Most processes in cells do not take place independently of one another or at a constant rate. The activities of all proteins and other biomolecules are regulated to integrate their functions for optimal performance for survival. For example, the catalytic activity of enzymes is regulated so that the amount of reaction product is just sufficient to meet the needs of the cell. As a result, the steady-state concentrations of substrates and products may vary depending on cellular conditions. Regulation of nonenzymatic proteins—the opening or closing of membrane channels or the assembly of a macromolecular complex, for example—is also essential.

In general, there are three ways to regulate protein activity. First, cells can increase or decrease the steady-state level of the protein by altering its rate of synthesis, its rate of degradation, or both. Second, cells can change the intrinsic activity, as distinct from the amount, of the protein. For example, through noncovalent and covalent interactions, cells can change the affinity of substrate binding, or the fraction of time the protein is in an active versus an inactive conformation. Third, there can be a change in the location or the concentration within the cell of the protein itself, of the target of the protein’s activity (e.g., an enzyme’s substrate), or of some other molecule required for the protein’s activity (e.g., an enzyme’s cofactor). All three types of regulation play essential roles in the lives and functions of cells. In this section, we first discuss mechanisms for regulating the amount of a protein, then turn to noncovalent and covalent interactions that regulate protein activity.