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Biochemistry · Enzyme kinetics: glucokinase
Sample itemA 14-year-old girl has stable mild fasting hyperglycaemia of about 7 mmol/L with HbA1c 6.4%, no ketosis and a similar finding in her mother. Heterozygous glucokinase mutation is found. Which property normally lets this enzyme act as a beta-cell glucose sensor?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
B. High Km for glucose and no inhibition by glucose 6-phosphate
Glucokinase has a Km of about 10 mM and a sigmoidal response to glucose, so its activity rises in proportion to glucose across the physiological range. It is not inhibited by glucose 6-phosphate, so flux tracks glucose supply. Loss-of-function mutations (MODY 2) raise the glucose threshold for insulin release, producing mild stable hyperglycaemia that seldom needs drug treatment.
Option by option
A. Strong feedback inhibition by glucose 6-phosphate
Hexokinase, not glucokinase, is inhibited by glucose 6-phosphate.
B. High Km for glucose and no inhibition by glucose 6-phosphate (correct)
Correct. A high Km without product inhibition makes it track glucose concentration.
C. Low Km for glucose, so it is saturated at fasting glucose
A low Km describes hexokinase, which is saturated at normal glucose and cannot sense changes.
D. Activation by glucagon through phosphorylation
Glucagon does not activate glucokinase and instead reduces glycolysis in liver.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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