Flavin-containing monooxygenase isoform specificity for the N-oxidation of tamoxifen determined by product measurement and NADPH oxidation.
The Km value for tamoxifen is 1.2 mM for mouse FMO1 (human FMO1 is not expressed in adults) and 1.4 mM for human FMO3, with no detectable activity being expressed toward tamoxifen by FMO5 from either mouse or human. These data are derived from experiments using 3H-tamoxifen as substrate in which the product, tamoxifen N-oxide, was measured directly. It was not possible to derive meaningful data from the measurement of NADPH consumption because Escherichia coli preparations, in the presence of tamoxifen, regardless of whether the E. coli was expressing an FMO isoform, consumed large amounts of NADPH without the appearance of tamoxifen N-oxide or other discernable product.
Hodgson
E
E
Department of Toxicology, North Carolina State University, Raleigh 27695, USA.
Rose
R L
RL
Cao
Y
Y
Dehal
S S
SS
Kupfer
D
D
D000818:Animals; D004965:Estrogen Antagonists / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism*; D013629:Tamoxifen / Q000378:metabolism*
D004965:Estrogen Antagonists; D007527:Isoenzymes; D013629:Tamoxifen; D009249:NADP; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)