Oizel, K. et al. (2020) Formate induces a metabolic switch in nucleotide and energy metabolism. Cell Death and Disease, 11(5), 310. (doi: 10.1038/s41419-020-2523-z) (PMID:32366892) (PMCID:PMC7198490)
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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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Blyth, Professor Karen and Sumpton, Mr David and Lilla, Dr Sergio and Tait-Mulder, Dr Jacqueline and Zanivan, Professor Sara and Vazquez, Alexei and Mackay, Dr Gillian and Athineos, Mr Dimitris |
| Authors: | Oizel, K., Tait-Mulder, J., Fernandez-de-Cossio-Diaz, J., Pietzke, M., Brunton, H., Lilla, S., Dhayade, S., Athineos, D., Blanco, G. R., Sumpton, D., Mackay, G. M., Blyth, K., Zanivan, S. R., Meiser, J., and Vazquez, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Cell Death and Disease |
| Publisher: | Nature Publishing Group |
| ISSN: | 2041-4889 |
| ISSN (Online): | 2041-4889 |
| Copyright Holders: | Copyright © The Author(s) 2020 |
| First Published: | First published in Cell Death and Disease 11:310 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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