2.A.18.6.15
Neutral amino acid transporter 5 (Solute carrier family 38 member 5, SNAT5) (System N transporter 2, SN2).  Transports glutamine, histidine and glycine as well as other amino acids.  Present in glial cells where it probably functions in neurotransmitter clearance from synapses (Rodríguez et al. 2014). May also take up cisplatin (Girardi et al. 2020). SLC38A5 is a metabolic regulator of retinal angiogenesis by controlling amino acid nutrient uptake and homeostasis in endothelial cells (Wang et al. 2022).  SLC38A5/SNAT5 is a system N transporter that can mediate net inward or outward transmembrane fluxes of neutral amino acids coupled with Na⁺ (symport) and H⁺ (antiport). Its preferential substrates are amino acids with side chains containing amide (glutamine, and asparagine) or imidazole (histidine) groups, but also serine, glycine and alanine are transported by the carrier. Expressed in the pancreas, intestinal tract, brain, liver, bone marrow, and placenta, it is regulated at mRNA and protein levels by mTORC1 and WNT/beta-catenin pathways, and it is sensitive to pH, nutritional stress, inflammation, and hypoxia. SNAT5 expression has been found to be altered in pathological conditions such as chronic inflammatory diseases, gestational complications, chronic metabolic acidosis and malnutrition. Growing experimental evidence shows that SNAT5 is overexpressed in several types of cancer cells. Moreover, recently published results indicate that SNAT5 expression in stromal cells can support the metabolic exchanges occurring in the tumor microenvironment of asparagine-auxotroph tumors. Taurino et al. 2023 reviewed the functional roles of the SNAT5 transporter in pathophysiology, and they propose that, due to its peculiar operational and regulatory features, SNAT5 plays pro-cancer roles when expressed either in neoplastic or in stromal cells ofglutamine-auxotroph tumors.