How does glucose transporter work

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Diabetes Metab 23 : — Endocrinology : — Gastroenterology : — Biochem J : — MFS contains 74 families of membrane transporters including more than 10, members. These transporters transport variety of molecules. Glucose as well as other monosaccharides cannot penetrate the lipid bilayer because they are hydrophilic in nature; therefore, they require specific carrier proteins to undergo diffusion through the bilayer.

Most cells express more than one kind of glucose transporters. However, these membrane carrier proteins are called glucose transporters; they are involved in the transport of several different molecules, not just glucose.

In humans, 14 members of GLUT proteins have been identified. They are encoded by the solute-linked carrier family 2, subfamily A gene family, and SLC2A [ 2 , 3 ]. These domains are connected by hydrophilic loop between TM6 and TM7 of the protein [ 4 , 5 , 6 ]. As was proposed for GLUT1, helices 1, 2, 4, 5, 7, 8, 10, and 11 form an inner bundle that is stabilized by the outer helices 3, 6, 9, and 12 [ 8 ]. The human GLUTs are involved in the transport of the several hexoses in addition to myoinositol, urate, glucosamine, and ascorbate [ 7 ].

He proposed that these symporters have two binding sites: one for glucose and one for sodium [ 13 ]. In humans, 12 members of sodium-dependent glucose cotransporters have been identified. These proteins contain of — amino acid residues, with a predicted mass of 60—80 kDa.

There is a diversity in gene structure. Both the hydrophilic N- and C-termini are located on the extracellular side of the cell membrane [ 1 ]. SGLTs are highly glycosylated membrane proteins; however, glycosylation is not required in the functioning of the protein.

They act by alternating between two states. First, the transporter has an opening facing the outside of the cell, and it picks up a molecule of glucose.

Then it shifts shape, and opens towards the inside, releasing glucose into the cell. Glucose transporters generally act passively: since glucose is rapidly phosphorylated by hexokinase , the concentration of free glucose in the cytoplasm is generally very low, and the higher concentration of glucose in the blood drives transport of glucose into the cell. The human genome encodes 14 similar transporters that deliver glucose and other sugars into different types of cells.

GLUT2 helps control the flow of glucose in and out of liver cells, and pancreatic beta cells use it to monitor the level of glucose in the blood, releasing insulin when the level rises. Nerve cells in the brain require a constant supply of glucose, so they use GLUT3 PDB entry 4zwc , a form that works well even when glucose levels are low.

GLUT4 is activated by insulin and is used by fat and muscle cells to gather glucose after meals. When we eat a meal, insulin is released into the blood, telling cells that glucose is available. In response, fat and muscle cells move many GLUT4 transporters to their cell membranes, to gather a supply of glucose while it is plentiful.

However, in people with type II diabetes, the body becomes resistant to the action of insulin—both in the production of insulin and in the sites where it acts.

One consequence is that less GLUT4 is moved to the membranes of muscle cells after meals, so less glucose is taken up from the blood. LacY transports lactose and hydrogen ions into the cell, and GlpT transports phosphate and glycerolphosphate in opposite directions.

The GLUT family is part of a larger group of transporters, collectively termed the major facilitator superfamily. They share a similar mechanism, with two domains that rock back and forth to transport molecules across membranes.