Neutral amino acid transporters (SLC transporters)

Amino acid transporters for glutamine and other neutral/essential amino acids are a diverse group of membrane-bound proteins, primarily from the Solute Carrier (SLC) families, that facilitate the movement of nutrients across cellular membranes [UniProt Q15758, P48023]. Key members include SLC1A5 (ASCT2), which mediates glutamine uptake, and SLC7A5 (LAT1), which transports large neutral amino acids like leucine and phenylalanine [PubMed 29459736]. These transporters are essential for maintaining cellular homeostasis, supporting protein synthesis, and activating the mTORC1 signaling pathway, which regulates cell growth and metabolism [PubMed 32196945]. In many cancers, these transporters are significantly overexpressed to satisfy the high metabolic demands of rapidly dividing cells, making them attractive targets for oncology therapeutics [Cell 2011]. Drugs such as V-9302 and JPH203 have been developed to inhibit these transporters, effectively "starving" tumor cells of critical nutrients [Nature Medicine 2018]. Additionally, these transporters are utilized for the delivery of amino acid-based radiopharmaceuticals and prodrugs like Melphalan [PubMed 32196945]. However, therapeutic targeting is complicated by the widespread expression of these transporters in healthy tissues, such as the blood-brain barrier and the intestinal epithelium, which can lead to off-target toxicities [UniProt P48023].

Other names

Solute carrier family amino acid transportersGlutamine transportersSystem L transportersSystem ASC transportersLarge neutral amino acid transportersSLC1A5SLC7A5SLC38 familyASCT2LAT1

Inhibition of amino acid uptake via competitive or non-competitive binding to the transporter pore, leading to nutrient deprivation and inhibition of downstream growth signaling pathways such as mTORC1 [PubMed 29459736, 32196945].