TY - JOUR
T1 - Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16α-hydroxylation of 17β-estradiol
AU - Badawi, Alaa F.
AU - Cavalieri, Ercole L.
AU - Rogan, Eleanor G.
N1 - Funding Information:
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE. Submitted November 10, 2000; accepted March 23, 2001. Supported by US Public Health Service grants PO1 CA49210 and RO1 CA49917 from the National Cancer Institute. Core support to the Eppley Institute was provided by grant CA 36727 from the National Cancer Institute. Address reprint requests to Alaa F. Badawi, PhD, Eppley Institute for Research in Cancer, 986805 University of Nebraska Medical Center, Omaha, NE 68198-6805. E-mail: [email protected]. Copyright © 2001 by W.B. Saunders Company 0026-0495/01/5009-0003$35.00/0 doi:10.1053/meta.2001.25592
PY - 2001
Y1 - 2001
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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U2 - 10.1053/meta.2001.25592
DO - 10.1053/meta.2001.25592
M3 - Article
C2 - 11555828
AN - SCOPUS:0034800442
SN - 0026-0495
VL - 50
SP - 1001
EP - 1003
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 9
ER -