The proteins sodium-glucose transport (SGLT) are responsible for carrying the active glucose transport in mammalian cells against a concentration gradient. The energy required to make this transport possible is acquired from the sodium cotransport in the same direction (symport).
Its location is limited to the membrane of the cells that form the epithelial tissues responsible for the absorption and reabsorption of nutrients (small intestine and the proximal convoluted tubule of the kidney).
Glucose transporters SGLT, unlike GLUTs, carry out the transport of glucose and sodium against their concentration gradient. By NuFS, San Jose State University, modified of Wikimedia Commons.
To date, only six isoforms belonging to this family of transporters have been described: SGLT-1, SGLT-2, SGLT-3, SGLT-4, SGLT-5 and SGLT-6. In all of them, the electrochemical current generated by the transport of the sodium ion provides energy and induces the conformational change in the structure of the protein necessary to translocate the metabolite to the other side of the membrane.
However, all these isoforms differ from each other by presenting differences in:
- The degree of affinity they have for glucose,
- The ability to carry out the transport of glucose, galactose and amino acids,
- The degree to which they are inhibited by florizin and
- The tissue location.
Molecular mechanisms of Glucose transport
Glucose is a six-carbon monosaccharide that is used by most existing cell types for energy through metabolic oxidation pathways.
Given its large size and essentially hydrophilic nature, it is unable to cross cell membranes by free diffusion. Therefore, their mobilization to the cytosol depends on the presence of transport proteins in said membranes.
The glucose transporters studied so far carry out the transport of this metabolite by passive or active transport mechanisms. Passive transport differs from active transport in that it does not require an energy supply to be carried out, since it occurs in favor of a concentration gradient.
The proteins involved in the passive transport of glucose belong to the family of GLUTs facilitated diffusion transporters, named after the acronym in English of the term "Glucose Transporters". While those that carry out an active transport of it have been called SGLT for "sodium-glucose transport proteins".
The latter obtain the free energy necessary to carry out the transport of glucose against its concentration gradient of the cotransport of the sodium ion. At least 6 isoforms of SGLT have been identified and their location appears to be restricted to epithelial cell membranes .
SGLT Features
The SGLT transporters are not specific for glucose, they are capable of transporting another variety of metabolites such as amino acids, galactose, and other metabolites, and for this they use the energy released by the sodium ion cotransport in favor of its concentration gradient. By speciLadyofHats).push ({});
The most widely studied function of this type of transporter is the reabsorption of glucose in the urine.
This reabsorption process involves the mobilization of carbohydrate from the renal tubules through the cells of the tubular epithelium to the lumen of the peritubular capillaries. Being the isoform of high capacity and affinity for glucose SGLT-2, which is the main contributor.
The glucose absorption function in the intestinal tract is attributed to SGLT-1, a transporter that despite having a low capacity has a high affinity for glucose.
The third member of this family, SGLT3, is expressed in the membranes of skeletal muscle cells and the nervous system, where it appears not to act as a glucose transporter but rather as a sensor of the concentrations of this sugar in the extracellular medium.
The functions of the SGLT4, SGLT5 and SGLT6 isoforms have not been determined so far.
References
- Abramson J, Wright EM. Structure and function of Na symporters with inverted repeats. Curr Opin Struct Biol. 2009; 19: 425-432.
- Alvarado F, Crane RK. Studies on the mechanism of intestinal absorption of sugars. VII. Phenylglycoside transport and its possible relationship to phlorizin inhibition of the active transport of sugars by the small intestine. Biochim Biophys Acta. 1964; 93: 116-135.
- Charron FM, Blanchard MG, Lapointe JY. Intracellular hypertonicity is responsible for water flux associated with Na_ / glucose cotransport. Biophys J. 2006; 90: 3546-3554.
- Chen XZ, Coady MJ, Lapointe JY. Fast voltage clamp discloses a new component of presteady-state currents from the Na_-glucose cotransporter. Biophys J. 1996; 71: 2544-2552.
- Dyer J, Wood IS, Palejwala A, Ellis A, Shirazi-Beechey SP. Expression of monosaccharide transporters in intestine of diabetic humans. Am J Physiol Gastrointest Liver Physiol. 2002; 282: G241-G248.
- Soták M, Marks J, Unwin RJ. Putative tissue location and function of the SLC5 family member SGLT3. Exp Physiol. 2017; 102 (1): 5-13.
- Turk E, Wright EM. Membrane topology motifs in the SGLT cotransporter family. J Membr Biol. 1997; 159: 1-20.
- Turk E, Kim O, le Coutre J, Whitelegge JP, Eskandari S, Lam JT, Kreman M, Zampighi G, Faull KF, Wright EM. Molecular characterization of Vibrio parahaemolyticus vSGLT: a model for sodium-coupled sugar cotransporters. J Biol Chem. 2000; 275: 25711-25716.
- Taroni C, Jones S, Thornton JM. Analysis and prediction of carbohydrate binding sites. Protein Eng. 2000; 13: 89-98.
- Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011; 91 (2): 733-794.