title: Potential role of the flavin-containing monooxygenases in the metabolism of endogenous compounds.
abstract: Several xenobiotics and their corresponding cysteine S-conjugates are metabolized in vivo to cysteine S-conjugate sulfoxides and/or N-acetylcysteine S-conjugate sulfoxides. Homocysteine S-conjugates, such as methionine and ethionine, are also metabolized in vivo to sulfoxides. The enzymatic basis for these metabolic reactions is not known. Recently, the rat liver and kidney S-benzyl-L-cysteine S-oxidase activities were found to be associated with flavin-containing monooxygenases that are structurally and immunochemically related to known FMO1 isoforms. Further evidence for FMO1 being the major FMO isoform involved in S-benzyl-L-cysteine sulfoxidation was obtained from kinetic studies with cDNA-expressed rabbit FMOs. Endogenous cysteine S-conjugates, e.g. cysteinylcatecholamines, cysteinylleukotrienes, lanthionine and djenkolic acid may also be substrates for FMOs, since S-benzyl-L-cysteine can be considered a model for these compounds. Methionine, an endogenous homocysteine S-conjugate, was shown to be a substrate for cDNA-expressed rabbit FMO1, FMO2, and FMO3, however, the methionine sulfoxidation reaction was preferentially catalyzed by FMO3. These results suggest that FMOs may also play a role in the in vivo metabolism of endogenous homocysteine S-conjugates.
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin School of Veterinary Medicine, Madison 53706-1102, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Elfarra
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D008322:Mammals; D008715:Methionine / Q000378:metabolism*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism* / Q000502:physiology; D013454:Sulfoxides / Q000737:chemistry / Q000378:metabolism
chemical_list: D013454:Sulfoxides; D006710:Homocysteine; C002206:S-benzylcysteine; D008715:Methionine; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine