Cited by 185Pharmacogenetics and Drug MetabolismEstrogen and related hormone effectsMetal-Catalyzed Oxygenation Mechanisms

Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16[alpha ]-hydroxylation of 17[beta ]-estradiol

Badawi, Alaa F., Cavalieri, Ercole L., Rogan, Eleanor G.·2001·Metabolism

Abstract

The steady-state kinetics and specific activity of 2-, 4-, and 16alpha-hydroxylation of 17beta-estradiol (E(2)) were evaluated for human cytochrome P450 (CYP) 1A1, 1A2, 1B1, and 3A4 enzymes, using complementary DNA-expressed CYP isoforms. CYP1A2 showed the highest 2-hydroxylation activity, followed by CYP1A1, 1B1, and 3A4. CYP1B1 had the highest 4-hydroxylation activity, followed by CYP1A2, 1A1, and 3A4. The 16alpha-hydroxylation reaction was catalyzed mainly by CYP1A2 and, to a similar, slightly lower extent, CYP3A4 and 1A1, with a lesser contribution by CYP1B1. The E(2) 2-, 4-, and 16alpha-hydroxylation activities of human liver microsomes were 1.3 +/- 0.3, 0.5 +/- 0.06, and 0.3 +/- 0.05 nmol metabolite/min/nmol P450, respectively. The contribution of CYP1A1 and 1B1 (mainly extrahepatic) to the E(2) hydroxylation reactions, relative to CYP1A2 and 3A4 (predominantly hepatic), may be relevant to understanding the process of hormonal carcinogenesis both in liver and in extrahepatic tissues.

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Crossref · 10.1053/meta.2001.25592

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Authors
Badawi, A. F., Cavalieri, E. L., & Rogan, E. G.
Affiliations
University of Nebraska Medical Center (US)
Venue
Metabolism
Publisher
Elsevier BV
Published
2001-09
Volume
50
Issue
9
Pages
1001-1003
ISSN
0026-0495 (ISSN-L)
OpenAlex
W2087962059
Cited by
184
References
15
Citations by year
2026: 2 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 11 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 9 · 2013: 9 · 2012: 8
FWCI
5.14
Type
journal article
Language
en
Open access
closed
Locations
  • Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ca049917-11)
  • National Cancer Institute (P01CA049210, R01CA49917, P01CA 49210, CA-36727, P30CA036727)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
Keywords
estradiol, cytochrome P450, CYP1A2, CYP1A1, CYP1B1, CYP3A4, 2-hydroxylation, 4-hydroxylation, 16α-hydroxylation, estradiol metabolism, steady-state kinetics, liver microsomes, extrahepatic metabolism, hormonal carcinogenesis
MeSH terms
Aryl Hydrocarbon Hydroxylases, Cytochrome P-450 Enzyme System, Estradiol, Humans, Mixed Function Oxygenases, Hydroxylation, Isoenzymes, Kinetics, Microsomes, Liver, Recombinant Proteins, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A2, Steroid 16-alpha-Hydroxylase, Cytochrome P-450 CYP3A, Cytochrome P-450 CYP1B1, Cytochrome P-450 CYP2C8, Cytochrome P-450 CYP2C9

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