Members of the solute carrier (SLC) 36 family are involved in transmembrane movement of
amino acids and derivatives. SLC36 consists of four members. SLC36A1 and SLC36A2 both function as H(+) -coupled
amino acid symporters. SLC36A1 is expressed at the
luminal surface of the small intestine but is also commonly found in lysosomes in many cell types (including neurones), suggesting that it is a multipurpose carrier with distinct roles in different cells including absorption in the small intestine and as an efflux pathway following intralysosomal
protein breakdown. SLC36A1 has a relatively low affinity (K(m) 1-10 mM) for its substrates, which include zwitterionic amino and
imino acids, heterocyclic
amino acids and
amino acid-based drugs and derivatives used experimentally and/or clinically to treat
epilepsy,
schizophrenia,
bacterial infections, hyperglycaemia and
cancer. SLC36A2 is expressed at the apical surface of the human renal proximal tubule where it functions in the reabsorption of
glycine,
proline and
hydroxyproline. SLC36A2 also transports
amino acid derivatives but has a narrower substrate selectivity and higher affinity (K(m) 0.1-0.7 mM) than SLC36A1. Mutations in SLC36A2 lead to hyperglycinuria and
iminoglycinuria. SLC36A3 is expressed only in testes and is an orphan transporter with no known function. SLC36A4 is widely distributed at the
mRNA level and is a high-affinity (K(m) 2-3 µM) transporter for
proline and
tryptophan. We have much to learn about this family of transporters, but from current knowledge, it seems likely that their function will influence the pharmacokinetic profiles of
amino acid-based drugs by mediating transport in both the small intestine and kidney.