ArticlePloS one2014
The N-reductive system composed of mitochondrial amidoxime reducing component (mARC), cytochrome b5 (CYB5B) and cytochrome b5 reductase (CYB5R) is regulated by fasting and high fat diet in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Sex- and mouse strain-related differences in body weight gain, composition of the gut microbiota, and levels of selected metabolites in response to a Western-style diet.BMC gastroenterology · 2026Article
- Loss of Mtarc1 Protects Against Steatotic Liver Disease in Mice.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Integrated transcriptomic and immune analysis reveals distinct mitochondrial and immune signature in COVID-19 ARDS requiring invasive mechanical ventilation.Frontiers in medicine · 2026Article
- Divergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse.PLoS genetics · 2024Article
- Hepatocyte mARC1 promotes fatty liver disease.JHEP reports : innovation in hepatology · 2023Article
- Association ofInternational journal of molecular sciences · 2022Article
- Interindividual Variability and Differential Tissue Abundance of Mitochondrial Amidoxime Reducing Component Enzymes in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- A genome-first approach to mortality and metabolic phenotypes inMed (New York, N.Y.) · 2021Article
- Therapeutic Targeting of Nonalcoholic Fatty Liver Disease by Downregulating SREBP-1C ExpressionFrontiers in molecular biosciences · 2021Article
- Article
- Mitochondrial amidoxime-reducing component 2 (MARC2) has a significant role inThe Journal of biological chemistry · 2019Article
- Study of Different Variants of Mo Enzyme crARC and the Interaction with Its Partners crCytb5-R and crCytb5-1.International journal of molecular sciences · 2017Article
- Ramadan Fasting and Patients with Cancer: State-of-the-Art and Future Prospects.Frontiers in oncology · 2016Review
- The pivotal role of the mitochondrial amidoxime reducing component 2 in protecting human cells against apoptotic effects of the base analog N6-hydroxylaminopurine.The Journal of biological chemistry · 2015Article
- The mammalian molybdenum enzymes of mARC.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015Review
- Expression and Function of mARC: Roles in Lipogenesis and Metabolic Activation of Ximelagatran.PloS one · 2015Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitochondrial amidoxime reducing component mARC is the fourth mammalian molybdenum enzyme. The protein is capable of reducing N-oxygenated structures, but requires cytochrome b5 and cytochrome b5 reductase for electron transfer to catalyze such reactions. It is well accepted that the enzyme is involved in N-reductive drug metabolism such as the activation of amidoxime prodrugs. However, the endogenous function of the protein is not fully understood. Among other functions, an involvement in lipogenesis is discussed. To study the potential involvement of the protein in energy metabolism, we tested whether the mARC protein and its partners are regulated due to fasting and high fat diet in mice. We used qRT-PCR for expression studies, Western Blot analysis to study protein levels and an N-reductive biotransformation assay to gain activity data. Indeed all proteins of the N-reductive system are regulated by fasting and its activity decreases. To study the potential impact of these changes on prodrug activation in vivo, another mice experiment was conducted. Model compound benzamidoxime was injected to mice that underwent fasting and the resulting metabolite of the N-reductive reaction, benzamidine, was determined. Albeit altered in vitro activity, no changes in the metabolite concentration in vivo were detectable and we can dispel concerns that fasting alters prodrug activation in animal models. With respect to high fat diet, changes in the mARC proteins occur that result in increased N-reductive activity. With this study we provide further evidence that the endogenous function of the mARC protein is linked with lipid metabolism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.