Carbohydrate metabolism: glucokinase: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Carbohydrate metabolism: glucokinase

Sample item

A lean 17-year-old girl has asymptomatic fasting glucose values of 118 to 126 mg/dL on repeated testing, HbA1c 6.4% and negative islet autoantibodies. Her mother and maternal grandmother have the same mild hyperglycaemia. Which gene is most likely mutated?

AHNF1ABHNF1BCKCNJ11DGCK, encoding glucokinase

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

D. GCK, encoding glucokinase

Heterozygous inactivating mutations of glucokinase cause MODY2. Glucokinase is the pancreatic beta cell glucose sensor, with a high Km, so a higher glucose concentration is needed to trigger insulin release, resetting the fasting set-point to about 100 to 145 mg/dL. The hyperglycaemia is stable, complication-free and usually needs no drug treatment.

Option by option

A. HNF1A
HNF1A mutations cause progressive MODY3 with marked post-prandial rises that respond to sulfonylureas.
B. HNF1B
HNF1B mutations cause renal cysts and genital tract anomalies with diabetes.
C. KCNJ11
KCNJ11 activating mutations cause neonatal diabetes, not stable mild familial hyperglycaemia.
D. GCK, encoding glucokinase (correct)
Reduced glucokinase activity raises the glucose threshold for insulin secretion, giving stable mild hyperglycaemia inherited dominantly.

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.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is D, GCK, encoding glucokinase. Heterozygous inactivating mutations of glucokinase cause MODY2.

Why is "HNF1A" not the answer?

HNF1A mutations cause progressive MODY3 with marked post-prandial rises that respond to sulfonylureas.

Why is "HNF1B" not the answer?

HNF1B mutations cause renal cysts and genital tract anomalies with diabetes.

Why is "KCNJ11" not the answer?

KCNJ11 activating mutations cause neonatal diabetes, not stable mild familial hyperglycaemia.

What concept does this question test?

It tests Carbohydrate metabolism: glucokinase in Biochemistry. Glucokinase is the pancreatic beta cell glucose sensor, with a high Km, so a higher glucose concentration is needed to trigger insulin release, resetting the fasting set-point to about 100 to 145 mg/dL. The hyperglycaemia is stable, complication-free and usually needs no drug treatment.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Carbohydrate metabolism: glucokinase?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.