Na(+)/monocarboxylate cotransporter SMCT1 and related proteins; solute-binding domain
SMCT1 is a high-affinity transporter of various monocarboxylates including lactate and pyruvate, short-chain fatty acids, ketone bodies, nicotinate and its structural analogs, pyroglutamate, benzoate and its derivatives, and iodide. Human SMCT1 (hSMCT1, also called AIT) is encoded by the tumor suppressor gene SLC5A8. Its expression is under the control of the C/EBP transcription factor. Its tumor-suppressive role is related to uptake of butyrate, propionate, and pyruvate, these latter are inhibitors of histone deacetylases. SMCT1 is expressed in the colon, small intestine, kidney, thyroid gland, retina, and brain. SMCT1 may contribute to the intestinal/colonic and oral absorption of monocarboxylate drugs. SMCT1 also mediates iodide transport from thyrocyte into the colloid lumen in thyroid gland and through transporting l-lactate and ketone bodies helps maintain the energy status and the function of neurons. In the kidney its expression is limited to the S3 segment of the proximal convoluted tubule (in contrast to the low-affinity monocarboxylate transporter SMCT2, belonging to a different family, which is expressed along the entire length of the tubule). In the retina, SMCT1 and SMCT2 may play a differential role in monocarboxylate transport in a cell type-specific manner, SMCT1 is expressed predominantly in retinal neurons and in retinal pigmented epithelial (RPE) cells. This subgroup belongs to the solute carrier 5 (SLC5) transporter family.
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