The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H2S metabolism
| Autor: | Sita Arjune, Katalin Erdelyi, Anna-Theresa Mellis, Ye Liang, Tamás Ditrói, Guenter Schwarz, Péter Nagy, Albert L. Misko, Alexander T. Kaczmarek |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry Biochemistry Sulfite oxidase Glutamate oxaloacetate transaminase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Sulfite medicine Citrate synthase Molybdenum cofactor deficiency Sulfite oxidase deficiency lcsh:QH301-705.5 lcsh:R5-920 biology H2S Organic Chemistry Glutathione medicine.disease 030104 developmental biology chemistry lcsh:Biology (General) 6): cysteine catabolism biology.protein sulfide:quinone oxidoreductase Cysteine sulfinic acid Persulfidation lcsh:Medicine (General) 030217 neurology & neurosurgery Cysteine |
| Zdroj: | Redox Biology, Vol 38, Iss, Pp 101800-(2021) |
| ISSN: | 2213-2317 |
| Popis: | 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, H2S and persulfidated cysteine and glutathione, which is consistent with an increase of SQR protein levels. Surprisingly, none of the known H2S-producing pathways were found to be upregulated under conditions of sulfite toxicity suggesting an alternative route of sulfite-induced shift from oxidative to H2S dependent cysteine catabolism. |
| Databáze: | OpenAIRE |
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