Cholesterol metabolism: HMG-CoA reductase: 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 · Cholesterol metabolism: HMG-CoA reductase

Sample item

Hepatic cholesterol synthesis shows a diurnal rhythm with a peak at night, which is why shorter-acting lipid-lowering tablets are advised in the evening. Activity of which rate-limiting enzyme peaks at that time?

AHMG-CoA reductaseBSqualene synthaseCLanosterol synthaseDMevalonate kinase

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

The answer and the reasoning

A. HMG-CoA reductase

The rate-limiting enzyme of cholesterol synthesis has maximal activity at night, so short-half-life inhibitors are taken in the evening. Drugs with long half-lives, such as atorvastatin and rosuvastatin, can be taken at any time. The rhythm reflects feeding and hormonal changes acting on the controlling enzyme.

Option by option

A. HMG-CoA reductase (correct)
Correct. The rate-limiting enzyme peaks at night, which is why evening dosing suits short-acting inhibitors.
B. Squalene synthase
Squalene synthase acts after the branch point and is not the regulated step that timing of therapy is built around.
C. Lanosterol synthase
Lanosterol synthase cyclises squalene epoxide and is not rate-limiting.
D. Mevalonate kinase
Mevalonate kinase is feedback-inhibited by isoprenoids but is not the rate-limiting enzyme or drug target.

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 A, HMG-CoA reductase. The rate-limiting enzyme of cholesterol synthesis has maximal activity at night, so short-half-life inhibitors are taken in the evening.

Why is "Squalene synthase" not the answer?

Squalene synthase acts after the branch point and is not the regulated step that timing of therapy is built around.

Why is "Lanosterol synthase" not the answer?

Lanosterol synthase cyclises squalene epoxide and is not rate-limiting.

Why is "Mevalonate kinase" not the answer?

Mevalonate kinase is feedback-inhibited by isoprenoids but is not the rate-limiting enzyme or drug target.

What concept does this question test?

It tests Cholesterol metabolism: HMG-CoA reductase in Biochemistry. Drugs with long half-lives, such as atorvastatin and rosuvastatin, can be taken at any time. The rhythm reflects feeding and hormonal changes acting on the controlling enzyme.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. 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 Cholesterol metabolism: HMG-CoA reductase?

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.