;PMID: 2891479 ;source_file_1887.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..44] = [t:0..44] ;1)sentence:[e:50..144] = [t:50..144] ;2)sentence:[e:145..188] = [t:145..188] ;3)section:[e:192..218] = [t:192..218] ;4)section:[e:222..301] = [t:222..301] ;5)sentence:[e:305..421] = [t:305..421] ;6)sentence:[e:422..545] = [t:422..545] ;7)sentence:[e:547..679] = [t:547..679] ;8)sentence:[e:680..848] = [t:680..848] ;9)sentence:[e:849..997] = [t:849..997] ;10)sentence:[e:998..1095] = [t:998..1095] ;11)sentence:[e:1097..1330] = [t:1097..1330] ;12)sentence:[e:1332..1498] = [t:1332..1498] ;13)sentence:[e:1499..1589] = [t:1499..1589] ;14)sentence:[e:1590..1745] = [t:1590..1745] ;15)sentence:[e:1746..1983] = [t:1746..1983] ;16)section:[e:1987..2031] = [t:1987..2031] ;section 0 Span:0..44 ;Drug Metab Dispos. 1987 Sep-Oct;15(5):634-9. (SEC (FRAG (NNP:[0..4] Drug) (NNP:[5..10] Metab) (NNP:[11..17] Dispos) (.:[17..18] .) (CD:[19..23] 1987) (NN:[24..34] Sep-Oct;15) (-LRB-:[34..35] -LRB-) (CD:[35..36] 5) (-RRB-:[36..37] -RRB-) (::[37..38] :) (CD:[38..41] 634) (::[41..42] -) (CD:[42..44] 9.))) ;sentence 1 Span:50..144 ;Oxidation of the alcohol dehydrogenase inhibitor pyrazole to ;4-hydroxypyrazole by microsomes. ;[67..88]:substance:"alcohol dehydrogenase" ;[89..98]:substance:"inhibitor" ;[99..107]:substance:"pyrazole" ;[111..128]:substance:"4-hydroxypyrazole" (SENT (NP-HLN (NP (NN:[50..59] Oxidation)) (PP (IN:[60..62] of) (NP (NP (DT:[63..66] the) (NML (NN:[67..74] alcohol) (NN:[75..88] dehydrogenase)) (NN:[89..98] inhibitor)) (NP (NN:[99..107] pyrazole)))) (PP (TO:[108..110] to) (NP (NN:[111..128] 4-hydroxypyrazole))) (PP (IN:[130..132] by) (NP (NNS:[133..143] microsomes))) (.:[143..144] .))) ;sentence 2 Span:145..188 ;Effect of cytochrome P-450 inducing agents. ;[155..171]:cyp450:"cytochrome P-450" ;[181..187]:substance:"agents" (SENT (NP-HLN (NP (NN:[145..151] Effect)) (PP (IN:[152..154] of) (NP (ADJP (NML (NN:[155..165] cytochrome) (NN:[166..171] P-450)) (VBG:[172..180] inducing)) (NNS:[181..187] agents))) (.:[187..188] .))) ;section 3 Span:192..218 ;Feierman DE, Cederbaum AI. (SEC (FRAG (NNP:[192..200] Feierman) (NNP:[201..203] DE) (,:[203..204] ,) (NNP:[205..214] Cederbaum) (NNP:[215..218] AI.))) ;section 4 Span:222..301 ;Department of Biochemistry, Mount Sinai School of Medicine, New York, NY ;10029. (SEC (FRAG (NNP:[222..232] Department) (IN:[233..235] of) (NNP:[236..248] Biochemistry) (,:[248..249] ,) (NNP:[250..255] Mount) (NNP:[256..261] Sinai) (NNP:[262..268] School) (IN:[269..271] of) (NNP:[272..280] Medicine) (,:[280..281] ,) (NNP:[282..285] New) (NNP:[286..290] York) (,:[290..291] ,) (NNP:[292..294] NY) (CD:[295..300] 