The importance of post-translational modifications in regulating Saccharomyces cerevisiae metabolism

Regulation of the flow of mass and energy through cellular metabolic networks is fundamental to the operation of all living organisms. Such metabolic fluxes are determined by the concentration of limiting substrates and by the amount and kinetic properties of the enzymes. Regulation of the amount of enzyme can be exerted, on a long-term scale, at the level of gene and protein expression. Enzyme regulation by post-translational modifications (PTMs) and noncovalent binding of allosteric effectors are shorter-term mechanisms that modulate enzyme activity. PTMs, in particular protein phosphorylation, are increasingly being recognized as key regulators in many cellular processes, including metabolism. For example, about half of the enzymes in the Saccharomyces cerevisiae metabolic network have been detected as phosphoproteins, although functional relevance has been demonstrated only in a few cases. Direct regulation of enzymes by PTMs provides one of the fastest ways for cells to adjust to environmental cues and internal stimulus. This review charts the so far identified metabolic enzymes undergoing reversible PTMs in the model eukaryote S. cerevisiae and reviews their underlying mechanistic principles both at the individual enzyme level and in the context of the entire metabolic network operation.