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Hudert, Christian; Mann, Jake

doi:10.1002/hep4.2009

Cited by 2 publications

(1 citation statement)

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“…The mutated residue A165 is some 25 Å away from the active site of mARC1, and despite some in silico studies suggesting that the variant protein would “cause loss of the alpha-helix and alter the metal-binding ability of MTARC1” as well as “affect the overall stability of the protein” [ 100 ], our own X-ray crystallographic analysis of the variant protein revealed no structural differences between the wild type and variant [ 101 ]. The mechanism by which the mARC1 p.A165T variant influences liver disease remains unknown, and it might require significant efforts to understand it [ 102 ].…”

Section: Marc Enzymes In Human Diseasementioning

confidence: 99%

The History of mARC

Clement

Struwe

2023

Molecules

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The mitochondrial amidoxime-reducing component (mARC) is the most recently discovered molybdoenzyme in humans after sulfite oxidase, xanthine oxidase and aldehyde oxidase. Here, the timeline of mARC’s discovery is briefly described. The story begins with investigations into N-oxidation of pharmaceutical drugs and model compounds. Many compounds are N-oxidized extensively in vitro, but it turned out that a previously unknown enzyme catalyzes the retroreduction of the N-oxygenated products in vivo. After many years, the molybdoenzyme mARC could finally be isolated and identified in 2006. mARC is an important drug-metabolizing enzyme and N-reduction by mARC has been exploited very successfully for prodrug strategies, that allow oral administration of otherwise poorly bioavailable therapeutic drugs. Recently, it was demonstrated that mARC is a key factor in lipid metabolism and likely involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The exact link between mARC and lipid metabolism is not yet fully understood. Regardless, many now consider mARC a potential drug target for the prevention or treatment of liver diseases. This article focusses on discoveries related to mammalian mARC enzymes. mARC homologues have been studied in algae, plants and bacteria. These will not be discussed extensively here.

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Section: Marc Enzymes In Human Diseasementioning

confidence: 99%