10029) (.:[300..301] .))) ;sentence 5 Span:305..421 ;Pyrazole and its analogues are widely used to inhibit alcohol dehydrogenase ;and to block the metabolism of ethanol. ;[305..313]:substance:"Pyrazole" ;[322..331]:substance:"analogues" ;[359..380]:substance:"alcohol dehydrogenase" ;[413..420]:substance:"ethanol" (SENT (S (NP-SBJ-1 (NP (NN:[305..313] Pyrazole)) (CC:[314..317] and) (NP (PRP$:[318..321] its) (NNS:[322..331] analogues))) (VP (VBP:[332..335] are) (VP (ADVP (RB:[336..342] widely)) (VBN:[343..347] used) (NP-1 (-NONE-:[347..347] *)) (S-PRP (NP-SBJ (-NONE-:[347..347] *)) (VP (VP (TO:[348..350] to) (VP (VB:[351..358] inhibit) (NP (NN:[359..366] alcohol) (NN:[367..380] dehydrogenase)))) (CC:[381..384] and) (VP (TO:[386..388] to) (VP (VB:[389..394] block) (NP (NP (DT:[395..398] the) (NN:[399..409] metabolism)) (PP (IN:[410..412] of) (NP (NN:[413..420] ethanol)))))))))) (.:[420..421] .))) ;sentence 6 Span:422..545 ;Experiments were conducted to demonstrate that pyrazole is oxidized to ;4-hydroxypyrazole by isolated rat liver microsomes. ;[470..478]:substance:"pyrazole" ;[494..511]:substance:"4-hydroxypyrazole" (SENT (S (NNS:[422..433] Experiments) (VP (VBD:[434..438] were) (VP (VBN:[439..448] conducted) (NP-2 (-NONE-:[448..448] *)) (S-PRP (NP-SBJ (-NONE-:[448..448] *)) (VP (TO:[449..451] to) (VP (VB:[452..463] demonstrate) (SBAR (IN:[465..469] that) (S (NP-SBJ-1 (NN:[470..478] pyrazole)) (VP (VBZ:[479..481] is) (VP (VBN:[482..490] oxidized) (NP-1 (-NONE-:[490..490] *)) (PP (TO:[491..493] to) (NP (NN:[494..511] 4-hydroxypyrazole))) (PP (IN:[512..514] by) (NP-LGS (VBN:[515..523] isolated) (NN:[524..527] rat) (NN:[528..533] liver) (NNS:[534..544] microsomes)))))))))))) (.:[544..545] .))) ;sentence 7 Span:547..679 ;A HPLC procedure employing UV and electrochemical detection was developed for ; the separation and quantitation of 4-hydroxypyrazole. ;[661..678]:substance:"4-hydroxypyrazole" (SENT (S (NP-SBJ-1 (NP (DT:[547..548] A) (NN:[549..553] HPLC) (NN:[554..563] procedure)) (VP (VBG:[564..573] employing) (NP (NP (JJ:[574..576] UV) (NML-2 (-NONE-:[576..576] *P*))) (CC:[577..580] and) (NP (JJ:[581..596] electrochemical) (NML-2 (NN:[597..606] detection)))))) (VP (VBD:[607..610] was) (VP (VBN:[611..620] developed) (NP-1 (-NONE-:[620..620] *)) (PP (IN:[621..624] for) (NP (NP (DT:[626..629] the) (NN:[630..640] separation) (CC:[641..644] and) (NN:[645..657] quantitation)) (PP (IN:[658..660] of) (NP (NN:[661..678] 4-hydroxypyrazole))))))) (.:[678..679] .))) ;sentence 8 Span:680..848 ;Pyrazole metabolism was NADPH-dependent, sensitive to inhibition by carbon ;monoxide, and