The movement of glucose into an erythrocyte is an example of facilitated diffusion mediated by a uniport carrier protein. The concentration of glucose in blood plasma is usually in the range of 65-90 mg/100 mL or about 3.6-5.0 mM. The erythrocyte (or almost any other cell in contact with the blood, for that matter) is capable of glucose uptake by facilitated diffusion because of its low intracellular glucose concentration and the presence in its plasma membrane of a glucose carrier protein or glucose transporter, abbreviated as GLUT. The GLUT of erythrocytes is called GLUT1 to distinguish it from related GLUTs in other mammalian tissues. GLUT1 allows glucose to enter the cell about 50,000 times faster than it would by free diffusion through a lipid bi-layer.
GLUT1-mediated uptake of glucose displays all of the classic features of facilitated diffusion — it is specific for glucose (and a few related sugars, such as galactose and man-nose) — exhibits saturation kinetics and is susceptible to competitive inhibition by related monosaccharides. GLUT1 is an integral membrane protein with 12 hydrophobic trans-membrane segments. These are presumably folded and assembled in the membrane to form a cavity lined with hydrophilic side-chains that form hydrogen bonds with glucose molecules as they move through it.
GLUT1 is thought to transport glucose by an alternating conformation mechanism. The two conformational states are called T1, which has the binding site for glucose open to the outside of the cell, and T2, with the site open to the interior of the cell. The process begins when a molecule of D-glucose collides with and binds to a GLUT1 molecule that is in its T1 conformation. With glucose bound, GLUT1 now shifts to its T2, conformation. The conformational change allows the release of the glucose molecule to the interior of the cell, after which the GLUT1 molecule returns to its original conformation, with the binding site again facing outwards.
The process is readily reversible because carrier proteins function equally well in either direction. A carrier protein is really a gate in an otherwise impenetrable wall, and, like most gates, it facilitates traffic in either direction. Individual solute molecules may be transported either inward or outward, with the net direction of solute movement determined by the relative concentrations of the solute on the two sides of the membrane. If the concentration is higher outside, net flow will be inward; consequently, if the higher concentration occurs inside, net flow will be outward.
GLUT1 is just one of several glucose transporters in mammals. Each of these proteins is encoded by a separate gene and each has physical and kinetic characteristics that suit it especially for the specific tissues in which it is found. For example, GLUT2, the glucose transporter present in liver cells, has kinetic properties that adapt it well to its role in transporting glucose out of the cells when liver glycogen is broken down to replenish the supply of glucose in the blood.
The low intracellular glucose concentration that makes facilitated diffusion possible for most animal cells exists because incoming glucose is quickly phosphorylated to glucose-6-phosphate by the enzyme hexokinase, with ATP as the phosphate donor and energy source. This hexokinase reaction is the first step in glucose metabolism.
The low Km of hexokinase for glucose (1.5 mM) and the highly exergonic nature of the reaction (AG0’ = – 4.0 kcal/mol) ensures that the concentration of glucose within the cell is kept low. For many mammalian cells, the intracellular glucose concentration ranges from 0.5 to 1.0 mM, about 15-20 per cent of the glucose level in the blood plasma outside the cell.
The phosphorylation of glucose also has the effect of locking glucose in the cell, because the plasma membrane of the erythrocyte does not have a transport protein for glucose-6-phosphate. (GLUT1, like most sugar transporters, does not recognise the phosphorylated form of the sugar.) This is, in fact, a general strategy for retaining molecules within the cell because most do not have membrane proteins capable of transporting phosphorylated compounds.
The writer is associate professor, head, department of botany, Ananda Mohan College, Kolkata, and also fellow, botanical society of Bengal, and can be contacted at [email protected]