Glucosetransporter

Glucose transporter (GLUT, SLC2A ) are specific transmembrane transport proteins that catalyze the transport of glucose or fructose through the cell membrane. Is the carrier protein -mediated Uniports, wherein the concentration gradient of glucose provides the energy required for transport.

All GLUTs are members of the sugar transporter in the major facilitator superfamily of membrane transport proteins. They have twelve transmembrane domains.

• 2.2.1 GLUT5
• 2.2.2 GLUT7
• 2.2.3 GLUT9
• 2.2.4 GLUT11

• 2.3.1 GLUT6
• 2.3.2 GLUT8
• 2.3.3 GLUT10
• 2.3.4 GLUT12

Structure

So far, 14 different transporters of the GLUT- type known to be divided into three classes. Each GLUT consists of twelve amphiphilic transmembrane domains, the so -assemble in the plasma membrane that bind the hydrophobic portions outward into the membrane and in the middle of a hydrophilic pore for Glucose is produced. Here are the amino-terminus and carboxyl -terminus on the cytosolic side ( intracellular). The binding of glucose causes a conformational change of the molecule will be transported to the other side ( "rocker switch ", tilting ). On the restoration of the original conformation are unknown.

Types and development

Due to similarities in the amino acid sequence of the GLUT to be divided into three classes. GLUT1 and GLUT3 are also permeable to dehydroascorbate. GLUT5 transports mainly fructose and uric acid GLUT9.

Based on the amino acid sequences now known GLUTs can be concluded that GLUT type 3 are the oldest GLUTs; they are probably originated with eukaryotes and can be found orthologs of them also in plants. With the evolution of chordates the GLUT created by additional gene copy type 2 Another gene duplication in the course of Euteleostomi finally brought GLUT type 1 wherein GLUT -14 emerged as a recent development with the primates from a copy of GLUT -3.

Type 1

GLUT1

GLUT1 is the most common type and occurs in many mammalian cells. Especially in the cells of the CNS and the erythrocytes of this type is frequently encountered, so it is assumed that it constitutes a special role in the nutrients of this glucose -dependent cells. He is an insulin-dependent transporter, its Km value is 1.5 mmol · l -1. Therefore, it shows a high affinity for glucose and is almost saturated under physiological conditions. As a continuous uptake of glucose into the cells is ensured.

GLUT2

It is found in hepatocytes, in the β - cells of the pancreas, in the intestinal mucosa and in the epithelial cells of the kidney. The van is also independent of insulin, but has only a low glucose affinity ( KM between 17-66 mmol · l -1). Consequently, the glucose uptake is dependent on the blood glucose levels. Thus, the insulin synthesis and release is activated in the β - cells and inhibited the glycogen of the liver.

GLUT3

GLUT3 occurs mainly, but not only in nerve cells of the brain. Due to the lower KM compared to GLUT2 sufficient glucose uptake is ensured even at low blood glucose levels. He is insulin- independent and serves as a supply of the CNS.

GLUT4

GLUT4 is present in the fat cells, and in all striated muscle ( skeletal muscle cells and heart muscle cells). The transporter is insulin-dependent, has a high affinity, and is stored in the membrane of intracellular vesicles. With increasing concentration of blood sugar levels, also increases the insulin levels. Insulin mediates the fusion of the vesicles with the plasma membrane, so that the blood sugar levels by uptake of glucose can be lowered into the cells. After that, the transporters are resumed by endocytosis and can be used again. In fat cells, the glucose can be converted into the triacylglycerol, is stored in form of glycogen in muscle. GLUT4 therefore has the function of a needs-based glucose supply.

GLUT14

Occurs exclusively in the testis and has structurally very similar to GLUT3.

Type 2

GLUT5

This guy is not a pure glucose, but a Fructosetransporter and occurs mainly in the spermatozoa in the intestinal tract and in the kidney.

GLUT7

This transporter is used to transport the gluconeogenesis in the liver resulting in the glucose from the cells into the blood. It must first be glucose -6-phosphate dephosphorylation of glucose - 6-phosphatase localized at the endoplasmatic reticulum.

GLUT9

GLUT -9 is mainly to be found in the renal tubules, where he reabsorbed uric acid. To a lesser extent two isoforms are expressed in several different tissue types and may additionally carry small amounts of fructose and glucose.

GLUT11

About this glucose transporter is only known that it is expressed in three isoforms in cardiac and skeletal muscle cells.

Type 3

GLUT6

GLUT -6 in the brain, spleen and is expressed in peripheral leukocytes.

GLUT8

GLUT 8 transported in testicular cells competitively glucose and fructose. Its expression is inhibited by estrogen.

GLUT10

Expressed in many tissue types, but especially in the liver and pancreas, is one of the GLUT Km = 0.28 mM for 2-deoxy- D-glucose.

GLUT12

GLUT -12 is a membrane protein in the perinuclear region of muscle cells, while insulin is absent.

Function

Monosaccharides such as glucose, are to be transported in both water and in the blood soluble ( polar) and can therefore easily through the blood to the target cells. The ( non-polar ) lipid bilayer of cells for glucose but hard permeable, so there is glucose transporters in the plasma membranes that allow facilitated diffusion. They work purely without energy consumption due to the chemical gradient for glucose.

For this necessary concentration gradient between intracellular and extracellular space is maintained, the glucose reacts after entry into the cytosol to glucose -6 -phosphate ( G6P ), which by the hexokinase ( different isoforms ) is catalyzed. G6P is the starting product of glycolysis, the pentose phosphate pathway and glycogen synthesis.

GLUT1, GLUT3 and GLUT4 and hexokinase IV are the glucose primary care of the body that are still working even with low blood sugar levels effectively, as they have a low Km ( and therefore a high affinity). It is important that the amount of glucose, which is metabolized in the cell only depends on the amount of hexokinase inside the cell and not from the blood sugar level.

GLUT2 and glucokinase, however, are dependent on the concentration of blood sugar in their activity, as they have a low affinity (high Km). This means that the uptake of glucose is carried out only if there is a hyperglycemia. They thus serve as a kind of glucose sensor. Is there a glucose deficiency, so that is out the supply to the organs and muscles (of particular importance is the supply of red blood cells and the central nervous system with glucose, as these are dependent on a minimum glucose concentration) ensured before glucose is stored in the liver cells or fat cells.

The glucokinase in the pancreatic ensures that produced in response to blood glucose concentration and sufficient insulin secreted. If in these cells, the hexokinase localized, the β - cells were completely conformist and would constantly pour out insulin.

Most of the cells are not able to synthesize free glucose itself, since they lack the glucose-6- phosphatase. They are thus dependent on a supply of the blood. Only hepatocytes and causes intestinal and kidney cells are able to operate gluconeogenesis.

Medical importance

Defects in GLUT can cause several rare inherited disorders.

• The GLUT1 deficiency syndrome, an autosomal dominant inherited disease caused by a defect in GLUT1.
• Induced by genetic defects GLUT -2 deficiency leads to the so-called Fanconi -Bickel syndrome.
• Certain symptoms in a subset of patients suffering from diabetes mellitus type 2, could be associated with mutations in GLUT -2.
• Mutations in the gene encoding for GLUT -9 is responsible for a hereditary form of hypouricemia.
• Defects in GLUT -10 cause a disease that is associated with hyperextensibility arteries and connective tissue ( arterial tortuosity syndrome, ATS).