Question

Which of the following statement(s) is/are true about the Type IV isozyme of the hexokinase?
(A). It is highly specific for glucose and is thus often called as glucokinase.
(B). It has much higher \( K_m \) value for glucose
(C). It is allosterically inhibited by glucose-6-phosphate
(D). It is a non-inducible enzyme and follows Michaelis-Menten Kinetics

Choose the correct answer from the options given below:

• A. (A), (B) and (D) only.
• B. (A) and (B) only.
• C. (A), (C) and (D) only.
• D. (A) and (D) only.

Hint:

Remember that glucokinase (Hexokinase IV) acts as a systemic glucose sensor.
Its high \( K_m \) (low affinity) and lack of feedback inhibition by glucose-6-phosphate allow it to function effectively in clearing glucose from the blood after a meal.

Answer 1

The Correct Option is B

Step 1: Understanding the Concept:
Hexokinase catalyzes the first step of glycolysis: the phosphorylation of glucose to glucose-6-phosphate.
Mammalian tissues contain four major isozymes of hexokinase (Types I–IV).
Hexokinase IV, commonly known as glucokinase, is structurally and kinetically distinct from Types I–III and is expressed primarily in the liver and pancreatic \( \beta \)-cells to regulate systemic blood glucose levels.

Step 2: Detailed Explanation:
Let us evaluate each of the four statements regarding Hexokinase IV (glucokinase):
- Statement (A) is true: Glucokinase is highly selective for D-glucose over other hexose sugars (like fructose or mannose), which is why it is called glucokinase.
- Statement (B) is true: Glucokinase exhibits a relatively high \( K_m \) for glucose (approximately \( 10\text{ mM} \)), which is significantly higher than the physiological blood glucose concentration (typically \( 4 \text{ to } 5\text{ mM} \)).
In contrast, Hexokinases I–III have a very low \( K_m \) (less than \( 0.1\text{ mM} \)) and operate at maximum velocity even at low blood glucose levels.
The high \( K_m \) of glucokinase allows its rate of reaction to change proportionally with changes in blood glucose levels.
- Statement (C) is false: Hexokinases I–III are allosterically inhibited by their product, glucose-6-phosphate.
Glucokinase is completely insensitive to physiological concentrations of glucose-6-phosphate, enabling the liver to continue phosphorylating and storing glucose as glycogen even when intracellular glucose-6-phosphate concentrations are high.
- Statement (D) is false: Glucokinase is an inducible enzyme whose transcription is regulated by insulin.
Furthermore, it displays cooperative, sigmoidal kinetics with respect to glucose rather than standard hyperbolic Michaelis-Menten kinetics.
Therefore, only statements (A) and (B) are correct.

Step 3: Final Answer:
The correct option is (B), as only statements (A) and (B) are true.