Question

The binding definitive of cell surface receptor proteins is described by a parameter K0.5, which is analogous to K_M of an enzyme, and it represent the concentration of ligand where the protein is 50% saturated. Brain cells have a glucose binding receptor called GLUT3 and muscle cells have a similar receptor called GLUT4 on their membranes. Will the K0.5 of brain GLUT3 be higher or lower than the K0.5 of muscle GLUT4? What is the physiological significance of this difference?

Answer 1

K0.5 of GLUT3 is lower than K0.5 of GLUT4
K0.5 of GLUT3 is approximately 1.5mM and K0.5 of GLUT4 is about 5mM
Glucose is the major source of energy . Plasma membranes are impermeable to glucose like polar molecules and so their cellular uptake is done by special carrier proteins called glucose transporters. The glucose transporters is a family of 14 members .The most important among them are GLUT1, GLUT2, GLUT3, GLUT4 and GLUT5.

While comparing their k0.5 GLUT3 has lower than GLUT4
GLUT3 are mainly neuron specific because its proteins are mainly detected in the brain .Its mRNa are distributed in human tissues . It is a 496 residual protein and has 64% of GLUT1 and 52% of GLUT2 sequence identity, it also has GLUT1 similar transmembrane topology . It is a high affinity glucose transporter with km for glucose of around 2mM which is much less than the average blood glucose concentration (range 5 -7 mM).It enables most tissues to takeup glucose at constant rate regardless of amount present in blood.

GLUT4 - It is the only insulin responsive glucose transporter that has been identified . It is expressed predominantly in all insulin sensitive tissues .It transports glucose to muscle and fat cells. In the basal state this GLUT resides in intracellular compartment and is level is regulated by insulin. In the absence of insulin GLUT4 is sorted from the endosome to either
a) a perinuclear compartment or b) specialised GLUT4 storage vesicles.
Under basal conditions, cycling between the endosome and these two leads to retention of GLUT4 inside the cell.
When insulin binds to the insulin receptor it initiates a signaling cascade mechanism that causes translocation of GLUT4 to the plasma membrane. Fusion of GLUT4 storage vesicles with the plasma membrane in response to insulin results in greater amount of GLUT4 on the cell surface, and it leads to increased transport of glucose into the cell. Insulin signaling also inhibits GLUT4 endocytosis and thus results in longer duration of GLUT4 residence in the plasma membrane.