Mechanisms of Glycolysis and Fermentation: A Non-Equilibrium Thermodynamics Perspective

Every single chemical formula of modern models of glycolysis violates two laws of nature. Yet, the formulae of the pioneers who investigated metabolism did not violate the laws of nature. Recently, the well-established models of metabolism have collapsed by re-introducing hydrogen as the energy entity driving biological processes. This review builds on a scientific concept of metabolism by introducing that glycolytically generated energy is either transformed into ATP or drives a biological process. The dynamic production and utilization of lactate (lactate flow non-equilibrium) is introduced as a central ATP-driven process and the first step of biosynthesis. A metabolism model based on non-equilibrium thermodynamics replaces the current understanding that one end product of glycolysis is consumed by mitochondria with two intermediates of the two-cell model of metabolism that are consumed by mitochondria. The pyruvate dehydrogenase complex, consuming pyruvic acid, saves one redox unit (2H) for storage as lipid or glycogen, whereas mitochondrial consumption of lactic acid enhances ATP recovery. An uncounted number of signalling pathways temporarily regulate the distribution of this single redox unit. Glycogenolysis massively impacts the flow non-equilibrium, an event permanently memorized by cells. The two-cell model of metabolism starts to functionally unite fields such as memory formation, obesity, exercise, schizophrenia, cancer, and inflammation by the common denominator: metabolism.