Alanine-serine-cysteine amino acid transporter (ASCT) (ASCT)

The Alanine-serine-cysteine amino acid transporter (ASCT) family, primarily consisting of ASCT1 (SLC1A4) and ASCT2 (SLC1A5), functions as sodium-dependent exchangers of small neutral amino acids (UniProt P43007, Q15758). ASCT1 is predominantly expressed in the brain, where it regulates the availability of D-serine and L-serine, which are critical for NMDA receptor activity and proper neurodevelopment (Damseh et al., 2015). ASCT2 is more widely distributed and serves as a major transporter for glutamine, a key nutrient for cell growth and metabolic signaling (Scalise et al., 2018). In many malignancies, ASCT2 is overexpressed to support the high metabolic demands of cancer cells, a phenomenon often referred to as glutamine addiction (Broer, 2014). Consequently, ASCT2 has emerged as a significant therapeutic target in oncology, with inhibitors like V-9302 showing promise in preclinical models by disrupting glutamine metabolism and inducing cell death (Schulte et al., 2018). Beyond cancer, mutations in ASCT1 are linked to severe neurological disorders, highlighting the transporter's essential role in central nervous system homeostasis (Conery et al., 2016). Therapeutic strategies targeting these transporters must balance efficacy against potential neurotoxicity and systemic metabolic disruption.

Other names

SLC1A4SLC1A5Neutral amino acid transporterSATTM7V1RDRC

Competitive inhibition of sodium-dependent neutral amino acid exchange