The role of system A for neutral amino acid transport in the regulation ofcell volume

System A is a secondary active, sodium dependent transport system for neutr al amino acids. Strictly coupled with Na, K-ATPase, its activity determines the size of the intracellular amino acid pool, through a complex network o f metabolic reaction and exchange fluxes. Many hormones and drugs affect sy stem A activity in specific cell models or tissues. In all the cell models tested thus far the activity of the system is stimulated by amino acid star vation, cell cycle progression, and the incubation under hypertonic conditi ons. These three conditions produce marked alterations of cell volume. The stimulation of system A activity plays an important role in cell volume res toration, through an expansion of the intracellular amino acid pool. Under normal conditions, system A substrates represent a major fraction of cell c ompatible osmolytes, organic compounds that exert a protein stabilizing eff ect. It is, therefore, likely that the activation of system A represents a portion of a more complex response triggered by exposure to stresses of var ious nature. Since system A transporters have been recently cloned, the mol ecular bases of these regulatory mechanisms will probably be elucidated in a short time.