GLUT: FUNCTIONS, MAIN GLUCOSE TRANSPORTERS - BIOLOGY - 2025

The GLUT are a series of conveyors gate type, in charge of carrying out the passive glucose transport into the cytosol of a wide variety of mammalian cells.

However, most GLUTs that have been identified to date are not specific for glucose. On the contrary, they are capable of transporting different sugars such as mannose, galactose, fructose and glucosamine, as well as other types of molecules such as urates and mannositol.

Typical structure of a GLUT glucose transporter. By A2-33, from Wikimedia Commons.

At least 14 GLUTs have been identified to date. All of them have common structural characteristics and differ both in tissue distribution and in the type of molecule it carries. Therefore, each type seems to be adapted to different physiological conditions where it fulfills a particular metabolic role.

Mobilization of glucose within cells

Most living cells depend on the partial or total oxidation of glucose to obtain the energy necessary to carry out their vital processes.

The entry of this molecule into the cytosol of the cell, where it is metabolized, depends on the help of transporter proteins, since it is large and polar enough to be able to cross the lipid bilayer by itself.

In eukaryotic cells, two major types of transporters involved in the mobilization of this sugar have been identified: the Na + / glucose cotransporters (SGLT) and the GLUT uniporters.

The former use a secondary active transport mechanism, where the Na + cotransport provides the motive energy to carry out the process. While the latter perform a facilitated passive movement, a mechanism that does not require energy and is in favor of the concentration gradient of sugar.

Transport mechanism used by GLUT hexose transporters. By Emma Dittmar - Own work, CC BY-SA 4.0, https: //commons.wikimedia.org/w/index.php? Curid = 64036780

GLUT conveyors

GLUT transporters, for the acronym in English for "Glucose Transporters", are a group of gate-type transporters responsible for carrying out the passive transport of glucose from the extracellular medium to the cytosol.

They belong to the great superfamily of facilitated diffusion transporters (MSF), made up of a large number of transporters responsible for carrying out the transmembrane transport of a wide variety of small organic molecules.

Although their name seems to indicate that they only transport glucose, these transporters have varying specificities for different monosaccharides with six carbon atoms. Therefore, more than glucose transporters, they are hexose transporters.

To date, at least 14 GLUTs have been identified and their location appears to be tissue specific in mammals. That is, each isoform is expressed in very particular tissues.

In each of these tissues, the kinetic characteristics of these transporters vary markedly. The latter seems to indicate that each of them is designed to respond to different metabolic needs.

Structure

The 14 GLUTs that have been identified to date have a series of common structural characteristics.

All of them are integral multipass membrane proteins, that is, they cross the lipid bilayer multiple times through transmembrane segments rich in hydrophobic amino acids.

The peptide sequence of these transporters varies between 490-500 amino acid residues and their three-dimensional chemical structure is similar to that reported for all other members of the major facilitator superfamily (MSF).

This structure is characterized by presenting 12 transmembrane segments in an α-helix configuration and a highly glycosylated extracellular domain that, depending on the type of GLUT, may be located in the third or fifth loop formed.

Additionally, the amino and carboxyl termini of the protein are oriented towards the cytosol and exhibit a certain degree of pseudosymmetry. The way in which these ends are spatially arranged gives rise to an open cavity that constitutes the binding site for glucose or for any other monosaccharide to be transported.

In this sense, the formation of the pore through which the sugar transits downstream of the binding site is defined by a central arrangement of helices 3, 5, 7 and 11. All of these have a high density of polar residues that facilitate the formation of the internal hydrophilic environment of the pore.

Classification

GLUTs have been classified into three large classes based on the degree of similarity of the peptide sequence, as well as the position of the glycosylated domain.

GLUTs belonging to classes I and II limit the highly glycosylated domain to the first extracellular loop located between the first two transmembrane segments. While, in Class III it is restricted to the ninth loop.

In each of these classes, the percentages of homology between the peptide sequences vary between 14 and 63% in less conserved regions and between 30 and 79% in highly conserved regions.

Class I is made up of GLUT1, GLUT2, GLUT3, GLUT 4 and GLUT14 transporters. Class II for GLUT5, 7, 9 and 11. And class III for GLUT6, 8, 10 and 12 and 13.

It is important to mention that each of these transporters has different locations, kinetic characteristics, substrate specificities and functions.

Main glucose transporters and functions

GLUT1

It is expressed mainly in erythrocytes, brain cells, placenta and kidney. Although its main function is to provide these cells with the glucose levels necessary to support cellular respiration, it is responsible for transporting other carbohydrates such as galactose, mannose and glucosamine.

GLUT2

Although highly specific for glucose, GLUT2 has a higher affinity for glucosamine. However, it is also capable of transporting fructose, galactose, and mannose to the cytosol of liver, pancreatic and kidney cells of the small intestine epithelium.

GLUT3

Although it has a high affinity for glucose, GLUT3 also binds and transports galactose, mannose, maltose, xylose, and dehydroascorbic acid with lower affinity.

It is expressed mainly in embryonic cells, so it maintains the continuous transport of these sugars from the placenta to all cells of the fetus. In addition, it has been detected in muscle and testicular cells.

GLUT4

It has a high affinity for glucose and is only expressed in insulin-sensitive tissues. Therefore, it is associated with glucose transport stimulated by this hormone.

GLUT8

It transports both glucose and fructose to the interior of liver, nerve, heart, intestinal, and adipose cells.

GLUT9

In addition to transporting glucose and fructose, it has a high affinity for urates, which is why it mediates their absorption in kidney cells. However, it has been found to be expressed in leukocytes and cells of the small intestine as well.

GLUT12

In skeletal muscle, this transporter is translocated to the plasma membrane in response to insulin, thus acting in response mechanisms to this hormone. Its expression has also been determined in cells of the prostate, placenta, kidney, brain and mammary glands.

GLUT13

It carries out the specific coupled transport of myoinositol and hydrogen. With this, it contributes to lower the pH of the cerebrospinal fluid to values ​​close to 5.0 by nerve cells that make up the cerebellum, hypothalamus, hippocampus and brain stem.

References

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