1.
Glucokinase phosphorylates glucose in liver only when glucose levels are higher than
normal. What property of glucokinase is responsible for this?
a. High molecular weight
b. High Km
c. High Vmax
d. Ability to act equally on D- and L-glucose
Glucokinase High Km Liver Glucose Phosphorylation Explained
Glucokinase phosphorylates glucose specifically in the liver during high glucose conditions due to its unique kinetic properties. The correct answer is b. High Km. This high Km value ensures glucokinase remains inactive at normal blood glucose levels (~5 mM), activating only when glucose exceeds this threshold post-meal.
Option Analysis
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a. High molecular weight: Incorrect. Glucokinase has a molecular weight of ~50 kDa, lower than hexokinases I-III (~100 kDa). This size difference relates to domain structure but does not control glucose level sensitivity.
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b. High Km: Correct. Glucokinase’s Km (~5-10 mM) matches postprandial blood glucose, indicating low glucose affinity. Unlike hexokinase (low Km ~0.1 mM), it functions as a “glucose sensor,” phosphorylating excess glucose for storage without competing at normal levels.
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c. High Vmax: Partially true but irrelevant. Glucokinase has high Vmax for high-capacity glucose processing, yet this does not explain activation threshold—Km determines that.
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d. Ability to act equally on D- and L-glucose: Incorrect. Glucokinase is D-glucose specific, with higher activity on β-D-glucose than α-D-glucose; it does not act on L-glucose.
Glucokinase high Km liver glucose phosphorylation acts as a metabolic switch, ensuring the liver stores excess glucose as glycogen only after meals when blood levels rise above 5 mM. This property distinguishes it from hexokinase, preventing unnecessary glucose trapping during fasting.
Glucokinase vs Hexokinase Kinetics
| Property | Glucokinase (Liver) | Hexokinase (Other Tissues) | Functional Impact |
|---|---|---|---|
| Km for Glucose | High (~5-10 mM) | Low (~0.1 mM) | Activates only at high glucose; spares glucose for brain/RBCs |
| Vmax | High | Low | High-capacity storage post-meal |
| Inhibition | Not by G6P | By G6P | Sustained activity in fed state |
| Location | Liver, β-cells | Most tissues | Liver buffers blood glucose |
Physiological Role in Glucose Homeostasis
Glucokinase’s high Km aligns with physiological glucose (normal: 4-5.5 mM; post-meal: >7 mM), promoting glycolysis and glycogen synthesis during fed states while glucagon represses it in fasting. Mutations lowering activity cause MODY2 diabetes with mild hyperglycemia.
This mechanism supports CSIR NET concepts in biochemistry, linking enzyme kinetics to metabolic regulation across cell biology and physiology.
