The mitochondrial amidoxime reducing component (mARC): involvement in metabolic reduction of N-oxides, oximes and N-hydroxyamidinohydrazones

ChemMedChem. 2014 Oct;9(10):2381-7. doi: 10.1002/cmdc.201402127. Epub 2014 Jul 8.


The mitochondrial amidoxime reducing component (mARC) is a molybdenum-containing enzyme and capable of reducing N-hydroxylated structures such as amidoxime prodrugs. In this study, we tested the involvement of mARC in the reduction of N-oxides (amitriptyline-N-oxide, nicotinamide-N-oxide), oximes ((E)-/(Z)-2,4,6-trimethylacetophenonoxime) and a N-hydroxyamidinohydrazone (guanoxabenz). All groups are reduced by mARC proteins, and the enzymes are therefore involved in the interconversion of N-oxygenated metabolites originating from cytochrome P450s and flavin-containing monooxygenases. In addition, these structures open up further options for serving as prodrugs. Thus, with respect to these reactions, testing of candidates with N-oxygenated structures should not solely be carried out in microsomal enzyme sources but as well in mitochondria. However, differences in the reduction of oximes and N-oxides between the two isoforms, namely mARC1 and mARC2, were detectable; N-oxides are exclusively reduced by mARC1. We therefore assume differences between the so far unknown 3D structures of the two proteins.

Keywords: Moco sulfurase C-terminal domain/MOSC; metabolism; mitochondrial amidoxime reducing component; nitrogene oxides; oximes.

MeSH terms

  • Hydrazones / chemistry*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxides / pharmacology*
  • Oximes / pharmacology*


  • Hydrazones
  • Oxides
  • Oximes