;PMID: 9328296 ;source_file_1783.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..46] = [t:0..46] ;1)sentence:[e:52..162] = [t:52..162] ;2)section:[e:166..188] = [t:166..188] ;3)section:[e:192..255] = [t:192..255] ;4)sentence:[e:259..446] = [t:259..446] ;5)sentence:[e:447..689] = [t:447..689] ;6)sentence:[e:690..842] = [t:690..842] ;7)sentence:[e:843..945] = [t:843..945] ;8)sentence:[e:946..1104] = [t:946..1104] ;9)sentence:[e:1105..1232] = [t:1105..1232] ;10)sentence:[e:1233..1396] = [t:1233..1396] ;11)sentence:[e:1397..1619] = [t:1397..1619] ;12)sentence:[e:1620..1971] = [t:1620..1971] ;13)sentence:[e:1972..2059] = [t:1972..2059] ;14)sentence:[e:2060..2218] = [t:2060..2218] ;15)sentence:[e:2219..2440] = [t:2219..2440] ;16)sentence:[e:2441..2607] = [t:2441..2607] ;17)section:[e:2611..2655] = [t:2611..2655] ;section 0 Span:0..46 ;Arch Biochem Biophys. 1997 Oct 1;346(1):161-9. (SEC (FRAG (NNP:[0..4] Arch) (NNP:[5..12] Biochem) (NNP:[13..20] Biophys) (.:[20..21] .) (CD:[22..26] 1997) (NNP:[27..30] Oct) (CD:[31..36] 1;346) (-LRB-:[36..37] -LRB-) (CD:[37..38] 1) (-RRB-:[38..39] -RRB-) (CD:[39..43] :161) (::[43..44] -) (CD:[44..46] 9.))) ;sentence 1 Span:52..162 ;Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, ;and 3A4 in human liver microsomes. ;[52..64]:substance:"Progesterone" ;[69..81]:substance:"testosterone" ;[99..120]:cyp450:"cytochromes P450 2C19" ;[99..115]...[132..135]:cyp450:"cytochromes P450"..."3A4" ;[99..115]...[122..125]:cyp450:"cytochromes P450"..."2C9" (SENT (NP-HLN (NP (NP (NN:[52..64] Progesterone) (NML-2 (-NONE-:[64..64] *P*))) (CC:[65..68] and) (NP (NN:[69..81] testosterone) (NML-2 (NN:[82..95] hydroxylation)))) (PP (IN:[96..98] by) (NP (NP (NML-1 (NNS:[99..110] cytochromes) (NN:[111..115] P450)) (NN:[116..120] 2C19)) (,:[120..121] ,) (NP (NML-1 (-NONE-:[121..121] *P*)) (NN:[122..125] 2C9)) (,:[125..126] ,) (CC:[127..130] and) (NP (NML-1 (-NONE-:[130..130] *P*)) (NN:[132..135] 3A4)))) (PP-LOC (IN:[136..138] in) (NP (JJ:[139..144] human) (NN:[145..150] liver) (NNS:[151..161] microsomes))) (.:[161..162] .))) ;section 2 Span:166..188 ;Yamazaki H, Shimada T. (SEC (FRAG (NNP:[166..174] Yamazaki) (NNP:[175..177] H,) (NNP:[178..185] Shimada) (NNP:[186..188] T.))) ;section 3 Span:192..255 ;Osaka Prefectural Institute of Public Health, Nakamichi, Japan. (SEC (FRAG (NNP:[192..197] Osaka) (NNP:[198..209] Prefectural) (NNP:[210..219] Institute) (IN:[220..222] of) (NNP:[223..229] Public) (NNP:[230..236] Health) (,:[236..237] ,) (NNP:[238..247] Nakamichi) (,:[247..248] ,) (NNP:[249..254] Japan) (.:[254..255] .))) ;sentence 4 Span:259..446 ;Roles of human cytochrome P450 (P450 or CYP) 2C9, 2C19, and 3A4 in the ;oxidation of progesterone and testosterone were studied in recombinant P450 ;enzymes and in human liver microsomes. ;[274..307]:cyp450:"cytochrome P450 (P450 or CYP) 2C9" ;[274..303]...