About this pathway
The liver is a site for biosynthesis of estrogens but it is also the main site for further biotransformation of them. Once the estrogens are synthesized by aromatase in peripheral tissues including the liver, they will be released to the circulation. Estrone is in equilibrium with estradiol and 17-b-hydroxysteroid dehydrogenase (17bHSD) in this respect. The estrogens are taken up by the liver where they will be biotransformed further in to different metabolites. The major oxidative routes of estrone and estradiol are 2- and 4-hydroxylation by cytochrome P450 (CYP) 2B1, 1A and 3A. Other minor oxidative pathways are also identified (not shown in the pathway). The 2- and 4-hydroxy derivatives (and other metabolites) will be further converted to 2- and 4-methoxy metabolites by catechol-O-methyltransferase (COMT). While the hydroxylated metabolites appear to result in DNA damage and contribute to the tumerogenic effect of estrogen, the methoxy-derivatives appear to exhibit beneficial cardiovascular effects. Estrone and estradiol and their metabolites undergo sulfation by sulfotransferases (SULTs) and glucuronidation by glucoronyltransferases (UGTs). Estrone and estradiol sulfates could be deconjugated by sulfatases (STs).
Reactions & interactions (26)
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Biochemical Reaction
estradiol → 2-hydroxyestradiol
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Biochemical Reaction
4-hydroxyestradiol → 4-methoxyestradiol
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Biochemical Reaction
estradiol → 4-hydroxyestradiol
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Biochemical Reaction
testosterone → estradiol
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Biochemical Reaction
estrone → estradiol
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Biochemical Reaction
androstenedione → testosterone
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Biochemical Reaction
estrone → estrone sulfate
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Biochemical Reaction
androstenedione → estrone
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Biochemical Reaction
2-hydroxyestradiol → 2-methoxyestradiol
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP1A1 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP1B1 → Biochemical Reaction
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Catalysis
CYP3A5 → Biochemical Reaction
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Catalysis
COMT → Biochemical Reaction
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Catalysis
CYP1A1 → Biochemical Reaction
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Catalysis
CYP3A5 → Biochemical Reaction
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Catalysis
CYP1B1 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP19A1 → Biochemical Reaction
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Catalysis
HSD17B1 → Biochemical Reaction
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Catalysis
HSD17B1 → Biochemical Reaction
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Catalysis
SULT1A1 → Biochemical Reaction
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Catalysis
CYP19A1 → Biochemical Reaction
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Catalysis
COMT → Biochemical Reaction
Edit history (3)
- 2005-08-20 Create
- 2011-04-18 Update
- 2024-09-06 Update Updated figure to remove obsolete CYP3A and replace with CYP3A4. Updated summary sentence.