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Reduction of Hydrogen Peroxide by Human Mitochondrial Amidoxime Reducing Component Enzymes

ORCID
0000-0002-8793-9971
Affiliation
Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Kiel University, 24118 Kiel, Germany;(S.R.);(P.M.I.);(M.A.S.);(C.K.);(T.K.)
Rixen, Sophia;
Affiliation
Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Kiel University, 24118 Kiel, Germany;(S.R.);(P.M.I.);(M.A.S.);(C.K.);(T.K.)
Indorf, Patrick M.;
Affiliation
Department of Structural Biology, Zoological Institute, Kiel University, 24118 Kiel, Germany;(C.K.);(A.J.S.)
Kubitza, Christian;
ORCID
0000-0001-6931-1841
Affiliation
Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Kiel University, 24118 Kiel, Germany;(S.R.);(P.M.I.);(M.A.S.);(C.K.);(T.K.)
Struwe, Michel A.;
ORCID
0000-0001-6574-2986
Affiliation
Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Kiel University, 24118 Kiel, Germany;(S.R.);(P.M.I.);(M.A.S.);(C.K.);(T.K.)
Klopp, Cathrin;
ORCID
0000-0002-2382-8818
Affiliation
Department of Structural Biology, Zoological Institute, Kiel University, 24118 Kiel, Germany;(C.K.);(A.J.S.)
Scheidig, Axel J.;
Affiliation
Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Kiel University, 24118 Kiel, Germany;(S.R.);(P.M.I.);(M.A.S.);(C.K.);(T.K.)
Kunze, Thomas;
Affiliation
Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Kiel University, 24118 Kiel, Germany;(S.R.);(P.M.I.);(M.A.S.);(C.K.);(T.K.)
Clement, Bernd

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 (H 2 O 2 ) by the human mARC1 and mARC2 enzymes. Furthermore, we demonstrate an increased sensitivity toward H 2 O 2 for HEK-293T cells with an MTARC1 knockout, which implies a role of mARC enzymes in the cellular response to oxidative stress. H 2 O 2 is a reactive oxygen species (ROS) formed in all living cells involved in many physiological processes. Furthermore, H 2 O 2 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.

Category

Editor:
Osella, Domenico
Published in:
Molecules  
Vol. 28, No. 17 (31.08.2023)
Volume:
28
No.:
17
Date Issued:
31.08.2023
DOI:
10.3390/molecules28176384
Language:
English
Type of Resource:
Text
Keywords:
reactive oxygen species; hydrogen peroxide; molybdenum enzyme
Subject of DNB:
610 Medical sciences Medicine
DDC:
615 Pharmakologie, Therapie

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