The significance of active versus inactive flavin-containing monooxygenase 2 (FMO2) for human drug and xenobiotic metabolism and sensitivity is unknown, but the underlying ethnic polymorphism is well documented. We used quantitative real-time PCR to measure message levels of Fmo1, Fmo2, Fmo3 and Fmo5 in lung and liver from eight strains of 8 week old female mice to determine if a strain could be identified that predominately expressed Fmo2 in lung, recapitulating the human FMO expression profile and being the ideal strain for Fmo2 knockout studies. We also characterized enzyme activity of baculovirus expressed mouse Fmo1, Fmo2 and Fmo3 to identify a substrate or incubation conditions capable of discriminating Fmo2 from Fmo mixtures. Fmo transcript expression patterns were similar for all strains. In lung, 59% of total FMO message was Fmo2, but Fmo1 levels were also high, averaging 34%, whereas Fmo3 and Fmo5 levels were 2 and 5%, respectively. In liver, Fmo1, Fmo2, Fmo3 and Fmo5 contributed 16, 1, 7 and 76% respectively, of detected message. Peak activity varied by isoform and was pH- and substrate-dependent. Fmo3 oxidation of methyl p-tolyl sulfide was negligible at pH 9.5, but Fmo3 oxidation of methimazole was comparable to Fmo1 and Fmo2. Heating microsomes at 50 degrees C for 10min eliminated most Fmo1 and Fmo3 activity, while 94% of Fmo2 activity remained. Measurement of activity in heated and unheated lung and liver microsomes verified relative transcript abundance. Our results show that dual Fmo1/2 knockouts will be required to model the human lung FMO profile.
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http://dx.doi.org/10.1016/j.bcp.2007.09.006 | DOI Listing |
Mol Genet Genomics
December 2024
Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK.
Flavin-containing monooxygenases (FMOs) are present in most organisms including plants, fungi, bacteria, invertebrates and vertebrates, where they catalyse the oxidative metabolism of a range of xenobiotics and endogenous metabolites. FMOs have been associated with ageing and longevity in the mouse and in C. elegans.
View Article and Find Full Text PDFBMC Oral Health
November 2024
Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatology Key lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
J Agric Food Chem
December 2024
College of Plant Protection, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing Agricultural University, Weigang Road 1, Nanjing, Jiangsu 210095, China.
J Clin Invest
October 2024
Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Myocardial infarction (MI) is characterized by massive cardiomyocyte (CM) death and cardiac dysfunction, and effective therapies to achieve cardioprotection are greatly needed. Here, we report that flavin-containing monooxygenase 2 (FMO2) levels were markedly increased in CMs in both ex vivo and in vivo models of ischemic injury. Genetic deletion of FMO2 resulted in reduced CM survival and enhanced cardiac dysfunction, whereas CM-specific FMO2 overexpression conferred a protective effect in infarcted rat hearts.
View Article and Find Full Text PDFChem Res Toxicol
November 2024
Human BioMolecular Research Institute. 6351 Nancy Ridge Road, Suite B, San Diego, California 92121, United States.
Hepatic flavin-containing monooxygenase 3 (FMO3) is arguably the most important FMO in humans from the standpoint of drug metabolism. Recently, adult hepatic FMO3 has been linked to several conditions including cardiometabolic diseases, aging, obesity, and atherosclerosis in small animals. Despite the importance of FMO3 in drug and chemical metabolism, relative to cytochrome P-450 (CYP), fewer studies have been published describing drug and chemical metabolism.
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