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

When cellular sterol content is high, an endoplasmic reticulum enzyme of the cholesterol pathway binds Insig, is ubiquitinated and is degraded, while SREBP-2 stays retained in the membrane. Which enzyme is being degraded?

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

The answer and the reasoning

B. HMG-CoA reductase

High sterol levels accelerate Insig-dependent ubiquitination and proteasomal degradation of the rate-limiting enzyme, and also block SREBP-2 processing so that its gene is transcribed less. Both arms lower synthesis when cholesterol is plentiful. The enzyme turns over with a half-life of a few hours.

Option by option

  • A. Lanosterol synthase

    Lanosterol synthase is not subject to Insig-mediated degradation.

  • B. HMG-CoA reductase (correct)

    Correct. Sterol-accelerated degradation of the rate-limiting enzyme is a major feedback mechanism.

  • C. HMG-CoA synthase

    The synthase is transcriptionally regulated by SREBP-2 but is not the enzyme degraded through Insig.

  • D. Squalene epoxidase

    Squalene epoxidase has its own slower, sterol-linked regulation but it is not the classic Insig 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.

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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is B, HMG-CoA reductase. High sterol levels accelerate Insig-dependent ubiquitination and proteasomal degradation of the rate-limiting enzyme, and also block SREBP-2 processing so that its gene is transcribed less.

Why is "Lanosterol synthase" not the answer?

Lanosterol synthase is not subject to Insig-mediated degradation.

Why is "HMG-CoA synthase" not the answer?

The synthase is transcriptionally regulated by SREBP-2 but is not the enzyme degraded through Insig.

Why is "Squalene epoxidase" not the answer?

Squalene epoxidase has its own slower, sterol-linked regulation but it is not the classic Insig target.

What concept does this question test?

It tests Cholesterol metabolism: HMG-CoA reductase in Biochemistry. Both arms lower synthesis when cholesterol is plentiful. The enzyme turns over with a half-life of a few hours.

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.