System N amino acid transporter (SNAT) (SNAT)

System N amino acid transporters, primarily comprising SNAT3 (SLC38A3) and SNAT5 (SLC38A5), are sodium-dependent, electrogenic symporters that facilitate the exchange of neutral amino acids—most notably glutamine, asparagine, and histidine—for protons (UniProt: Q99624). These transporters are essential for maintaining nitrogen homeostasis and are predominantly expressed in the liver and the central nervous system. In the brain, they are localized to astrocytes and play a critical role in the glutamate-glutamine cycle by mediating the efflux of glutamine, which is then taken up by neurons to synthesize the neurotransmitters glutamate and GABA (PMID: 25849132). In the liver, System N transporters facilitate the uptake and release of glutamine to support the urea cycle and gluconeogenesis (PMID: 11306701). Recent research has highlighted the upregulation of these transporters, particularly SLC38A5, in various cancers where they support the high metabolic demand for glutamine required for rapid cell proliferation and mTOR signaling (PMID: 29335505). Consequently, System N transporters are emerging as potential therapeutic targets for metabolic reprogramming in oncology, although their inhibition must be carefully managed to avoid disrupting essential neurological and hepatic functions (PMID: 15084518). Experimental inhibitors like L-gamma-glutamyl-p-nitroanilide (GPNA) are currently used in research to study the effects of blocking these transporters on cell proliferation and signaling (PMID: 24651010).

Other names

SLC38A3SLC38A5SNAT3SNAT5SN1SN2Sodium-coupled neutral amino acid transporter

Inhibition of sodium-dependent, proton-coupled transport of neutral amino acids (primarily glutamine) to disrupt tumor metabolism or modulate the glutamate-glutamine cycle in the central nervous system.