Glucose transporters

 Glucose transporters

Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. 14 GLUTS are encoded by human genome. GLUT is a type of uniporter transporter protein.

Types- Each glucose transporter iso form plays a specific role in glucose metabolism determined by its pattern of tissue expression, substrate specificity, transport kinetics, and regulated expression in different physiological conditions. To date, 14 members of the GLUT/SLC2 have been identified. On the basis of sequence similarities, the GLUT family has been divided into three subclasses

Class I- Class I comprises the well-characterized glucose transporters GLUT1-GLUT4.

GLUT1-Is widely distributed in fetal tissues. In the adult, it is expressed at highest levels in erythrocytes and also in the endothelial cells of barrier tissues such as the blood–brain barrier. It is responsible for the low level of basal glucose uptake required to sustain respiration in all cells.

GLUT2- Is a bidirectional transporter, allowing glucose to flow in 2 directions. It is expressed by renal tubular cells, liver cells and pancreatic beta cells. It is also present in the basolateral membrane of the small intestine epithelium. Bidirectionality is required in liver cells to uptake glucose for Glycolysis and Glycogenesis, and release of glucose during Gluconeogenesis.

In pancreatic beta cells, free flowing glucose is required so that the intracellular environment of these cells can accurately gauge the serum glucose levels. All three monosaccharide (glucose, galactose, and fructose) are transported from the intestinal mucosal cell into the portal circulation by GLUT2.

GLUT3- Expressed mostly in neurons (where it is believed to be the main glucose transporter iso form), and in the placenta.

GLUT4-Expressed in adipose tissues and striated muscle (skeletal muscle  and  cardiac muscle).

GLUT14-Expressed in testes

Class II- comprises the following; functions of some of them are not clear -

·         GLUT5 (SLC2A5), a fructose transporter in enterocytes

·         GLUT7 (SLC2A7), found in the small and large intestine, transporting glucose out of the endoplasmic reticulum

·         GLUT9 - (SLC2A9)

·         GLUT11- (SLC2A11)

Class III- comprises the following; functions of some of them are not clear-

·         GLUT6 (SLC2A6)

·         GLUT8 (SLC2A8)

·         GLUT10 (SLC2A10)

·         GLUT12 (SLC2A12)

·         GLUT13, (SLC2A13) primarily expressed in brain.

Secondary Active Transport or Co transport

In secondary active transport, also known as coupled transport or co transport, energy is used to transport molecules across a membrane; however, in contrast to primary active transport, there is no direct coupling of ATP.

Instead, it relies upon the electrochemical potential difference created by pumping ions in or out of the cell. Permitting one ion or molecule to move down an electrochemical gradient, but possibly against the concentration gradient where it is more concentrated to that where it is less concentrated, increases entropy and can serve as a source of energy for metabolism (e.g. in ATP synthase). The energy derived from the pumping of protons across a cell membrane is frequently used as the energy source in secondary active transport.

In humans, sodium (Na⁺) is a commonly co transported ion across the plasma membrane, whose electrochemical gradient is then used to power the active transport of a second ion or molecule specially glucose against its gradient.  It is known as Sodium Glucose co transport. Hydrogen pumps are also used to create an electrochemical gradient to carry out processes within cells such as in the electron transport chain of the cell.

Co transporters can be classified as

·        Symporters- A symporter is an integral membrane protein that is involved in the transport of two different molecules across the cell membrane in the same direction. The symporter works in the plasma membrane and molecules are transported across the cell membrane at the same time. It is, therefore, a type of co transporter. The transporter is called a symporter because the molecules will travel in the same direction in relation to each other. The ions will move down the electrochemical gradient, allowing the other molecules to move against the concentration gradient. The movement of the ions across the membrane is facilitated diffusion, and is coupled with the active transport of the molecule(s).

·        Antiporters -An antiporter, also called exchanger or counter-transporter, is a co transporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a Phospholipid membrane such as the plasma membrane in opposite directions, one into the cell and one out of the cell.  Na⁺/H⁺ antiporters have been observed.

·        Uniporter- A uniporter is a membrane transport protein that transports a single species of substrate, charged or uncharged, across a cell membrane. It may use either facilitated diffusion and transport along a diffusion gradient or transport against one with an active transport process. Uniporters include both carriers and ion channels, and are referred to as facilitated transporters, suggesting movement down a concentration or electrochemical gradient.