Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16α-hydroxylation of 17β-estradiol

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Abstract

The steady-state kinetics and specific activity of 2-, 4-, and 16α-hydroxylation of 17β-estradiol (E2) 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 16α-hydroxylation reaction was catalyzed mainly by CYP1A2 and, to a similar, slightly lower extent, CYP3A4 and 1A1, with a lesser contribution by CYP1B1. The E2 2-, 4-, and 16α-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 E2 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.

Original languageEnglish (US)
Pages (from-to)1001-1003
Number of pages3
JournalMetabolism: Clinical and Experimental
Volume50
Issue number9
DOIs
StatePublished - Jan 1 2001

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Cytochrome P-450 CYP1A2
Hydroxylation
Estradiol
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP3A
Liver
Liver Microsomes
Human Activities
Cytochrome P-450 Enzyme System
Protein Isoforms
Carcinogenesis
Complementary DNA
Enzymes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

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title = "Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16α-hydroxylation of 17β-estradiol",
abstract = "The steady-state kinetics and specific activity of 2-, 4-, and 16α-hydroxylation of 17β-estradiol (E2) 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 16α-hydroxylation reaction was catalyzed mainly by CYP1A2 and, to a similar, slightly lower extent, CYP3A4 and 1A1, with a lesser contribution by CYP1B1. The E2 2-, 4-, and 16α-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 E2 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.",
author = "Badawi, {A. F.} and Ercole Cavalieri and Rogan, {Eleanor G}",
year = "2001",
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T1 - Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16α-hydroxylation of 17β-estradiol

AU - Badawi, A. F.

AU - Cavalieri, Ercole

AU - Rogan, Eleanor G

PY - 2001/1/1

Y1 - 2001/1/1

N2 - The steady-state kinetics and specific activity of 2-, 4-, and 16α-hydroxylation of 17β-estradiol (E2) 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 16α-hydroxylation reaction was catalyzed mainly by CYP1A2 and, to a similar, slightly lower extent, CYP3A4 and 1A1, with a lesser contribution by CYP1B1. The E2 2-, 4-, and 16α-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 E2 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.

AB - The steady-state kinetics and specific activity of 2-, 4-, and 16α-hydroxylation of 17β-estradiol (E2) 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 16α-hydroxylation reaction was catalyzed mainly by CYP1A2 and, to a similar, slightly lower extent, CYP3A4 and 1A1, with a lesser contribution by CYP1B1. The E2 2-, 4-, and 16α-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 E2 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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