Kynurenine aminotransferase activity of Aro8/Aro9 engage tryptophan degradation by producing kynurenic acid in Saccharomyces cerevisiae
| Autor: | Kazuto Ohashi, Satoshi Yoshida, Craig E. Wheelock, Masak Takaine, Romanas Chaleckis |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Metabolite Mutant Deamination lcsh:Medicine Saccharomyces cerevisiae Biology Kynurenic Acid Article 03 medical and health sciences chemistry.chemical_compound Kynurenic acid Kynurenine aminotransferase activity lcsh:Science Transaminases chemistry.chemical_classification Multidisciplinary lcsh:R Tryptophan Amino acid 030104 developmental biology chemistry Biochemistry Mutagenesis Mutation lcsh:Q Kynurenine |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-12392-6 |
| Popis: | Kynurenic acid (KA) is a tryptophan (Trp) metabolite that is synthesised in a branch of kynurenine (KYN) pathway. KYN aminotransferase (KAT) catalyses deamination of KYN, yielding KA. Although KA synthesis is evolutionarily conserved from bacteria to humans, the cellular benefits of synthesising KA are unclear. In this study, we constructed a KAT-null yeast mutant defective in KA synthesis to clarify the cellular function of KA. Amino acid sequence analysis and LC/MS quantification of KA revealed that Aro8 and Aro9 are the major KATs. KA was significantly decreased in the aro8Δ aro9Δ double mutant. We found that aro8Δ aro9Δ cells did not exhibit obvious defects in growth or oxidative stress response when proper amounts of amino acids are supplied in the media. We further found that aro8Δ aro9Δ cells were sensitive to excess Trp. The Trp sensitivity was not rescued by addition of KA, suggesting that Trp sensitivity is not due to the loss of KA. In conclusion, we propose that KAT activity is required for detoxification of Trp by converting it to the less toxic KA. |
| Databáze: | OpenAIRE |
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