Hydrodynamic consequences of glycolysis: thermodynamic basis and clinical relevance

Since Warburg's original description of aerobic and anaerobic glycolysis in 1924, the biochemical and molecular bases of glucose metabolism in cells have been characterized. However, its thermodynamic implications have found little attention. Van't Hoff's law of thermodynamics was applied here to describe how glucose metabolism affects intracellular osmotic pressure, hence revealing how glucose metabolism provides cells with osmotic energy as well as chemical energy. Ensuing osmosis-driven movement of free water across membranes affects cell volume and shape, hydration of intracellular components, and interactions of cells with their environment. Comparative analysis of extant data revealed strong evidence for clinically relevant glycolysis-driven effects under hypoxic conditions known to occur in cancer, vascular disease as well as intensive care, including critical and preventable ones affecting treatment effectiveness and thus, clinical outcome. These findings provide the first evidence confirming the existence of glycolysis-driven hydrodynamic effects and suggest that high levels of aerobic and anaerobic glycolysis provide a common biophysical basis in seemingly unrelated medical conditions.