In hepatocytes, glucokinase (hexokinase IV) differs from hexokinase I in several kinetic properties. Which property best explains why hepatic glucokinase functions as a glucose sensor during the fed state and remains active when blood glucose is high?

• A Low Km for glucose (1 mM) and strong product inhibition by glucose-6-phosphate
• B Low Km for glucose (1 mM) and allosteric activation by fructose-2,6-bisphosphate
• C High Km for glucose (10 mM) and strong inhibition by fructose-6-phosphate
• D High Km for glucose (10 mM) and no significant product inhibition by glucose-6-phosphate ✓

Explanation

Glucokinase has a high Km (~10 mM) for glucose, so it is active mainly when blood glucose is high (fed state). Unlike hexokinase I, it is not inhibited by glucose-6-phosphate, allowing continued glucose phosphorylation and glycogen/fatty acid synthesis. Option A describes hexokinase I. Options C and B list non-existent regulatory mechanisms for glucokinase.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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