Premium
Evidence for the involvement of flavin‐containing monooxygenase 3 (FMO3) in the in vivo S‐oxidation of L‐methionine in female mice
Author(s) -
Dever Joseph Thomas,
Elfarra Adnan
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a263-b
Subject(s) - in vivo , methionine , monooxygenase , microsome , biochemistry , in vitro , chemistry , medicine , microbiology and biotechnology , endocrinology , biology , enzyme , cytochrome p450 , genetics , amino acid
L‐Methionine (Met) is a substrate for FMO1‐4 in vitro. FMO3, the major isoform expressed in adult human liver, exhibits a much lower Km value for Met than FMO1 or FMO2 and catalyzes the S‐oxidation in a stereoselective manner with L‐methionine‐d‐sulfoxide (Met‐d‐O) being preferentially formed over L‐methionine‐l‐sulfoxide (Met‐l‐O). Because FMO3 is also the major isoform expressed in female mouse liver, female mice were used to investigate the role of FMO3 in Met oxidation in vivo after treatment with Met (400 mg/kg, i.p.). At 15 min post treatment, liver Met‐d‐O and Met‐l‐O levels (76 ± 24.6 and 16.2 ± 9.5 nmoles/g tissue, respectively; means ± SD) were significantly increased over Met‐d‐O and Met‐l‐O control levels (23.1 ± 7.7 and 3.3 ± 4.0 nmoles/g tissue, respectively). The fraction of the MetO present as Met‐d‐O in control (86% of total MetO) and treated animals (84%) was similar to the fraction observed when female mouse liver microsomes were incubated with Met (10 mM) and NADPH (69%). Collectively, these results indicate that FMO3 plays a major role in hepatic MetO formation in vivo. (supported by NIDDK44295 and T32‐ES‐7015).