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Published on: February 24, 2018
Reduction of Hydrogen Peroxide by Human Mitochondrial Amidoxime Reducing Component Enzymes
Sophia Rixen1, Patrick M Indorf1, Christian Kubitza2
1Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Kiel University, 24118 Kiel, Germany.
Abstract:
The mitochondrial amidoxime reducing component (mARC) is a human molybdoenzyme known to catalyze the reduction of various N-oxygenated substrates. The physiological function of mARC enzymes, however, remains unknown. In this study, we examine the reduction of hydrogen peroxide (H2O2) by the human mARC1 and mARC2 enzymes. Furthermore, we demonstrate an increased sensitivity toward H2O2 for HEK-293T cells with an MTARC1 knockout, which implies a role of mARC enzymes in the cellular response to oxidative stress. H2O2 is a reactive oxygen species (ROS) formed in all living cells involved in many physiological processes. Furthermore, H2O2 constitutes the first mARC substrate without a nitrogen-oxygen bond, implying that mARC enzymes may have a substrate spectrum going beyond the previously examined N-oxygenated compounds.
Insights
The human mitochondrial amidoxime reducing component (mARC) enzymes may play a role in cellular oxidative stress response. This study shows mARC enzymes reduce hydrogen peroxide (H2O2), a reactive oxygen species.
Area of Science:
- Biochemistry
- Cellular Biology
- Enzymology
Background:
- The mitochondrial amidoxime reducing component (mARC) is a human molybdoenzyme.
- mARC enzymes are known to catalyze the reduction of N-oxygenated substrates.
- The physiological function of mARC enzymes remains largely unknown.
Purpose of the Study:
- To investigate the reduction of hydrogen peroxide (H2O2) by human mARC1 and mARC2 enzymes.
- To explore the role of mARC enzymes in the cellular response to oxidative stress.
Main Methods:
- Enzymatic assays to study H2O2 reduction by mARC1 and mARC2.
- Generation and analysis of HEK-293T cells with an MTARC1 knockout.
Main Results:
- Human mARC1 and mARC2 enzymes were shown to reduce H2O2.
- HEK-293T cells with MTARC1 knockout exhibited increased sensitivity to H2O2.
- H2O2 was identified as the first mARC substrate lacking a nitrogen-oxygen bond.
Conclusions:
- mARC enzymes are implicated in the cellular response to oxidative stress.
- The substrate spectrum of mARC enzymes may extend beyond N-oxygenated compounds to include molecules like H2O2.
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