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- W3130342103 abstract "Itaconate is a small molecule metabolite that is endogenously produced by cis-aconitate decarboxylase-1 (ACOD1) in mammalian cells and influences numerous cellular processes. The metabolic consequences of itaconate in cells are diverse and contribute to its regulatory function. Here, we have applied isotope tracing and mass spectrometry approaches to explore how itaconate impacts various metabolic pathways in cultured cells. Itaconate is a competitive and reversible inhibitor of Complex II/succinate dehydrogenase (SDH) that alters tricarboxylic acid (TCA) cycle metabolism leading to succinate accumulation. Upon activation with coenzyme A (CoA), itaconyl-CoA inhibits adenosylcobalamin-mediated methylmalonyl-CoA (MUT) activity and, thus, indirectly impacts branched-chain amino acid (BCAA) metabolism and fatty acid diversity. Itaconate, therefore, alters the balance of CoA species in mitochondria through its impacts on TCA, amino acid, vitamin B12, and CoA metabolism. Our results highlight the diverse metabolic pathways regulated by itaconate and provide a roadmap to link these metabolites to potential downstream biological functions." @default.
- W3130342103 created "2021-03-01" @default.
- W3130342103 creator A5018324826 @default.
- W3130342103 creator A5042375667 @default.
- W3130342103 date "2021-02-18" @default.
- W3130342103 modified "2023-10-18" @default.
- W3130342103 title "Itaconate Alters Succinate and Coenzyme A Metabolism via Inhibition of Mitochondrial Complex II and Methylmalonyl-CoA Mutase" @default.
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- W3130342103 doi "https://doi.org/10.3390/metabo11020117" @default.
- W3130342103 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7922098" @default.
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