The fourth mammalian molybdenum enzyme mARC: current state of research

Drug Metab Rev. 2011 Nov;43(4):524-39. doi: 10.3109/03602532.2011.608682. Epub 2011 Sep 26.

Abstract

The mitochondrial amidoxime-reducing component (mARC) is a recently discovered molybdenum-containing enzyme in mammalians. Upon reconstitution with the electron transport proteins, cytochrome b(5) and its reductase, this molybdenum enzyme is capable of reducing N-hydroxylated compounds. It was named mARC because the N-reduction of amidoxime structures was initially studied using this isolated mitochondrial enzyme. All hitherto analyzed mammalian genomes harbor two mARC genes: molybdenum cofactor (Moco) sulferase C-terminal domain MOSC1 and MOSC2. Proteins encoded by these genes represent the simplest eukaryotic molybdenum enzymes, in that they bind only the Moco. It is also suggested that they are members of a new family of molybdenum enzymes. mARC and its N-reductive enzyme system plays a major role in drug metabolism, especially in the activation of so-called "amidoxime-prodrugs" and in the detoxification of N-hydroxylated xenobiotics, though its physiological relevance is largely unknown.

Publication types

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

MeSH terms

  • Animals
  • Biotransformation
  • Coenzymes / metabolism
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Metalloproteins / metabolism
  • Mitochondria / enzymology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molybdenum Cofactors
  • Oxidation-Reduction
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Prodrugs / metabolism
  • Pteridines / metabolism
  • Substrate Specificity

Substances

  • Coenzymes
  • Metalloproteins
  • Mitochondrial Proteins
  • Molybdenum Cofactors
  • Prodrugs
  • Pteridines
  • molybdenum cofactor
  • Oxidoreductases
  • amidoxime reducing component, human
  • mitochondrial amidoxime reducing component 1, human
  • mitochondrial amidoxime reducing component 2, human