Multi-tasking of biosynthetic and energetic functions of glycolysis explained by supply and demand logic

After more than a century of research on glycolysis, we have detailed descriptions of its molecular organization, but despite this wealth of knowledge, linking the enzyme properties to metabolic pathway behavior remains challenging. These challenges arise from multi-layered regulation and the context and time dependence of component functions. However, when viewed as a system that functions according to the principles of supply and demand, a simplifying theoretical framework can be applied to study its regulation logic and to assess the coherence of experimental interpretations. These principles are universally applicable, as they emphasize the common metabolic tasks of glycolysis: the provision of free-energy carriers, and precursors for biosynthesis and stress-related compounds. Here we will review the regulation of multi-tasking by glycolysis and consider how an understanding of this central metabolic pathway can be pursued using general principles, rather than focusing on the biochemical details of constituent components.