was depressed in the presence of other substrates such as ;aniline or ethanol. ;[680..688]:substance:"Pyrazole" ;[705..710]:substance:"NADPH" ;[749..764]:substance:"carbon monoxide" ;[810..820]:substance:"substrates" ;[829..836]:substance:"aniline" ;[840..847]:substance:"ethanol" (SENT (S (NP-SBJ (NN:[680..688] Pyrazole) (NN:[689..699] metabolism)) (VP (VP (VBD:[700..703] was) (ADJP-PRD (ADJP (NN:[705..710] NADPH) (HYPH:[710..711] -) (JJ:[711..720] dependent)) (,:[720..721] ,) (ADJP (JJ:[722..731] sensitive) (PP (TO:[732..734] to) (NP (NP (NN:[735..745] inhibition)) (PP (IN:[746..748] by) (NP (NN:[749..755] carbon) (NN:[756..764] monoxide)))))))) (,:[764..765] ,) (CC:[766..769] and) (VP (VBD:[770..773] was) (ADJP-PRD (VBN:[774..783] depressed)) (PP (IN:[785..787] in) (NP (NP (DT:[788..791] the) (NN:[792..800] presence)) (PP (IN:[801..803] of) (NP (NP (JJ:[804..809] other) (NNS:[810..820] substrates)) (PP (JJ:[821..825] such) (IN:[826..828] as) (NP (NN:[829..836] aniline) (CC:[837..839] or) (NN:[840..847] ethanol))))))))) (.:[847..848] .))) ;sentence 9 Span:849..997 ;Prior treatment of rats with either pyrazole or 4-methylpyrazole resulted in ;an increase in pyrazole oxidation to 4-hydroxypyrazole by microsomes. ;[886..894]:substance:"pyrazole" ;[898..914]:substance:"4-methylpyrazole" ;[943..951]:substance:"pyrazole" ;[965..982]:substance:"4-hydroxypyrazole" (SENT (S (NP-SBJ (NP (JJ:[849..854] Prior) (NN:[855..864] treatment)) (PP (IN:[866..868] of) (NP (NNS:[869..873] rats))) (PP (IN:[874..878] with) (NP (CC:[879..885] either) (NP (NN:[886..894] pyrazole) (CC:[895..897] or) (NN:[898..914] 4-methylpyrazole))))) (VP (VBD:[915..923] resulted) (PP-CLR (IN:[924..926] in) (NP (NP (DT:[927..929] an) (NN:[930..938] increase)) (PP (IN:[939..941] in) (NP (NP (NN:[943..951] pyrazole) (NN:[952..961] oxidation)) (PP (TO:[962..964] to) (NP (NN:[965..982] 4-hydroxypyrazole))) (PP (IN:[983..985] by) (NP (NNS:[986..996] microsomes)))))))) (.:[996..997] .))) ;sentence 10 Span:998..1095 ;Increases were observed when rates were expressed either per mg of protein ;or per nmol of P-450. ;[1056..1073]:quantitative-units:"per mg of protein" ;[1077..1094]:quantitative-units:"per nmol of P-450" (SENT (S (NP-SBJ-2 (NNS:[998..1007] Increases)) (VP (VBD:[1008..1012] were) (VP (VBN:[1013..1021] observed) (NP-2 (-NONE-:[1021..1021] *)) (SBAR-ADV (WHADVP-3 (WRB:[1023..1027] when)) (S (NP-SBJ-1 (NNS:[1028..1033] rates)) (VP (VBD:[1034..1038] were) (VP (VBN:[1039..1048] expressed) (NP-1 (-NONE-:[1048..1048] *)) (PP (CC:[1049..1055] either) (PP (IN:[1056..1059] per) (NP (NP (NN:[1060..1062] mg)) (PP (IN:[1063..1065] of) (NP (NN:[1066..1073] protein))))) (CC:[1074..1076] or) (PP (IN:[1077..1080] per) (NP (NP (NN:[1081..1085] nmol)) (PP (IN:[1086..1088] of) (NP (NN:[1089..1094] P-450)))))) (ADVP-TMP-3 (-NONE-:[1094..1094] *T*)))))))) (.:[1094..1095] .))) ;sentence 11 Span:1097..1330 ;Microsomes from pyrazole- and 4-methylpyrazole-treated rats had Km values for ; pyrazole of about 0.29 and 0.14 mM, respectively, and Vmax values of about ;0.5 and 0.7 nmol of 4-hydroxypyrazole per min per mg of protein, ;respectively. ;[1113..1121]:substance:"pyrazole" ;[1127..1143]:substance:"4-methylpyrazole" ;[1161..1163]:quantitative-name:"Km" ;[1176..1184]:substance:"pyrazole" ;[1194..1198]:quantitative-value:"0.29" ;[1203..1207]:quantitative-value:"0.14" ;[1208..1210]:quantitative-units:"mM" ;[1230..1234]:quantitative-name:"Vmax" ;[1251..1254]:quantitative-value:"0.5" ;[1260..1263]:quantitative-value:"0.7" ;[1264..1268]:quantitative-units:"nmol" ;[1272..1289]:substance:"4-hydroxypyrazole" ;[1290..1315]:quantitative-units:"per min per mg of protein" (SENT (S (NP-SBJ (NP (NNS:[1097..1107] Microsomes)) (PP (IN:[1108..1112] from) (NP (NP (ADJP (NN:[1113..1121] pyrazole) (HYPH:[1121..1122] -) (ADJP-4 (-NONE-:[1122..1122] *P*))) (NML-5 (-NONE-:[1122..1122] *P*))) (CC:[1123..1126] and) (NP (ADJP (NN:[1127..1143] 4-methylpyrazole) (HYPH:[1143..1144] -) (ADJP-4 (VBN:[1144..1151] treated))) (NML-5 (NNS:[1152..1156] rats)))))) (VP (VBD:[1157..1160] had) (NP (NP (NP (NN:[1161..1163] Km) (NNS:[1164..1170] values)) (PP (IN:[1171..1174] for) (NP (NN:[1176..1184] pyrazole))) (PP (IN:[1185..1187] of) (NP (NP (NP (QP (ADJP-3 (RB:[1188..1193] about)) (CD:[1194..1198] 0.29)) (NML-2 (-NONE-:[1198..1198] *P*))) (CC:[1199..1202] and) (NP (QP (ADJP-3 (-NONE-:[1202..1202] *P*)) (CD:[1203..1207] 0.14)) (NML-2 (NN:[1208..1210] mM)))) (,:[1210..1211] ,) (ADVP (RB:[1212..1224] respectively))))) (,:[1224..1225] ,) (CC:[1226..1229] and) (NP (NP (NN:[1230..1234] Vmax) (NNS:[1235..1241] values)) (PP (IN:[1242..1244] of) (NP (NP (NP (NP (QP (ADJP-1 (RB:[1245..1250] about)) (CD:[1251..1254] 0.5)) (NML-6 (-NONE-:[1254..1254] *P*))) (CC:[1256..1259] and) (NP (QP (ADJP-1 (-NONE-:[1259..1259] *P*)) (CD:[1260..1263] 0.7)) (NML-6 (NN:[1264..1268] nmol)))) (PP (IN:[1269..1271] of) (NP (NN:[1272..1289] 4-hydroxypyrazole)))) (PP (IN:[1290..1293] per) (NP (NN:[1294..1297] min))) (PP (IN:[1298..1301] per) (NP (NP (NN:[1302..1304] mg)) (PP (IN:[1305..1307] of) (NP (NN:[1308..1315] protein))))) (,:[1315..1316] ,) (ADVP (RB:[1317..1329] respectively))))))) (.:[1329..1330] .))) ;sentence 12 Span:1332..1498 ;Chronic consumption of ethanol for 24 days resulted in an increase in ;pyrazole oxidation (per mg of protein and per nmol of P-450) as compared to ;pair-fed controls. ;[1355..1362]:substance:"ethanol" ;[1367..1369]:quantitative-value:"24" ;[1370..1374]:quantitative-units:"days" ;[1402..1410]:substance:"pyrazole" ;[1423..1440]:quantitative-units:"per mg of protein" ;[1445..1462]:quantitative-units:"per nmol of P-450" (SENT (S (NP-SBJ (NP (JJ:[1332..1339] Chronic) (NN:[1340..1351] consumption)) (PP (IN:[1352..1354] of) (NP (NN:[1355..1362] ethanol))) (PP (IN:[1363..1366] for) (NP (CD:[1367..1369] 24) (NNS:[1370..1374] days)))) (VP (VBD:[1375..1383] resulted) (PP-CLR (IN:[1384..1386] in) (NP (NP (DT:[1387..1389] an) (NN:[1390..1398] increase)) (PP (IN:[1399..1401] in) (NP (NN:[1402..1410] pyrazole) (NN:[1412..1421] oxidation))) (PRN (-LRB-:[1422..1423] -LRB-) (PP (PP (IN:[1423..1426] per) (NP (NP (NN:[1427..1429] mg)) (PP (IN:[1430..1432] of) (NP (NN:[1433..1440] protein))))) (CC:[1441..1444] and) (PP (IN:[1445..1448] per) (NP (NP (NN:[1449..1453] nmol)) (PP (IN:[1454..1456] of) (NP (NN:[1457..1462] P-450)))))) (-RRB-:[1462..1463] -RRB-)))) (PP (IN:[1464..1466] as) (S-NOM (NP-SBJ-1 (-NONE-:[1466..1466] *)) (VP (VBN:[1467..1475] compared) (NP-1 (-NONE-:[1475..1475] *)) (PP-CLR (TO:[1476..1478] to) (NP (ADJP (NN:[1479..1483] pair) (HYPH:[1483..1484] -) (VBN:[1484..1487] fed)) (NNS:[1489..1497] controls))))))) (.:[1497..1498] .))) ;sentence 13 Span:1499..1589 ;By contrast, phenobarbital treatment lowered the rate of production of ;4-hydroxypyrazole. ;[1512..1525]:substance:"phenobarbital" ;[1571..1588]:substance:"4-hydroxypyrazole" (SENT (S (PP (IN:[1499..1501] By) (NP (NN:[1502..1510] contrast))) (,:[1510..1511] ,) (NP-SBJ (NN:[1512..1525] phenobarbital) (NN:[1526..1535] treatment)) (VP (VBD:[1536..1543] lowered) (NP (NP (DT:[1544..1547] the) (NN:[1548..1552] rate)) (PP (IN:[1553..1555] of) (NP (NP (NN:[1556..1566] production)) (PP (IN:[1567..1569] of) (NP (NN:[1571..1588] 4-hydroxypyrazole))))))) (.:[1588..1589] .))) ;sentence 14 Span:1590..1745 ;Treatment with 3-methylcholanthrene resulted in an increase in pyrazole ;oxidation when rates were expressed per mg of protein, but not per nmol of ;P-450. ;[1605..1625]:substance:"3-methylcholanthrene" ;[1654..1662]:substance:"pyrazole" ;[1699..1716]:quantitative-units:"per mg of protein" ;[1726..1744]:quantitative-units:"per nmol of P-450" (SENT (S (NP-SBJ (NP (NN:[1590..1599] Treatment)) (PP (IN:[1600..1604] with) (NP (NN:[1605..1625] 3-methylcholanthrene)))) (VP (VBD:[1626..1634] resulted) (PP-CLR (IN:[1635..1637] in) (NP (NP (DT:[1638..1640] an) (NN:[1641..1649] increase)) (PP (IN:[1651..1653] in) (NP (NN:[1654..1662] pyrazole) (NN:[1663..1672] oxidation))))) (SBAR-ADV (WHADVP-4 (WRB:[1673..1677] when)) (S (NP-SBJ-3 (NNS:[1678..1683] rates)) (VP (VBD:[1684..1688] were) (VP (VP=1 (VBN:[1689..1698] expressed) (NP-3 (-NONE-:[1698..1698] *)) (PP=2 (IN:[1699..1702] per) (NP (NP (NN:[1703..1705] mg)) (PP (IN:[1706..1708] of) (NP (NN:[1709..1716] protein))))) (ADVP-TMP-4 (-NONE-:[1716..1716] *T*))) (,:[1716..1717] ,) (CC:[1718..1721] but) (VP=1 (RB:[1722..1725] not) (NP-3 (-NONE-:[1725..1725] *)) (PP=2 (IN:[1726..1729] per) (NP (NP (NN:[1731..1735] nmol)) (PP (IN:[1736..1738] of) (NP (NN:[1739..1744] P-450))))))))))) (.:[1744..1745] .))) ;sentence 15 Span:1746..1983 ;These results show that pyrazole is oxidized to 4-hydroxypyrazole by ;microsomes in a P-450-dependent manner and that this metabolism can be ;increased by certain inducers, e.g. pyrazole, 4-methylpyrazole, and chronic ;ethanol treatment. ;[1770..1778]:substance:"pyrazole" ;[1794..1811]:substance:"4-hydroxypyrazole" ;[1832..1837]:cyp450:"P-450" ;[1909..1917]:substance:"inducers" ;[1924..1932]:substance:"pyrazole" ;[1934..1950]:substance:"4-methylpyrazole" ;[1965..1972]:substance:"ethanol" (SENT (S (NP-SBJ (DT:[1746..1751] These) (NNS:[1752..1759] results)) (VP (VBP:[1760..1764] show) (SBAR (SBAR (IN:[1765..1769] that) (S (NP-SBJ-2 (NN:[1770..1778] pyrazole)) (VP (VBZ:[1779..1781] is) (VP (NP (VBN:[1782..1790] oxidized) (NP-2 (-NONE-:[1790..1790] *))) (PP (TO:[1791..1793] to) (NP (NN:[1794..1811] 4-hydroxypyrazole))) (PP (IN:[1813..1815] by) (NP (NNS:[1816..1826] microsomes))) (PP-MNR (IN:[1827..1829] in) (NP (DT:[1830..1831] a) (ADJP (NN:[1832..1837] P-450) (HYPH:[1837..1838] -) (JJ:[1838..1847] dependent)) (NN:[1848..1854] manner))))))) (CC:[1855..1858] and) (SBAR (IN:[1859..1863] that) (S (NP-SBJ-1 (DT:[1864..1868] this) (NN:[1869..1879] metabolism)) (VP (MD:[1880..1883] can) (VP (VB:[1884..1886] be) (VP (VBN:[1888..1897] increased) (NP-1 (-NONE-:[1897..1897] *)) (PP (IN:[1898..1900] by) (NP (NP-LGS (JJ:[1901..1908] certain) (NNS:[1909..1917] inducers)) (,:[1917..1918] ,) (PP (FW:[1919..1923] e.g.) (NP (NP (NN:[1924..1932] pyrazole)) (,:[1932..1933] ,) (NP (NN:[1934..1950] 4-methylpyrazole)) (,:[1950..1951] ,) (CC:[1952..1955] and) (NP (JJ:[1956..1963] chronic) (NN:[1965..1972] ethanol) (NN:[1973..1982] treatment))))))))))))) (.:[1982..1983] .))) ;section 16 Span:1987..2031 ;PMID: 2891479 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1987..1991] PMID) (::[1991..1992] :) (CD:[1993..2000] 2891479) (NN:[2001..2002] -LSB-) (NNP:[2002..2008] PubMed) (::[2009..2010] -) (NN:[2011..2018] indexed) (IN:[2019..2022] for) (NNP:[2023..2031] MEDLINE-RSB-)))