Pathway Map Details
Object list (links open in MetaCore):
COMT, CYP1A1, 220.127.116.11, 17 beta-estradiol, Estradiol 3-glucuronide, SULT1A3, 18.104.22.168, 22.214.171.124, 17beta-estra-1,3,5-trien-3,17-diol 3-sulfate, 126.96.36.199, UGT2B11, UGT1A10, methoxyestradiol, 188.8.131.52, 4-hydroxy- estradiol, CYP2C9, UGT2B28, SULT1E1, CYP3A4, CYP1B1, 2-hydroxy-Estradiol, SULT1A1, CYP2D6, 17beta-estra-1,3,5-trien-3,4,17-triol 4-methyl ether, 184.108.40.206, 16alpha,17beta-estra-1,3,5-trien-3,16,17-triol 16-D-glucuronoside, CYP2C8, 220.127.116.11, estriol, SULT2A1, CYP3A5, CYP2C19, 18.104.22.168, UGT1A1, CYP1A2
Endogenous and exogenous estrogens undergo oxidative metabolism by hepatic microsomal cytochrome P-450. Aromatic hydroxylation at either the C2 or C4 position is a major route of Estradiol metabolism in humans and other mammals, although there is less 4-hydroxylation than 2-hydroxylation.
Several cytochrome P450 isoforms including Cytochrome P450, family 2, subfamily C, polypeptides 8 ( CYP2C8 )  and 9 ( CYP2C9 ) , Cytochrome P450, family 3, subfamily A, polypeptides 4 ( CYP3A4 )  and 5 ( CYP3A5 ) , Cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6 ) , Cytochrome P450, family 1, subfamily A, polypeptides 1 ( CYP1A1 )  and 2 ( CYP1A2 ) , Cytochrome P450, family 1, subfamily B, polypeptide 1 ( CYP1B1 )  and Cytochrome P450, family 2, subfamily C, polypeptide 19 ( CYP2C19 )  were shown to catalyze hydroxylation of Estradiol to 2-Hydroxyestradiol or/and 4-Hydroxyestradiol. Furthermore, Catechol-O-methyltransferase ( COMT ) catalyzes the methylation of 2-Hydroxyestradiol and 4-Hydroxyestradiol to 2-Methoxyestradiol and 4-Metoxyestradiol, respectively .
Cytochrome 450 isoforms CYP1A2 and CYP3A4 catalyzes the 16alpha-hydroxylation of Estradiol forming Estriol . Estriol is glucuronidated to Estriol 16-D-glucuronoside by UDP glucuronosyltransferase 2 family, polypeptide B11 ( UGT2B11 ) .
Other pathways of Estradiol metabolism include formation of glucuronide conjugates and sulfation. UDP glucuronosyltransferase 1 family, polypeptides A1 ( UGT1A1 )  and A10 ( UGT1A10 ) , and UDP glucuronosyltransferase 2 family, polypeptide B28 ( UGT2B28 )  convert Estradiol to Estradiol 3-glucuronide.
Several sulfotransferases including Sulfotransferase family, cytosolic, 1A, phenol-preferring, members 1 ( SULT1A1 )  and 3 ( SULT1A3 ) , Sulfotransferase family 1E, estrogen-preferring, member 1 ( SULT1E1 )  and Sulfotransferase family, cytosolic, 2A, dehydroepiandrosterone (DHEA)-preferring, member 1 ( SULT2A1 )  catalyze sulfation of Estradiol to 17beta-Estra-1,3,5-trien-3,17-diol 3-sulfate.
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