The molybdenum cofactor enzyme mARC: Moonlighting or promiscuous enzyme?
Molybdenum (Mo) is present in the active center of eukaryotic enzymes as a tricyclic pyranopterin chelate compound forming the Mo Cofactor (Moco). Four Moco containing enzymes are known in eukaryotes, nitrate reductase (NR), sulfite oxidase (SO), xanthine oxidoreductase (XOR), and aldehyde oxidase (AO). A fifth Moco enzyme has been recently identified. Because of the ability of this enzyme to convert by reduction several amidoximes prodrugs into their active amino forms, it was named mARC (mitochondrial Amidoxime Reducing Component). This enzyme is also able to catalyze the reduction of a broad range of N-hydroxylated compounds (NHC) as the base analogue 6-hydroxylaminopurine (HAP), as well as nitrite to nitric oxide (NO). All the mARC proteins need reducing power that is supplied by other proteins. The human and plants mARC proteins require a Cytochrome b5 (Cytb5) and a Cytochrome b5 reductase (Cytb5-R) to form an electron transfer chain from NADH to the NHC. Recently, plant mARC proteins were shown to be implicated in the reduction of nitrite to NO, and it was proposed that the electrons required for the reaction were supplied by NR instead of Cytochrome b5 components. This newly characterized mARC activity was termed NO Forming Nitrite Reductase (NOFNiR). Moonlighting proteins form a special class of multifunctional enzymes that can perform more than one function; if the extra function is not physiologically relevant, they are called promiscuous enzymes. In this review, we summarize the current knowledge on the mARC protein, and we propose that mARC is a new moonlighting enzyme. © 2017 BioFactors, 43(4):486-494, 2017.
['Llamas|Angel|A|http://orcid.org/0000-0001-6042-9472', 'Chamizo-Ampudia|Alejandro|A|', 'Tejada-Jimenez|Manuel|M|', 'Galvan|Aurora|A|', 'Fernandez|Emilio|E|']
D042931:Aldehyde Oxidase D000818:Animals D003067:Coenzymes D015786:Cytochromes b5 D006801:Humans D008667:Metalloproteins D000090006:Molybdenum Cofactors D050901:Nitrate Reductase D011621:Pteridines D050876:Sulfite Oxidase D014968:Xanthine Dehydrogenase
molybdenum mARC moonlighting promiscuous NOFNiR