Mitochondrial amidoxime reducing component (mARC)

The mitochondrial amidoxime reducing component (mARC) is a molybdenum-containing enzyme, most recently discovered among eukaryotic molybdoenzymes, present as two paralogs in mammals—mARC1 and mARC2 (encoded by the MTARC1 and MTARC2 genes). mARC localizes to the outer mitochondrial membrane and forms a complex with cytochrome b5 type B and NADH cytochrome b5 reductase. Its primary known function is the reduction of N-hydroxylated substrates, particularly amidoxime derivatives and N-oxides, facilitating activation of selected prodrugs and detoxification of toxic metabolites. mARC is integral to specific drug metabolism pathways and may play roles in cellular nitrogen homeostasis and lipid metabolism. Human genetics studies associate certain MARC1 variants with a decreased risk of liver disease. The enzyme’s physiological functions beyond drug metabolism remain incompletely elucidated, but its conserved role in redox chemistry and drug detoxification is clear.

Other names

mARCmARC1 (mitochondrial amidoxime reducing component 1)mARC2 (mitochondrial amidoxime reducing component 2)MOSC1MOSC2MTARC1MTARC2

Enzymatic reduction of N-hydroxylated functional groups to their parent amines; specifically, activates prodrugs requiring N-reduction for bioactivity Detoxification of toxic N-oxygenated metabolites formed by cytochrome P450 or other monooxygenases