Sodium-dependent Neutral Amino Acid Transporters (SNATs) 1−11 (SLC38A1−11) are transmembrane proteins that mediate the cellular uptake of neutral amino acids in sodium- and pH-dependent manners. The old classification of system A (SNAT1, 2, and 4; Na+-dependent electrogenic transport with 1:1 stoichiometry), also known as SATs, and system N (SNAT3, 5, and 7; electroneutral Na+/H+ antiporters), also recognized as SNs, confuses the prevailing terminology, particularly with the less studied SNAT members. However, these two classes transport different amino acids; system A members with a broader substrate specificity, while system N members with more narrow transport profiles. SNATs are relatively widely distributed throughout the body; however, SNAT1−7 have also been found in the brain and more specifically in the neurons (SNAT1, 2) as well as in astrocytes (SNAT3 and 5). Thus, with SNATs, there is a great potential to achieve intrabrain selective drug delivery, by utilizing system A transporters for neuronal accumulation and system N carriers for astrocytal accumulation. However, the transport mechanism of SNATs and how amino acids are involved in the pH-sensitivity of SNATs have remained unclear to date. Therefore, more detailed insights into the mechanism from higher resolution structures and molecular dynamic simulation (MDS) studies are required to enable rational SNAT-utilizing (pro)drug design.

Selected Publications

Huttunen, J.; Kronenberger, T.; Montaser, A. B.; Králová, A.; Terasaki, T.; Poso, A.; Huttunen, K.M. Sodium-dependent Neutral Amino Acid Transporter 2 (SNAT2) Can Serve As Tertiary Carriers for L-Type Amino Acid Transporter 1 (LAT1)-Utilizing Prodrugs. Molecular Pharmaceutics, 2023, 20(2): 1331-1346.