title: The mammalian molybdenum enzymes of mARC.
abstract: The "mitochondrial amidoxime reducing component" (mARC) is the most recently discovered molybdenum-containing enzyme in mammals. All mammalian genomes studied to date contain two mARC genes: MARC1 and MARC2. The proteins encoded by these genes are mARC-1 and mARC-2 and represent the simplest form of eukaryotic molybdenum enzymes, only binding the molybdenum cofactor. In the presence of NADH, mARC proteins exert N-reductive activity together with the two electron transport proteins cytochrome b5 type B and NADH cytochrome b5 reductase. This enzyme system is capable of reducing a great variety of N-hydroxylated substrates. It plays a decisive role in the activation of prodrugs containing an amidoxime structure, and in detoxification pathways, e.g., of N-hydroxylated purine and pyrimidine bases. It belongs to a group of drug metabolism enzymes, in particular as a counterpart of P450 formed N-oxygenated metabolites. Its physiological relevance, on the other hand, is largely unknown. The aim of this article is to summarize our current knowledge of these proteins with a special focus on the mammalian enzymes and their N-reductive activity.
authors.affiliation: Institute of Pharmacy, Christian-Albrechts-University of Kiel, Gutenbergstraße 76, 24118, Kiel, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Ott
authors.forename: Antje
authors.initials: A
authors.lastname: Havemeyer
authors.forename: Bernd
authors.initials: B
authors.lastname: Clement
mesh_terms: D000818:Animals; D003067:Coenzymes / Q000737:chemistry*; D015786:Cytochromes b5 / Q000737:chemistry / Q000378:metabolism; D004579:Electron Transport; D006801:Humans; D008322:Mammals; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D050216:Metabolic Detoxication, Phase I; D008667:Metalloproteins / Q000737:chemistry*; D008928:Mitochondria / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism; D008982:Molybdenum / Q000737:chemistry* / Q000378:metabolism; D000090006:Molybdenum Cofactors; D009243:NAD / Q000737:chemistry; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D011621:Pteridines / Q000737:chemistry*
chemical_list: D003067:Coenzymes; D015786:Cytochromes b5; D008565:Membrane Proteins; D008667:Metalloproteins; D024101:Mitochondrial Proteins; D008982:Molybdenum; D000090006:Molybdenum Cofactors; D009243:NAD; D010088:Oxidoreductases; D011621:Pteridines; C022261:molybdopterin; C570001:MTARC2 protein, human; C534493:amidoxime reducing component, human