Molecular Crowding and Metabolism in Cells
Author Information
Author(s): Alexei Vazquez, Zoltán N. Oltvai
Primary Institution: Robert Wood Johnson Medical School and The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey
Hypothesis
Is there a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology?
Conclusion
Intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating and non-proliferating cells with high metabolic demand.
Supporting Evidence
- The Warburg effect is a metabolic phenotype displayed by most cancer cells.
- Aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles.
- The model predicts that the lactate switch in proliferating cells is accompanied by activation of glutaminolysis.
Takeaway
Cells need energy to grow and move, and they sometimes use a less efficient way to make energy when they need it fast. This study shows that how crowded the inside of a cell is can change how it makes energy.
Methodology
The study developed a model of human central metabolism that incorporates solvent capacity constraints of metabolic enzymes and mitochondria.
Limitations
The model is based on a steady state approximation and cannot account for short-term events.
Digital Object Identifier (DOI)
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