ASC transporters mediate Na⁺-dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr and their structure is predicted to be similar to that of the glutamate transporters [2,12]. ASCT1 and ASCT2 also exhibit thermodynamically uncoupled chloride channel activity associated with substrate transport [1,4,13]. Whereas EAATs counter-transport K⁺ (see above) ASCTs do not and their function is independent of the intracellular concentration of K⁺ [1,13].

The substrate specificity of ASCT1 may extend to L-proline and trans-4-hydroxy-proline [10]. At low pH (~5.5) both ASCT1 and ASCT2 are able to exchange acidic amino acids such as L-cysteate and glutamate [11-12]. In addition to the inhibitors tabulated above, HgCl₂, methylmercury and mersalyl, at low micromolar concentrations, non-competitively inhibit ASCT2 by covalent modificiation of cysteine residues [9].

1. Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters. Br J Pharmacol, 176 Suppl 1: S397-S493. [PMID:31710713]

2. Arriza JL, Kavanaugh MP, Fairman WA, Wu YN, Murdoch GH, North RA, Amara SG. (1993) Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family. J Biol Chem, 268 (21): 15329-32. [PMID:8101838]

3. Bröer A, Brookes N, Ganapathy V, Dimmer KS, Wagner CA, Lang F, Bröer S. (1999) The astroglial ASCT2 amino acid transporter as a mediator of glutamine efflux. J Neurochem, 73 (5): 2184-94. [PMID:10537079]

4. Bröer A, Wagner C, Lang F, Bröer S. (2000) Neutral amino acid transporter ASCT2 displays substrate-induced Na+ exchange and a substrate-gated anion conductance. Biochem J, 346 Pt 3: 705-10. [PMID:10698697]

5. Esslinger CS, Cybulski KA, Rhoderick JF. (2005) Ngamma-aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site. Bioorg Med Chem, 13 (4): 1111-8. [PMID:15670919]

6. Grewer C, Grabsch E. (2004) New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+-dependent anion leak. J Physiol (Lond.), 557 (Pt 3): 747-59. [PMID:15107471]

7. Hassanein M, Qian J, Hoeksema MD, Wang J, Jacobovitz M, Ji X, Harris FT, Harris BK, Boyd KL, Chen H et al.. (2015) Targeting SLC1a5-mediated glutamine dependence in non-small cell lung cancer. Int J Cancer, 137 (7): 1587-97. [PMID:25821004]

8. Lopes C, Pereira C, Medeiros R. (2021) ASCT2 and LAT1 Contribution to the Hallmarks of Cancer: From a Molecular Perspective to Clinical Translation. Cancers (Basel), 13 (2). [PMID:33429909]

9. Oppedisano F, Galluccio M, Indiveri C. (2010) Inactivation by Hg2+ and methylmercury of the glutamine/amino acid transporter (ASCT2) reconstituted in liposomes: Prediction of the involvement of a CXXC motif by homology modelling. Biochem Pharmacol, 80 (8): 1266-73. [PMID:20599776]

10. Pinilla-Tenas J, Barber A, Lostao MP. (2003) Transport of proline and hydroxyproline by the neutral amino-acid exchanger ASCT1. J Membr Biol, 195 (1): 27-32. [PMID:14502423]

11. Tamarappoo BK, McDonald KK, Kilberg MS. (1996) Expressed human hippocampal ASCT1 amino acid transporter exhibits a pH-dependent change in substrate specificity. Biochim Biophys Acta, 1279 (2): 131-6. [PMID:8603078]

12. Utsunomiya-Tate N, Endou H, Kanai Y. (1996) Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter. J Biol Chem, 271 (25): 14883-90. [PMID:8662767]

13. Zerangue N, Kavanaugh MP. (1996) ASCT-1 is a neutral amino acid exchanger with chloride channel activity. J Biol Chem, 271 (45): 27991-4. [PMID:8910405]

14. Zerangue N, Kavanaugh MP. (1996) Flux coupling in a neuronal glutamate transporter. Nature, 383 (6601): 634-7. [PMID:8857541]