RGD Reference Report - Oxidative metabolism of seleno-L-methionine to L-methionine selenoxide by flavin-containing monooxygenases. - Rat Genome Database

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Oxidative metabolism of seleno-L-methionine to L-methionine selenoxide by flavin-containing monooxygenases.

Authors: Krause, RJ  Glocke, SC  Sicuri, AR  Ripp, SL  Elfarra, AA 
Citation: Krause RJ, etal., Chem Res Toxicol. 2006 Dec;19(12):1643-9.
RGD ID: 1626480
Pubmed: PMID:17173378   (View Abstract at PubMed)
PMCID: PMC2533529   (View Article at PubMed Central)
DOI: DOI:10.1021/tx0601915   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
xenobiotic metabolic process  IDA 1626480 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
amino acid binding  IPIPubChem_Compound:1050241626480 RGD 
N,N-dimethylaniline monooxygenase activity  IDA 1626480using alternative substrate L-selenomethionine and see EC 1.14.13.8RGD 
NADP binding  IPINADPH1626480 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fmo3  (flavin containing dimethylaniline monoxygenase 3)


Additional Information