Document Detail

Oxidative metabolism of seleno-L-methionine to L-methionine selenoxide by flavin-containing monooxygenases.
MedLine Citation:
PMID:  17173378     Owner:  NLM     Status:  MEDLINE    
The roles of flavin-containing monooxygenases (FMOs) in the oxidation of seleno-l-methionine (SeMet) to l-methionine selenoxide (MetSeO) were investigated using cDNA-expressed human FMOs, purified rat liver FMOs, and rat liver microsomes. MetSeO and the N-2,4-dinitrophenyl-derivatives of SeMet and MetSeO were synthesized and characterized by 1H-NMR and ESI/MS. These reference compounds were then used to develop a sensitive HPLC assay to monitor SeMet oxidation to MetSeO. The formation of MetSeO in rat liver microsomes was time-, protein concentration-, SeMet concentration-, and NADPH-dependent. The microsomal activity exhibited a SeMet Km value (mean +/- S.D.; n = 4) of 0.91 +/- 0.29 mM and a Vmax value of 44 +/- 8.0 nmol MetSeO/mg protein/min. The inclusion of 1-benzylimidazole, superoxide dismutase, or deferoxamine caused no inhibition of the rat liver microsomal activity. Because these results suggested the involvement of FMOs in the oxidation of SeMet in rat liver microsomes, the formation of MetSeO was also examined using cDNA-expressed human and purified rat FMOs. The results showed that both rat and human FMO1 and FMO3 but not FMO5 can catalyze the reaction. The SeMet kinetic constants were obtained with purified rat liver FMO3 (Km = 0.11 mM, Vmax = 280 nmol/mg protein/min) and rat liver FMO1 (Km = 7.8 mM, Vmax = 1200 nmol/mg protein/min). Because SeMet has anti-cancer, chemopreventive, and toxic properties, the kinetic results suggest that FMO3 is likely to play a role in the biological activities of SeMet at low exposure conditions.
Renee J Krause; Steven C Glocke; Anna Rita Sicuri; Sharon L Ripp; Adnan A Elfarra
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Chemical research in toxicology     Volume:  19     ISSN:  0893-228X     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-18     Completed Date:  2007-03-09     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1643-9     Citation Subset:  IM    
Department of Comparative Biosciences, Center for Molecular and Environmental Toxicology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
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MeSH Terms
Chromatography, High Pressure Liquid
DNA, Complementary / genetics
Dinitrobenzenes / chemistry
Magnetic Resonance Spectroscopy
Metabolic Detoxication, Phase I
Methionine / analogs & derivatives*,  chemistry,  metabolism
Microsomes, Liver / enzymology,  metabolism*
Organoselenium Compounds / chemistry,  metabolism*
Oxygenases / genetics,  metabolism*
Selenomethionine / chemistry,  metabolism*
Spectrometry, Mass, Electrospray Ionization
Grant Support
DK44295/DK/NIDDK NIH HHS; R01 DK044295-08/DK/NIDDK NIH HHS; R01 DK044295-08S1/DK/NIDDK NIH HHS; R01 DK044295-09A2/DK/NIDDK NIH HHS; R01 DK044295-10/DK/NIDDK NIH HHS
Reg. No./Substance:
0/DNA, Complementary; 0/Dinitrobenzenes; 0/Organoselenium Compounds; 0/methionine selenoxide; 1464-42-2/Selenomethionine; 63-68-3/Methionine; EC 1.13.-/Oxygenases; EC monooxygenase (N-oxide forming)

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