[319..322]:cyp450:"cytochrome P450 (P450 or CYP)"..."3A4" ;[274..303]...[309..313]:cyp450:"cytochrome P450 (P450 or CYP)"..."2C19" ;[344..356]:substance:"progesterone" ;[361..373]:substance:"testosterone" ;[402..414]:cyp450:"P450 enzymes" (SENT (S (NP-SBJ-2 (NP (NNS:[259..264] Roles)) (PP (IN:[265..267] of) (NP (NP (NML-1 (NML (JJ:[268..273] human) (NN:[274..284] cytochrome) (NN:[285..289] P450)) (NML (-LRB-:[290..291] -LRB-) (NN:[291..295] P450) (CC:[296..298] or) (NN:[299..302] CYP) (-RRB-:[302..303] -RRB-))) (NN:[304..307] 2C9)) (,:[307..308] ,) (NP (NML-1 (-NONE-:[308..308] *P*)) (NN:[309..313] 2C19)) (,:[313..314] ,) (CC:[315..318] and) (NP (NML-1 (-NONE-:[318..318] *P*)) (NN:[319..322] 3A4)))) (PP-LOC (IN:[323..325] in) (NP (NP (DT:[326..329] the) (NN:[330..339] oxidation)) (PP (IN:[341..343] of) (NP (NN:[344..356] progesterone) (CC:[357..360] and) (NN:[361..373] testosterone)))))) (VP (VBD:[374..378] were) (VP (VBN:[379..386] studied) (NP-2 (-NONE-:[386..386] *)) (PP-LOC (PP (IN:[387..389] in) (NP (JJ:[390..401] recombinant) (NN:[402..406] P450) (NNS:[407..414] enzymes))) (CC:[415..418] and) (PP (IN:[419..421] in) (NP (JJ:[423..428] human) (NN:[429..434] liver) (NNS:[435..445] microsomes)))))) (.:[445..446] .))) ;sentence 5 Span:447..689 ;In vitro inhibition experiments showed that progesterone and its 17alpha- ;and 21-hydroxylated metabolites and 11-deoxycortisol suppressed the ;CYP2C19-dependent R-warfarin 7-hydroxylation activities, with progesterone ;being the most active. ;[491..503]:substance:"progesterone" ;[513..521]...[542..553]:substance:"17alpha-"..."metabolites" ;[526..553]:substance:"21-hydroxylated metabolites" ;[558..574]:substance:"11-deoxycortisol" ;[591..598]:cyp450:"CYP2C19" ;[609..619]:substance:"R-warfarin" ;[653..665]:substance:"progesterone" (SENT (S (NP-SBJ (ADJP (FW:[447..449] In) (FW:[450..455] vitro)) (NN:[456..466] inhibition) (NNS:[467..478] experiments)) (VP (VBD:[479..485] showed) (SBAR (IN:[486..490] that) (S (NP-SBJ (NP (NN:[491..503] progesterone)) (CC:[505..508] and) (NP (PRP$:[509..512] its) (NML (NML (ADJP (NN:[513..520] 17alpha) (HYPH:[520..521] -) (ADJP-1 (-NONE-:[521..521] *P*))) (NML-2 (-NONE-:[521..521] *P*))) (CC:[522..525] and) (NML (ADJP (CD:[526..528] 21) (HYPH:[528..529] -) (ADJP-1 (VBN:[529..541] hydroxylated))) (NML-2 (NNS:[542..553] metabolites))))) (CC:[554..557] and) (NP (NN:[558..574] 11-deoxycortisol))) (VP (VBD:[575..585] suppressed) (NP (DT:[587..590] the) (NML (ADJP (NN:[591..598] CYP2C19) (HYPH:[598..599] -) (JJ:[599..608] dependent)) (NN:[609..619] R-warfarin) (NN:[620..635] 7-hydroxylation)) (NNS:[636..646] activities)) (,:[646..647] ,) (PP (IN:[648..652] with) (NP (NP (NN:[653..665] progesterone)) (VP (VBG:[667..672] being) (NP-PRD (DT:[673..676] the) (RBS:[677..681] most) (JJ:[682..688] active))))))))) (.:[688..689] .))) ;sentence 6 Span:690..842 ;These steroid chemicals also inhibited CYP2C9-dependent S-warfarin ;7-hydroxylation activities though lesser extents seen with those in CYP2C19 ;enzyme. ;[696..713]:substance:"steroid chemicals" ;[729..735]:cyp450:"CYP2C9" ;[747..757]:substance:"S-warfarin" ;[827..841]:cyp450:"CYP2C19 enzyme" (SENT (S (NP-SBJ (DT:[690..695] These) (JJ:[696..703] steroid) (NNS:[704..713] chemicals)) (ADVP (RB:[714..718] also)) (VP (VBD:[719..728] inhibited) (NP (NML (ADJP (NN:[729..735] CYP2C9) (HYPH:[735..736] -) (JJ:[736..745] dependent)) (NN:[747..757] S-warfarin) (NN:[758..773] 7-hydroxylation)) (NNS:[774..784] activities)) (SBAR-ADV (IN:[785..791] though) (S (NP-SBJ-1 (JJR:[792..798] lesser) (NNS:[799..806] extents)) (VP (VBN:[807..811] seen) (NP-1 (-NONE-:[811..811] *)) (PP (IN:[812..816] with) (NP (NP (DT:[817..822] those)) (PP-LOC (IN:[823..825] in) (NP (NN:[827..834] CYP2C19) (NN:[835..841] enzyme))))))))) (.:[841..842] .))) ;sentence 7 Span:843..945 ;Progesterone was found to be a competitive inhibitor of CYP2C19 and CYP2C9 ;in human liver microsomes. ;[843..855]:substance:"Progesterone" ;[886..895]:substance:"inhibitor" ;[899..906]:cyp450:"CYP2C19" ;[912..918]:cyp450:"CYP2C9" (SENT (S (NP-SBJ-1 (NN:[843..855] Progesterone)) (VP (VBD:[856..859] was) (VP (VBN:[860..865] found) (NP-1 (-NONE-:[865..865] *)) (S (NP-SBJ-1 (-NONE-:[865..865] *)) (VP (TO:[866..868] to) (VP (VB:[869..871] be) (NP-PRD (NP (DT:[872..873] a) (JJ:[874..885] competitive) (NN:[886..895] inhibitor)) (PP (IN:[896..898] of) (NP (NN:[899..906] CYP2C19) (CC:[908..911] and) (NN:[912..918] CYP2C9)))) (PP-LOC (IN:[919..921] in) (NP (JJ:[922..927] human) (NN:[928..933] liver) (NNS:[934..944] microsomes)))))))) (.:[944..945] .))) ;sentence 8 Span:946..1104 ;Recombinant CYP2C19 catalyzed progesterone to form 21-hydroxyprogesterone as ;a major product and 16alpha- and 17alpha-hydroxyprogesterone as minor ;products. ;[958..965]:cyp450:"CYP2C19" ;[976..988]:substance:"progesterone" ;[998..1020]:substance:"21-hydroxyprogesterone" ;[1044..1052]...[1066..1085]:substance:"16alpha-"..."hydroxyprogesterone" ;[1058..1085]:substance:"17alpha-hydroxyprogesterone" (SENT (S (NP-SBJ (JJ:[946..957] Recombinant) (NN:[958..965] CYP2C19)) (VP (VBD:[966..975] catalyzed) (NP (NN:[976..988] progesterone)) (S-ADV (NP-SBJ (-NONE-:[988..988] *)) (VP (TO:[990..992] to) (VP (VB:[993..997] form) (NP (NP (NP (NN:[998..1020] 21-hydroxyprogesterone)) (PP (IN:[1021..1023] as) (NP (DT:[1024..1025] a) (JJ:[1026..1031] major) (NN:[1032..1039] product)))) (CC:[1040..1043] and) (NP (NP (NP (NN:[1044..1051] 16alpha) (HYPH:[1051..1052] -) (NML-1 (-NONE-:[1052..1052] *P*))) (CC:[1053..1056] and) (NP (NN:[1058..1065] 17alpha) (HYPH:[1065..1066] -) (NML-1 (NN:[1066..1085] hydroxyprogesterone)))) (PP (IN:[1086..1088] as) (NP (JJ:[1089..1094] minor) (NNS:[1095..1103] products))))))))) (.:[1103..1104] .))) ;sentence 9 Span:1105..1232 ;CYP2C9 also had progesterone 21-hydroxylation activities, although the ;activities were lower than those catalyzed by CYP2C19. ;[1105..1111]:cyp450:"CYP2C9" ;[1121..1133]:substance:"progesterone" ;[1224..1231]:cyp450:"CYP2C19" (SENT (S (NP-SBJ (NN:[1105..1111] CYP2C9)) (ADVP (RB:[1112..1116] also)) (VP (VBD:[1117..1120] had) (NP (NN:[1121..1133] progesterone) (NN:[1135..1151] 21-hydroxylation) (NNS:[1152..1162] activities)) (,:[1162..1163] ,) (SBAR-ADV (IN:[1164..1172] although) (S (NP-SBJ (DT:[1173..1176] the) (NNS:[1177..1187] activities)) (VP (VBD:[1188..1192] were) (ADJP-PRD (ADJP (JJR:[1193..1198] lower)) (PP (IN:[1199..1203] than) (NP (NP (DT:[1204..1209] those)) (VP (VBN:[1211..1220] catalyzed) (NP (-NONE-:[1220..1220] *)) (PP (IN:[1221..1223] by) (NP-LGS (NN:[1224..1231] CYP2C19))))))))))) (.:[1231..1232] .))) ;sentence 10 Span:1233..1396 ;Vmax/Km ratios for the progesterone 21-hydroxylation activity of CYP2C19 ;were determined to be 13- and 32-fold higher than those of CYP2C9 and 3A4, ;respectively. ;[1233..1240]:quantitative-name:"Vmax/Km" ;[1256..1268]:substance:"progesterone" ;[1299..1306]:cyp450:"CYP2C19" ;[1329..1332]...[1340..1344]:quantitative-value:"13-"..."fold" ;[1337..1344]:quantitative-value:"32-fold" ;[1367..1373]:cyp450:"CYP2C9" ;[1367..1370]...[1378..1381]:cyp450:"CYP"..."3A4" (SENT (S (NP-SBJ-4 (NP (NML (NML (NN:[1233..1237] Vmax)) (PP (SYM:[1237..1238] /) (NP (NN:[1238..1240] Km)))) (NNS:[1241..1247] ratios)) (PP (IN:[1248..1251] for) (NP (NP (DT:[1252..1255] the) (NN:[1256..1268] progesterone) (NN:[1269..1285] 21-hydroxylation) (NN:[1287..1295] activity)) (PP (IN:[1296..1298] of) (NP-SBJ (NN:[1299..1306] CYP2C19)))))) (VP (VBD:[1307..1311] were) (VP (VBN:[1312..1322] determined) (S (NP-SBJ-4 (-NONE-:[1322..1322] *)) (VP (TO:[1323..1325] to) (VP (VB:[1326..1328] be) (ADJP-PRD (ADJP (ADJP (ADVP-EXT (CD:[1329..1331] 13) (HYPH:[1331..1332] -) (ADVP-2 (-NONE-:[1332..1332] *P*))) (ADJP-3 (-NONE-:[1332..1332] *P*))) (CC:[1333..1336] and) (ADJP (ADVP-EXT (CD:[1337..1339] 32) (HYPH:[1339..1340] -) (ADVP-2 (RB:[1340..1344] fold))) (ADJP-3 (JJR:[1345..1351] higher)))) (PP (IN:[1352..1356] than) (NP (NP (DT:[1357..1362] those)) (PP (IN:[1363..1365] of) (NP (NP (NML-1 (NN:[1367..1370] CYP)) (NN:[1370..1373] 2C9)) (CC:[1374..1377] and) (NP (NML-1 (-NONE-:[1377..1377] *P*)) (NN:[1378..1381] 3A4)) (,:[1381..1382] ,) (ADVP (RB:[1383..1395] respectively)))))))))))) (.:[1395..1396] .))) ;sentence 11 Span:1397..1619 ;CYP3A4 oxidized progesterone to form 16alpha-, 6beta-, and ;2beta-hydroxyprogesterone as major products and 21-hydroxyprogesterone as a ;minor product, but did not produce detectable levels of ;17alpha-hydroxyprogesterone. ;[1397..1403]:cyp450:"CYP3A4" ;[1413..1425]:substance:"progesterone" ;[1434..1442]...