Potential role of the flavin-containing monooxygenases in the metabolism of endogenous compounds

Chem Biol Interact. 1995 Apr 28;96(1):47-55. doi: 10.1016/0009-2797(94)03582-s.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acetylcysteine / metabolism
  • Animals
  • Cysteine / analogs & derivatives*
  • Cysteine / metabolism
  • Glutathione / metabolism
  • Homocysteine / metabolism
  • Mammals
  • Methionine / metabolism*
  • Oxidation-Reduction
  • Oxygenases / metabolism*
  • Oxygenases / physiology
  • Sulfoxides / chemistry
  • Sulfoxides / metabolism

Substances

  • Sulfoxides
  • Homocysteine
  • S-benzylcysteine
  • Methionine
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)
  • Glutathione
  • Cysteine
  • Acetylcysteine