Na(+)/monocarboxylate cotransporters SMCT1 and 2 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. 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. It 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. SMCT2 is a low-affinity transporter for short-chain fatty acids, lactate, pyruvate, and nicotinate. hSMCT2 is encoded by the SLC5A12 gene. SMCT2 is expressed in the kidney, small intestine, skeletal muscle, and retina. In the kidney, SMCT2 may initiate lactate absorption in the early parts of the tubule, SMCT1 in the latter parts of the tubule. In the retina, SMCT1 and SMCT2 may play a differential role in monocarboxylate transport in a cell type-specific manner. This subgroup belongs to the solute carrier 5 (SLC5) transporter family.