674] hydroxylation)) (PP (IN:[675..677] of) (NP (NN:[678..682] MEHP)))))) (,:[682..683] ,) (CC:[684..687] but) (S (NP-SBJ (NN:[688..698] clofibrate)) (VP (VBZ:[699..703] does) (RB:[704..707] not) (VP (-NONE-:[707..707] *?*)))) (.:[707..708] .))) ;sentence 7 Span:709..1000 ;The differential effects of inducers (phenobarbital and clofibrate) and ;inhibitors (sodium laurate, n-decane, metyrapone) on terminal and ;subterminal hydroxylation as well as differences in apparent Km for the two ;suggest that rat liver contains at least two different MEHP hydroxylases. ;[738..746]:substance:"inducers" ;[748..761]:substance:"phenobarbital" ;[766..776]:substance:"clofibrate" ;[782..792]:substance:"inhibitors" ;[794..809]:substance:"sodium laurate" ;[811..819]:substance:"n-decane" ;[821..831]:substance:"metyrapone" ;[911..913]:quantitative-name:"Km" ;[982..999]:substance:"MEHP hydroxylases" (SENT (S (NP-SBJ (NP (NP (DT:[709..712] The) (JJ:[713..725] differential) (NNS:[727..734] effects)) (PP (IN:[735..737] of) (NP (NP (NNS:[738..746] inducers) (PRN (-LRB-:[747..748] -LRB-) (NP (NN:[748..761] phenobarbital) (CC:[762..765] and) (NN:[766..776] clofibrate)) (-RRB-:[776..777] -RRB-))) (CC:[778..781] and) (NP (NNS:[782..792] inhibitors) (PRN (-LRB-:[793..794] -LRB-) (NP (NP (NN:[794..800] sodium) (NN:[802..809] laurate)) (,:[809..810] ,) (NP (NN:[811..819] n-decane)) (,:[819..820] ,) (NP (NN:[821..831] metyrapone))) (-RRB-:[831..832] -RRB-))))) (PP (IN:[833..835] on) (NP (NP (JJ:[836..844] terminal) (NML-1 (-NONE-:[844..844] *P*))) (CC:[845..848] and) (NP (JJ:[849..860] subterminal) (NML-1 (NN:[861..874] hydroxylation)))))) (CONJP (RB:[875..877] as) (RB:[878..882] well) (IN:[884..886] as)) (NP (NP (NNS:[887..898] differences)) (PP (IN:[899..901] in) (NP (NP (JJ:[902..910] apparent) (NN:[911..913] Km)) (PP (IN:[914..917] for) (NP (DT:[918..921] the) (CD:[922..925] two))))))) (VP (VBP:[926..933] suggest) (SBAR (IN:[934..938] that) (S (NP-SBJ (NN:[939..942] rat) (NN:[943..948] liver)) (VP (VBZ:[949..957] contains) (NP (QP (IN:[958..960] at) (JJS:[962..967] least) (CD:[968..971] two)) (JJ:[972..981] different) (NN:[982..986] MEHP) (NNS:[987..999] hydroxylases)))))) (.:[999..1000] .))) ;sentence 8 Span:1001..1309 ;Comparisons of tissue distribution, susceptibility to inhibitors, and ;induction properties suggest that the hydroxylation of MEHP is more likely ;to be mediated by the P-450 isozymes associated with omega- and ;(omega-1)-hydroxylation of fatty acids than with those that utilize ;hydrocarbons as substrates. ;[1056..1066]:substance:"inhibitors" ;[1128..1132]:substance:"MEHP" ;[1170..1184]:cyp450:"P-450 isozymes" ;[1240..1251]:substance:"fatty acids" ;[1282..1294]:substance:"hydrocarbons" ;[1298..1308]:substance:"substrates" (SENT (S (NP-SBJ (NP (NNS:[1001..1012] Comparisons)) (PP (IN:[1013..1015] of) (NP (NP (NN:[1016..1022] tissue) (NN:[1023..1035] distribution)) (,:[1035..1036] ,) (NP (NP (NN:[1038..1052] susceptibility)) (PP (TO:[1053..1055] to) (NP (NNS:[1056..1066] inhibitors)))) (,:[1066..1067] ,) (CC:[1068..1071] and) (NP (NN:[1072..1081] induction) (NNS:[1082..1092] properties))))) (VP (VBP:[1093..1100] suggest) (SBAR (IN:[1101..1105] that) (S (NP-SBJ-2 (NP (DT:[1106..1109] the) (NN:[1111..1124] hydroxylation)) (PP (IN:[1125..1127] of) (NP (NN:[1128..1132] MEHP)))) (VP (VBZ:[1133..1135] is) (ADJP-PRD (ADJP (RBR:[1136..1140] more) (JJ:[1141..1147] likely) (S (NP-SBJ-2 (-NONE-:[1147..1147] *)) (VP (TO:[1148..1150] to) (VP (VB:[1151..1153] be) (VP (VBN:[1154..1162] mediated) (NP-2 (-NONE-:[1162..1162] *)) (PP (IN:[1163..1165] by) (NP-LGS (NP (DT:[1166..1169] the) (NN:[1170..1175] P-450) (NNS:[1176..1184] isozymes)) (VP (VBN:[1186..1196] associated) (NP (-NONE-:[1196..1196] *)) (PP-CLR (IN:[1197..1201] with) (NP (NP (NP (SYM:[1202..1207] omega) (HYPH:[1207..1208] -) (NML-1 (-NONE-:[1208..1208] *P*))) (CC:[1209..1212] and) (NP (-LRB-:[1213..1214] -LRB-) (NML (SYM:[1214..1219] omega) (HYPH:[1219..1220] -) (CD:[1220..1221] 1)) (-RRB-:[1221..1222] -RRB-) (HYPH:[1222..1223] -) (NML-1 (NN:[1223..1236] hydroxylation)))) (PP (IN:[1237..1239] of) (NP (JJ:[1240..1245] fatty) (NNS:[1246..1251] acids))))))))))))) (PP (IN:[1252..1256] than) (PP (IN:[1257..1261] with) (NP (NP (DT:[1263..1268] those)) (SBAR (WHNP-3 (WDT:[1269..1273] that)) (S (NP-SBJ-3 (-NONE-:[1273..1273] *T*)) (VP (VBP:[1274..1281] utilize) (NP (NNS:[1282..1294] hydrocarbons)) (PP (IN:[1295..1297] as) (NP (NNS:[1298..1308] substrates)))))))))))))) (.:[1308..1309] .))) ;section 9 Span:1313..1357 ;PMID: 6150824 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1313..1317] PMID) (::[1317..1318] :) (CD:[1319..1326] 6150824) (NN:[1327..1328] -LSB-) (NNP:[1328..1334] PubMed) (::[1335..1336] -) (NN:[1337..1344] indexed) (IN:[1345..1348] for) (NNP:[1349..1357] MEDLINE-RSB-)))