How did glycogen structure evolve to satisfy the requirement for rapid mobilization of glucose? A problem of physical constraints in structure building.

Optimization of molecular design in cellular metabolism is a necessary condition for guaranteeing a good structure-function relationship. We have studied this feature in the design of glycogen by means of the mathematical model previously presented that describes glycogen structure and its optimization function [Meléndez-Hevia et al. (1993), Biochem J 295: 477-483]. Our results demonstrate that the structure of cellular glycogen is in good agreement with these principles. Because the stored glucose in glycogen must be ready to be used at any phase of its synthesis or degradation, the full optimization of glycogen structure must also imply the optimization of every intermediate stage in its formation. This case can be viewed as a molecular instance of the eye problem, a classical paradigm of natural selection which states that every step in the evolutionary formation of a functional structure must be functional. The glycogen molecule has a highly optimized structure for its metabolic function, but the optimization of the full molecule has meaning and can be understood only by taking into account the optimization of each intermediate stage in its formation.