Biomolecules and enzymes: substrate reduction therapy in Gaucher disease: 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 · Biomolecules and enzymes: substrate reduction therapy in Gaucher disease

Sample item

An adult with type 1 Gaucher disease is given an oral drug such as eliglustat that does not replace the missing enzyme. Instead it lowers production of the lipid that accumulates in macrophages. Which enzyme does it inhibit?

AGalactocerebrosidaseBCeramidaseCSphingomyelinaseDGlucosylceramide synthase

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

The answer and the reasoning

D. Glucosylceramide synthase

In Gaucher disease glucocerebrosidase deficiency causes glucosylceramide to accumulate. Substrate reduction therapy (eliglustat, miglustat) inhibits glucosylceramide synthase, which makes the first step of the glucosphingolipid pathway, so less substrate reaches the defective step.

Option by option

A. Galactocerebrosidase
Galactocerebrosidase is the deficient enzyme in Krabbe disease and is not the target of these drugs.
B. Ceramidase
Ceramidase breaks down ceramide and is the deficient enzyme in Farber disease.
C. Sphingomyelinase
Sphingomyelinase breaks down sphingomyelin and is the deficient enzyme in Niemann-Pick A and B.
D. Glucosylceramide synthase (correct)
Correct. Inhibiting glucosylceramide synthase reduces the amount of lipid that must be degraded.

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, Glucosylceramide synthase. In Gaucher disease glucocerebrosidase deficiency causes glucosylceramide to accumulate.

Why is "Galactocerebrosidase" not the answer?

Galactocerebrosidase is the deficient enzyme in Krabbe disease and is not the target of these drugs.

Why is "Ceramidase" not the answer?

Ceramidase breaks down ceramide and is the deficient enzyme in Farber disease.

Why is "Sphingomyelinase" not the answer?

Sphingomyelinase breaks down sphingomyelin and is the deficient enzyme in Niemann-Pick A and B.

What concept does this question test?

It tests Biomolecules and enzymes: substrate reduction therapy in Gaucher disease in Biochemistry. Substrate reduction therapy (eliglustat, miglustat) inhibits glucosylceramide synthase, which makes the first step of the glucosphingolipid pathway, so less substrate reaches the defective step.

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 Biomolecules and enzymes: substrate reduction therapy in Gaucher disease?

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.