The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H 2 S metabolism.

Autor: Mellis AT; Institute for Biochemistry, Department of Chemistry, University of Cologne, Cologne, Germany., Misko AL; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, USA., Arjune S; Institute for Biochemistry, Department of Chemistry, University of Cologne, Cologne, Germany., Liang Y; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, USA., Erdélyi K; Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary., Ditrói T; Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary., Kaczmarek AT; Institute for Biochemistry, Department of Chemistry, University of Cologne, Cologne, Germany., Nagy P; Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary; Department of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary., Schwarz G; Institute for Biochemistry, Department of Chemistry, University of Cologne, Cologne, Germany; Center for Molecular Medicine, University of Cologne, Cologne, Germany. Electronic address: gschwarz@uni-koeln.de.
Jazyk: angličtina
Zdroj: Redox biology [Redox Biol] 2021 Jan; Vol. 38, pp. 101800. Date of Electronic Publication: 2020 Nov 24.
DOI: 10.1016/j.redox.2020.101800
Abstrakt: Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency are two rare genetic disorders that are caused by impairment of the mitochondrial enzyme sulfite oxidase. Sulfite oxidase is catalyzing the terminal reaction of cellular cysteine catabolism, the oxidation of sulfite to sulfate. Absence of sulfite oxidase leads to the accumulation of sulfite, which has been identified as a cellular toxin. However, the molecular pathways leading to the production of sulfite are still not completely understood. In order to identify novel treatment options for both disorders, the understanding of cellular cysteine catabolism - and its alterations upon loss of sulfite oxidase - is of utmost importance. Here we applied a new detection method of sulfite in cellular extracts to dissect the contribution of cytosolic and mitochondrial glutamate oxaloacetate transaminase (GOT) in the transformation of cysteine sulfinic acid to sulfite and pyruvate. We found that the cytosolic isoform GOT1 is primarily responsible for the production of sulfite. Moreover, loss of sulfite oxidase activity results in the accumulation of sulfite, H 2 S and persulfidated cysteine and glutathione, which is consistent with an increase of SQR protein levels. Surprisingly, none of the known H 2 S-producing pathways were found to be upregulated under conditions of sulfite toxicity suggesting an alternative route of sulfite-induced shift from oxidative to H 2 S dependent cysteine catabolism.
(Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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