Nucleotide metabolism: trimethoprim selectivity: 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 · Nucleotide metabolism: trimethoprim selectivity

Sample item

Trimethoprim blocks nucleotide synthesis in bacteria but is relatively safe for human cells. Which property accounts for this selectivity?

AIt binds bacterial dihydrofolate reductase far more tightly than the human enzymeBIt cannot enter human cells, which lack folate carriersCIt is activated only by bacterial thymidine kinaseDIt inhibits dihydropteroate synthase, found only in bacteria

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

The answer and the reasoning

A. It binds bacterial dihydrofolate reductase far more tightly than the human enzyme

Trimethoprim is a folate analogue with far higher affinity for bacterial dihydrofolate reductase than for the human enzyme. Blocking the bacterial enzyme depletes tetrahydrofolate and so thymidylate and purines.

Option by option

A. It binds bacterial dihydrofolate reductase far more tightly than the human enzyme (correct)
Correct. Its affinity for the bacterial reductase is far higher than for the human one.
B. It cannot enter human cells, which lack folate carriers
Human cells have folate carriers, and entry of the drug is not the basis of selectivity.
C. It is activated only by bacterial thymidine kinase
Trimethoprim does not need activation by a thymidine kinase.
D. It inhibits dihydropteroate synthase, found only in bacteria
Dihydropteroate synthase is the target of sulfonamides, not trimethoprim.

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, It binds bacterial dihydrofolate reductase far more tightly than the human enzyme. Trimethoprim is a folate analogue with far higher affinity for bacterial dihydrofolate reductase than for the human enzyme.

Why is "It cannot enter human cells, which lack folate carriers" not the answer?

Human cells have folate carriers, and entry of the drug is not the basis of selectivity.

Why is "It is activated only by bacterial thymidine kinase" not the answer?

Trimethoprim does not need activation by a thymidine kinase.

Why is "It inhibits dihydropteroate synthase, found only in bacteria" not the answer?

Dihydropteroate synthase is the target of sulfonamides, not trimethoprim.

What concept does this question test?

It tests Nucleotide metabolism: trimethoprim selectivity in Biochemistry. Blocking the bacterial enzyme depletes tetrahydrofolate and so thymidylate and purines.

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 Nucleotide metabolism: trimethoprim selectivity?

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.