[1463..1482]:substance:"16alpha-"..."hydroxyprogesterone" ;[1445..1451]...[1463..1482]:substance:"6beta-"..."hydroxyprogesterone" ;[1457..1482]:substance:"2beta-hydroxyprogesterone" ;[1506..1528]:substance:"21-hydroxyprogesterone" ;[1591..1618]:substance:"17alpha-hydroxyprogesterone" (SENT (S (NP-SBJ (NN:[1397..1403] CYP3A4)) (VP (VP (VBD:[1404..1412] oxidized) (NP (NN:[1413..1425] progesterone)) (S-ADV (NP-SBJ (-NONE-:[1425..1425] *)) (VP (TO:[1426..1428] to) (VP (VB:[1429..1433] form) (NP (NP (NP (NP (NN:[1434..1441] 16alpha) (HYPH:[1441..1442] -) (NML-1 (-NONE-:[1442..1442] *P*))) (,:[1442..1443] ,) (NP (NN:[1445..1450] 6beta) (HYPH:[1450..1451] -) (NML-1 (-NONE-:[1451..1451] *P*))) (,:[1451..1452] ,) (CC:[1453..1456] and) (NP (NN:[1457..1462] 2beta) (HYPH:[1462..1463] -) (NML-1 (NN:[1463..1482] hydroxyprogesterone)))) (PP (IN:[1483..1485] as) (NP (JJ:[1486..1491] major) (NNS:[1492..1500] products)))) (CC:[1501..1504] and) (NP (NP (NN:[1506..1528] 21-hydroxyprogesterone)) (PP (IN:[1529..1531] as) (NP (DT:[1532..1533] a) (JJ:[1534..1539] minor) (NN:[1540..1547] product))))))))) (,:[1547..1548] ,) (CC:[1549..1552] but) (VP (VBD:[1553..1556] did) (RB:[1557..1560] not) (VP (VB:[1561..1568] produce) (NP (NP (JJ:[1569..1579] detectable) (NNS:[1580..1586] levels)) (PP (IN:[1588..1590] of) (NP (NN:[1591..1618] 17alpha-hydroxyprogesterone))))))) (.:[1618..1619] .))) ;sentence 12 Span:1620..1971 ;Immunoinhibition experiments suggested that anti-CYP2C9 (which inhibits both ;CYP2C9 and CYP2C19 catalytic activities) suppressed the progesterone ;21-hydroxylation activities catalyzed by liver microsomes of humans and ;monkeys and that anti-CYP2C11 inhibited the progesterone 21-hydroxylation ;activities catalyzed by liver microsomes of male rats. ;[1665..1676]:substance:"anti-CYP2C9" ;[1698..1704]:cyp450:"CYP2C9" ;[1709..1716]:cyp450:"CYP2C19" ;[1755..1767]:substance:"progesterone" ;[1858..1870]:substance:"anti-CYP2C11" ;[1886..1898]:substance:"progesterone" (SENT (S (NP-SBJ (NN:[1620..1636] Immunoinhibition) (NNS:[1637..1648] experiments)) (VP (VBD:[1649..1658] suggested) (SBAR (SBAR (IN:[1659..1663] that) (S (NP-SBJ (NP (AFX:[1665..1669] anti) (HYPH:[1669..1670] -) (NN:[1670..1676] CYP2C9)) (PRN (-LRB-:[1677..1678] -LRB-) (SBAR (WHNP-2 (WDT:[1678..1683] which)) (S (NP-SBJ-2 (-NONE-:[1683..1683] *T*)) (VP (VBZ:[1684..1692] inhibits) (NP (CC:[1693..1697] both) (NP (NN:[1698..1704] CYP2C9) (NML-1 (-NONE-:[1704..1704] *P*))) (CC:[1705..1708] and) (NP (NN:[1709..1716] CYP2C19) (NML-1 (JJ:[1717..1726] catalytic) (NNS:[1727..1737] activities))))))) (-RRB-:[1737..1738] -RRB-))) (VP (VBD:[1740..1750] suppressed) (NP (NP (DT:[1751..1754] the) (NN:[1755..1767] progesterone) (NN:[1768..1784] 21-hydroxylation) (NNS:[1785..1795] activities)) (VP (VBN:[1796..1805] catalyzed) (NP (-NONE-:[1805..1805] *)) (PP (IN:[1806..1808] by) (NP-LGS (NP (NN:[1809..1814] liver) (NNS:[1816..1826] microsomes)) (PP (IN:[1827..1829] of) (NP (NNS:[1830..1836] humans) (CC:[1837..1840] and) (NNS:[1841..1848] monkeys)))))))))) (CC:[1849..1852] and) (SBAR (IN:[1853..1857] that) (S (NP-SBJ (AFX:[1858..1862] anti) (HYPH:[1862..1863] -) (NN:[1863..1870] CYP2C11)) (VP (VBD:[1871..1880] inhibited) (NP (NP (DT:[1881..1884] the) (NN:[1886..1898] progesterone) (NN:[1899..1915] 21-hydroxylation) (NNS:[1916..1926] activities)) (VP (VBN:[1927..1936] catalyzed) (NP (-NONE-:[1936..1936] *)) (PP (IN:[1937..1939] by) (NP-LGS (NP (NN:[1940..1945] liver) (NNS:[1946..1956] microsomes)) (PP (IN:[1957..1959] of) (NP (JJ:[1960..1964] male) (NNS:[1966..1970] rats)))))))))))) (.:[1970..1971] .))) ;sentence 13 Span:1972..2059 ;CYP2C19 was also found to oxidize testosterone at 17-position to form ;androstenedione. ;[1972..1979]:cyp450:"CYP2C19" ;[2006..2018]:substance:"testosterone" ;[2043..2058]:substance:"androstenedione" (SENT (S (NP-SBJ-1 (NN:[1972..1979] CYP2C19)) (VP (VBD:[1980..1983] was) (ADVP (RB:[1984..1988] also)) (VP (VBN:[1989..1994] found) (S (NP-SBJ-1 (-NONE-:[1994..1994] *)) (VP (TO:[1995..1997] to) (VP (VB:[1998..2005] oxidize) (NP (NN:[2006..2018] testosterone)) (PP-LOC (IN:[2019..2021] at) (NP (CD:[2022..2024] 17) (HYPH:[2024..2025] -) (NN:[2025..2033] position))) (S-ADV (NP-SBJ (-NONE-:[2033..2033] *)) (VP (TO:[2034..2036] to) (VP (VB:[2037..2041] form) (NP (NN:[2043..2058] androstenedione)))))))))) (.:[2058..2059] .))) ;sentence 14 Span:2060..2218 ;Androstenedione formation catalyzed by liver microsomes of humans and ;monkeys and of male rats was suppressed by anti-CYP2C9 and anti-CYP2C11, ;respectively. ;[2060..2075]:substance:"Androstenedione" ;[2174..2185]:substance:"anti-CYP2C9" ;[2191..2203]:substance:"anti-CYP2C11" (SENT (S (NP-SBJ-1 (NP (NN:[2060..2075] Androstenedione) (NN:[2076..2085] formation)) (VP (VBN:[2086..2095] catalyzed) (NP (-NONE-:[2095..2095] *)) (PP (IN:[2096..2098] by) (NP-LGS (NP (NN:[2099..2104] liver) (NNS:[2105..2115] microsomes)) (PP (PP (IN:[2116..2118] of) (NP (NNS:[2120..2126] humans) (CC:[2127..2130] and) (NNS:[2131..2138] monkeys))) (CC:[2139..2142] and) (PP (IN:[2143..2145] of) (NP (JJ:[2146..2150] male) (NNS:[2151..2155] rats)))))))) (VP (VBD:[2156..2159] was) (VP (VBN:[2160..2170] suppressed) (NP-1 (-NONE-:[2170..2170] *)) (PP (IN:[2171..2173] by) (NP-LGS (NP (AFX:[2174..2178] anti) (HYPH:[2178..2179] -) (NN:[2179..2185] CYP2C9)) (CC:[2186..2189] and) (NP (AFX:[2191..2195] anti) (HYPH:[2195..2196] -) (NN:[2196..2203] CYP2C11)))) (,:[2203..2204] ,) (ADVP (RB:[2205..2217] respectively)))) (.:[2217..2218] .))) ;sentence 15 Span:2219..2440 ;These results suggest that CYP2C19 plays important roles in the oxidation of ;progesterone and testosterone in human liver microsomes, although the ;physiological significance of these metabolic pathways remains unclear. ;[2246..2253]:cyp450:"CYP2C19" ;[2297..2309]:substance:"progesterone" ;[2314..2326]:substance:"testosterone" (SENT (S (NP-SBJ (DT:[2219..2224] These) (NNS:[2225..2232] results)) (VP (VBP:[2233..2240] suggest) (SBAR (IN:[2241..2245] that) (S (NP-SBJ (NN:[2246..2253] CYP2C19)) (VP (VBZ:[2254..2259] plays) (NP (NP (JJ:[2260..2269] important) (NNS:[2271..2276] roles)) (PP (IN:[2277..2279] in) (NP (NP (DT:[2280..2283] the) (NN:[2284..2293] oxidation)) (PP (IN:[2294..2296] of) (NP (NN:[2297..2309] progesterone) (CC:[2310..2313] and) (NN:[2314..2326] testosterone)))))) (PP-LOC (IN:[2327..2329] in) (NP (JJ:[2330..2335] human) (NN:[2336..2341] liver) (NNS:[2343..2353] microsomes)))))) (,:[2353..2354] ,) (SBAR-ADV (IN:[2355..2363] although) (S (NP-SBJ (NP (DT:[2364..2367] the) (JJ:[2368..2381] physiological) (NN:[2382..2394] significance)) (PP (IN:[2395..2397] of) (NP (DT:[2398..2403] these) (JJ:[2404..2413] metabolic) (NNS:[2414..2422] pathways)))) (VP (VBZ:[2424..2431] remains) (ADJP-PRD (JJ:[2432..2439] unclear)))))) (.:[2439..2440] .))) ;sentence 16 Span:2441..2607 ;CYP2C9 may have some, but lesser extent than those by CYP2C19, of the ;catalytic roles for the metabolism of progesterone and testosterone by human ;liver microsomes. ;[2441..2447]:cyp450:"CYP2C9" ;[2495..2502]:cyp450:"CYP2C19" ;[2550..2562]:substance:"progesterone" ;[2567..2579]:substance:"testosterone" (SENT (S (NP-SBJ (NN:[2441..2447] CYP2C9)) (VP (MD:[2448..2451] may) (VP (VB:[2452..2456] have) (NP (NP (UCP (QP (DT:[2457..2461] some)) (,:[2461..2462] ,) (CC:[2463..2466] but) (ADJP (JJR:[2467..2473] lesser) (NN:[2474..2480] extent) (PP (IN:[2481..2485] than) (NP (NP (DT:[2486..2491] those)) (PP (IN:[2492..2494] by) (NP (NN:[2495..2502] CYP2C19)))))))) (,:[2502..2503] ,) (PP-1 (IN:[2505..2507] of) (NP (NP (DT:[2508..2511] the) (JJ:[2512..2521] catalytic) (NNS:[2522..2527] roles)) (PP (IN:[2528..2531] for) (NP (NP (DT:[2532..2535] the) (NN:[2536..2546] metabolism)) (PP (IN:[2547..2549] of) (NP (NN:[2550..2562] progesterone) (CC:[2563..2566] and) (NN:[2567..2579] testosterone))) (PP (IN:[2580..2582] by) (NP (JJ:[2584..2589] human) (NN:[2590..2595] liver) (NNS:[2596..2606] microsomes)))))))))) (.:[2606..2607] .))) ;section 17 Span:2611..2655 ;PMID: 9328296 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2611..2615] PMID) (::[2615..2616] :) (CD:[2617..2624] 9328296) (NN:[2625..2626] -LSB-) (NNP:[2626..2632] PubMed) (::[2633..2634] -) (NN:[2635..2642] indexed) (IN:[2643..2646] for) (NNP:[2647..2655] MEDLINE-RSB-)))