Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Oizel, K; Tait-Mulder, J; Fernandez-de-Cossio-Diaz, J; Pietzke, M; Brunton, H; Lilla, S; Dhayade, S; Athineos, D; Blanco, GR; Sumpton, D; Mackay, GM; Blyth, K; Zanivan, SR; Meiser, J; Vazquez, A.
Formate induces a metabolic switch in nucleotide and energy metabolism.
Cell Death Dis. 2020; 11(5):310
Doi: 10.1038/s41419-020-2523-z
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- Co-Autor*innen der Med Uni Graz
- Rodriguez Blanco Giovanny
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- Abstract:
- Formate is a precursor for the de novo synthesis of purine and deoxythymidine nucleotides. Formate also interacts with energy metabolism by promoting the synthesis of adenine nucleotides. Here we use theoretical modelling together with metabolomics analysis to investigate the link between formate, nucleotide and energy metabolism. We uncover that endogenous or exogenous formate induces a metabolic switch from low to high adenine nucleotide levels, increasing the rate of glycolysis and repressing the AMPK activity. Formate also induces an increase in the pyrimidine precursor orotate and the urea cycle intermediate argininosuccinate, in agreement with the ATP-dependent activities of carbamoyl-phosphate and argininosuccinate synthetase. In vivo data for mouse and human cancers confirms the association between increased formate production, nucleotide and energy metabolism. Finally, the in vitro observations are recapitulated in mice following and intraperitoneal injection of formate. We conclude that formate is a potent regulator of purine, pyrimidine and energy metabolism.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenosine Triphosphate - pharmacology
- Adenylate Kinase - metabolism
- Aminoimidazole Carboxamide - analogs & derivatives, pharmacology
- Animals - administration & dosage
- Cell Line, Tumor - administration & dosage
- Colorectal Neoplasms - metabolism, pathology
- Disease Models, Animal - administration & dosage
- Energy Metabolism - drug effects
- Female - administration & dosage
- Formates - pharmacology
- Humans - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Models, Biological - administration & dosage
- Models, Genetic - administration & dosage
- Nucleotides - metabolism
- Orotic Acid - metabolism
- Pyrimidines - metabolism
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