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Formate induces a metabolic switch in nucleotide and energy metabolism
- Source :
- Cell Death & Disease, Cell Death and Disease, Vol 11, Iss 5, Pp 1-14 (2020), SSRN Electronic Journal
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
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 intraperitoneal injection of formate. We conclude that formate is a potent regulator of purine, pyrimidine and energy metabolism.
- Subjects :
- Purine
Cancer Research
Formates
Argininosuccinate synthase
chemistry.chemical_compound
Adenosine Triphosphate
0302 clinical medicine
Adenine nucleotide
Glycolysis
Nucleotide
Purine metabolism
chemistry.chemical_classification
0303 health sciences
biology
lcsh:Cytology
Nucleotides
Cancer metabolism
3. Good health
Biochemistry
030220 oncology & carcinogenesis
Urea cycle
Pyrimidine metabolism
Female
Colorectal Neoplasms
Pyrimidine
Immunology
education
Models, Biological
Article
Cellular and Molecular Neuroscience
03 medical and health sciences
Cell Line, Tumor
Metabolomics
Animals
Humans
Formate
lcsh:QH573-671
030304 developmental biology
Orotic Acid
Models, Genetic
Adenylate Kinase
Cell Biology
Ribonucleotides
Aminoimidazole Carboxamide
Mice, Inbred C57BL
De novo synthesis
Disease Models, Animal
Pyrimidines
chemistry
biology.protein
Energy Metabolism
Subjects
Details
- ISSN :
- 20414889
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease, Cell Death and Disease, Vol 11, Iss 5, Pp 1-14 (2020), SSRN Electronic Journal
- Accession number :
- edsair.doi.dedup.....1b0827e2416027cbf35c2ca3dc4bb22f