Proton-Coupled Amino Acid Transporter (Solute Carrier Family 36)

The SLC36 family of proton-coupled amino acid transporters consists of four members, SLC36A1 to SLC36A4. These proteins are involved in the transmembrane movement of amino acids and derivatives.

The ionic coupling and substrate selectivity of the SLC36A1 and SLC36A2 transporters are unusual. Unlike most of mammalian amino acid transporters that function as exchangers or Na+/amino acid symporters, they act as H+/amino acid symporters. SLC36A1, which is expressed at the luminal surface of the human small intestine, is the most thoroughly characterized of the SLC36 family. SLC36A1 can transport a broad range of amino acids and many orally-active amino acid-based drugs and derivatives (including a variety of GABA- and proline-related compounds which can be used for experimental and/or clinical treatment of infections, diabetes, epilepsy, schizophrenia, homocystinuria, cancer cell growth (in vitro) and in photodynamic therapy, fluorescent diagnosis and fluorescent-guided resection of cancer. SLC36A2 is expressed in the apical membrane of the renal proximal tubule. It is involved in the reabsorption of amino acids and derivatives from the renal filtrate. Defects in SLC36A2 result in iminoglycinuria and hyperglycinuria. The function of the two transporters appears to influence the pharmacokinetic profile of amino acid-based drugs by mediating absorption in the small intestine and reabsorption in the kidney.

The H+-coupled amino acid transporter PAT1 (SLC36A1) can transport a number of compounds with potential therapeutic value (shown in blue). Fig.1 The H+-coupled amino acid transporter PAT1 (SLC36A1) can transport a number of compounds with potential therapeutic value (shown in blue). (Thwaites, 2011)

Human SLC36 Family Members

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  1. Thwaites D T and Anderson C M. (2011). The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport. Br J Pharmacol. 164(7): 1802-16.

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