Question

The blood glucose concentration is controlled by the liver. It removes glucose from the blood stream and stores it when the blood glucose concentration gets too high and it releases glucose to the blood stream when its concentration gets too low. Unlike HK II, it needs to be able to respond to a range of glucose concentrations. As a result, hexokinase activity in liver has a different concentration dependence profile compared to HK II in muscle—HK IV is NOT a Michaelis-Menten enzyme.

1. Given its role, how would you expect the rate vs. [glucose] plot to look for hexokinase in liver? Sketch it below. (Consider another protein that we discussed that has to respond to a range of different ligand concentrations) "

Answer 1

The liver function in buffering the blood glucose level is made possible by the enzyme glucokinase also known as hexokinase-IV or hexokinase D. The hexokinases present in other cell obey the Michaelis-Menten kinetics as they have a high glucose affinity (Km<0.1mM) but the glucokinase present in liver has a Kmof approximately 5mM that is it has low affinity for glucose. And display a sigmoidal kinetics with a Hill constant of 1.5. The advantage of this phenomenon is that the normal hexokinase is inhibited by Glucose-6-phosphate and when the blood glucose level is high, hexokinase-II will rapidly break down glucose and produce glucose-6-phosphate which will inturn inactivate the enzyme. But on the other hand hexokinase-IV has a low affinity towards glucose and will only be active at higher concentrations and it is not also inhibited by Glucose-6-phosphate. Thus the higher the blood glucose the faster liver converts glucose to G6P by glucokinase. And the hexokinase-II will be active when the bolld glucose concentration will not be that high or in othher tissue than liver.

The glucokinase curve is generated using Hill equation with K=10mM and n=1.5.