Abstract
BackgroundIn this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis, whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells. We show that this may result in cancer via mitotic failure, recasting the current conception of the Warburg effect as a metabolic dysregulation consequent to cancer, to a biophysical defect that may contribute to cancer initiation.ModelOur model is based on analogs of thermodynamic concepts that tie non-equilibrium fluid dynamics ultimately to metabolic imbalance, disrupted microtubule dynamics, and finally, genomic instability, from which cancers can arise. Specifically, we discuss how an analog of non-equilibrium Rayleigh-Benard convection can result in glycolytic oscillations and cause a cell to become locked into a higher-entropy state characteristic of cancer.ConclusionsA quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell. Contrary to current understanding, this effect may precipitate cancer development, rather than follow from it, providing new insights into carcinogenesis, cancer treatment, and prevention.
Highlights
In this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis, whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells
A quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell
Given the reaction dynamics afforded by Le Chatelier’s principle, it is possible to imagine that an external concentration of, for example, glucose allowed entry into a cell would ripple through the molecular network of a cell and produce an excess of the appropriate glycolytic enzymes and other molecules associated with anaerobic processing
Summary
Summary We have described an integrated system model for the progression of a healthy cell to a cancer state and some of the implications. The potentially aberrant state of the cell may start by an excess glucose or other nutrient external to the cell impacting the cell or by internal defects leading to metabolic enzyme redistribution processes This excess nutrient is essentially a chemical potential difference between inside and outside of the cell creating stress. We hypothesize that excess of glucose and sugar-like energy sources or metabolic enzyme abnormalities, through a non-equilibrium phase transition (a symmetry breaking phenomenon) analogous to the Rayleigh-Benard convection, may cause a cell to prefer to process this energy source using substrate glycolysis. 3-bromopyruvate may force, via Le Chatelier’s principle, some reverse reactions to essentially deprive the cancer cell of substrate-created ATP. This leaves the cell little choice except to enter apoptosis.
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