ArticlePloS one2018
Modelling the impact of changes in the extracellular environment on the cytosolic free NAD+/NADH ratio during cell culture.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- The return of metabolism: biochemistry and physiology of glycolysis.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Effects of L-cysteine on the synthesis and secretion of extracellular pigments in submerged fermentation ofFrontiers in microbiology · 2026Article
- 2,4-Dinitrophenol is toxic on a low caloric diet but extends lifespan of Drosophila melanogaster on nutrient-rich diets without an impact on metabolism.Biogerontology · 2024Article
- The synergism of cytosolic acidosis and reduced NADJournal of biomedical science · 2024Article
- Monitoring and modelling the dynamics of the cellular glycolysis pathway: A review and future perspectives.Molecular metabolism · 2022Review
- Global changes to HepG2 cell metabolism in response to galactose treatment.American journal of physiology. Cell physiology · 2021Article
- Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of CaFrontiers in cell and developmental biology · 2020Article
- Modelling the effects of glucagon during glucose tolerance testing.Theoretical biology & medical modelling · 2019Article
- Calmodulin Is the Fundamental Regulator of NADK-Mediated NAD Signaling in Plants.Frontiers in plant science · 2019Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Cancer cells depend on glucose metabolism via glycolysis as a primary energy source, despite the presence of oxygen and fully functioning mitochondria, in order to promote growth, proliferation and longevity. Glycolysis relies upon NAD+ to accept electrons in the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) reaction, linking the redox state of the cytosolic NAD+ pool to glycolytic rate. The free cytosolic NAD+/NADH ratio is involved in over 700 oxidoreductive enzymatic reactions and as such, the NAD+/NADH ratio is regarded as a metabolic readout of overall cellular redox state. Many experimental techniques that monitor or measure total NAD+ and NADH are unable to distinguish between protein-bound and unbound forms. Yet total NAD+/NADH measurements yield little information, since it is the free forms of NAD+ and NADH that determine the kinetic and thermodynamic influence of redox potential on glycolytic rate. Indirect estimations of free NAD+/NADH are based on the lactate/pyruvate (L/P) ratio at chemical equilibrium, but these measurements are often undermined by high lability. To elucidate the sensitivity of the free NAD+/NADH ratio to changes in extracellular substrate, an in silico model of hepatocarcinoma glycolysis was constructed and validated against in vitro data. Model simulations reveal that over experimentally relevant concentrations, changes in extracellular glucose and lactate concentration during routine cancer cell culture can lead to significant deviations in the NAD+/NADH ratio. Based on the principles of chemical equilibrium, the model provides a platform from which experimentally challenging situations may be examined, suggesting that extracellular substrates play an important role in cellular redox and bioenergetic homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.