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

A drug blocks the pathway that supplies farnesyl pyrophosphate. Cells lose not only sterols but also ubiquinone, dolichol and the isoprenyl anchors of Ras-family proteins, because all arise from one early rate-limiting step. Which enzyme does the drug inhibit?

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

The answer and the reasoning

D. HMG-CoA reductase

The mevalonate pathway branches at farnesyl pyrophosphate into sterols, ubiquinone, dolichol and prenylated proteins. Blocking it at its first committed step reduces all branches, which may explain some statin side effects such as myopathy. Blocking squalene synthase would spare the non-sterol branches.

Option by option

  • A. Lanosterol demethylase

    Lanosterol demethylase acts after squalene cyclisation and affects only sterol synthesis.

  • B. Squalene synthase

    Squalene synthase lies beyond the branch point and would block sterols while sparing ubiquinone, dolichol and prenylation.

  • C. Acyl-CoA cholesterol acyltransferase

    Acyl-CoA cholesterol acyltransferase esterifies cholesterol and does not supply isoprenoids.

  • D. HMG-CoA reductase (correct)

    Correct. Inhibition at the first committed step lowers all products of the mevalonate pathway.

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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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is D, HMG-CoA reductase. The mevalonate pathway branches at farnesyl pyrophosphate into sterols, ubiquinone, dolichol and prenylated proteins.

Why is "Lanosterol demethylase" not the answer?

Lanosterol demethylase acts after squalene cyclisation and affects only sterol synthesis.

Why is "Squalene synthase" not the answer?

Squalene synthase lies beyond the branch point and would block sterols while sparing ubiquinone, dolichol and prenylation.

Why is "Acyl-CoA cholesterol acyltransferase" not the answer?

Acyl-CoA cholesterol acyltransferase esterifies cholesterol and does not supply isoprenoids.

What concept does this question test?

It tests Cholesterol metabolism: HMG-CoA reductase in Biochemistry. Blocking it at its first committed step reduces all branches, which may explain some statin side effects such as myopathy. Blocking squalene synthase would spare the non-sterol branches.

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 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.