Sodium-coupled monocarboxylate transporter 1

Sodium-coupled monocarboxylate transporter 1 (i.e., SMCT1) and sodium-coupled monocarboxylate transporter 2 (i.e., SMCT2) are plasma membrane transport proteins in the solute carrier family. They transport sodium cations in association with the anionic forms (see conjugated base) of certain short-chain fatty acids (i.e., SC-FAs) through the plasma membrane from the outside to the inside of cells. For example, propionic acid (i.e., CH
₃CH
₂CO
₂H) in its anionic "propionate" form (i.e., CH
₃CH
₂CO⁻
₂) along with sodium cations (i.e., Na⁺) are co-transported from the extracellular fluid into a SMCT1-epxressing cell's cytoplasm. Monocarboxylate transporters (MCTs) are also transport proteins in the solute carrier family. They co-transport the anionic forms of various compounds into cells in association with proton cations (i.e. H⁺). Four of the 14 MCTs, i.e. SLC16A1 (i.e., MCT1), SLC16A7 (i.e., MCT22), SLC16A8 (i.e., MCT3), and SLC16A3 (i.e., MCT4), transport some of the same SC-FAs anions that the SMCTs transport into cells. SC-FAs do diffuse into cells independently of transport proteins but at the levels normally occurring in tissues far greater amounts of the SC-FAs are brought into cells that express a SC-FA transporter.

The human SMCT1 and SMCT2 proteins are commonly referred to by the names of the genes responsible for their production, i.e., SLC5A8 and SLC5A12, respectively. The human gene for SMCT1, i.e., the SLC5A8 gene, is located at position 23.1 on the "q" (i.e., long) arm of chromosome 12 (notated as 12q23); SMCT2's gene, i.e., the SLC5A12 gene, is located at position 14.2 on the "p" (i.e., short) arm of chromosome 11 (notated as chromosome 11p14.2) The SMCT1 and SMCT2 proteins consist of 618(https://www.uniprot.org/uniprotkb/Q8N695/entry) and 618 amino acids, respectively, and have 57% identity at the amino acid level. (The animal proteins are, like the human proteins, here termed SMCT1 and SMCT2 while their genes are termed Slc8a5 and Slc5a12, respectively.) Compared to SMCT1, there have been far fewer reported studies on SMCT2.

SC-FAs come from two sources: the diet and, perhaps more importantly, their release from intestinal bacteria. The intestinal SC-FAs diffuse into the intestine/s wall, enter SMCT1-bearing cells, and diffuse into the blood. These SA-FAs serve as energy sources for cells located in the intestinal wall and throughout the body. The absorbed SC-FAs also stimulate various functions in cells throughout the body that express one of the SC-FA receptors, i.e., free fatty acid receptor 2, free fatty acid receptor 3, or hydroxycarboxylic acid receptor 2. (For the functions elicited by SC-FA's activation of these receptors see free fatty acid receptor 2 functions, free fatty acid receptor 3 functions, and hydroxycarboxylic acid receptor 2 functions.) SMCT1 thereby functions to take up intestinal SC-FAs that have nutritional and wide-ranging stimulating effects. SMCT1 has other functions. SMCT1-expressing cells in the kidney and salivary glands retrieve the SC-FAs in the urine and saliva, respectively, which otherwise would be wastefully discarded. Furthermore, the SC-FAs that enter cells can activate signal transduction pathways which elicit cellular responses independently of the three cited SC-FA receptors. This appears to the mechanism underlying the ability of high SMCT1 levels in kidney cells to ameliorate diabetic kidney disease. It may also underlie the apparent ability of high SMCT1 levels to suppress the development and/or progression of breast, pancreas, lung, brain, thyroid, stomach, prostate, and head & neck cancers. However, these anti-cancerous effects are based primarily on studies finding that, compared to the normal cells in the tissues of these cancers, the cancer cells expressed lower levels of the messenger RNA (i.e., mRNA) that directs formation of the SMCT1 protein. Most of these studies did not measure the levels of SMCT1 protein but rather inferred their levels based on their SMCT1 mRNA levels. Studies have shown that the relation between the level of a mRNA and its protein can vary greatly, i.e., that SMCT1 mRNA levels are not always good indicators of SMCT1 protein levels. This and discrepant findings in studies on colon and pancreas cancers indicate that the role of SMCT1 protein in these cancers requires further investigations.