Free Step 1-style question
Pregnant patient with megaloblastic anemia and no neurologic deficits; tests identification of the impaired folate-dependent reaction.
A 27-year-old woman in her second trimester is evaluated for progressive fatigue and exertional dyspnea. She has had poor oral intake due to persistent nausea throughout pregnancy. Examination shows conjunctival pallor and a smooth erythematous tongue, with normal vibration sense and normal gait. Peripheral blood smear shows macro-ovalocytes and hypersegmented neutrophils.
| Test | Value | Reference range |
|---|---|---|
| Hemoglobin | 9.7 g/dL | 12.0–15.5 g/dL |
| Mean corpuscular volume | 113 fL | 80–100 fL |
Which of the following biochemical reactions is most directly impaired in this patient?
- A. Conversion of deoxyuridylate to thymidylate
- B. Conversion of homocysteine to cystathionine
- C. Conversion of methylmalonyl-CoA to succinyl-CoA
- D. Conversion of phenylalanine to tyrosine
- E. Conversion of pyruvate to oxaloacetate
Correct answer: A. Conversion of deoxyuridylate to thymidylate
Megaloblastic anemia with macro-ovalocytes and hypersegmented neutrophils, glossitis, and poor dietary intake during pregnancy in the absence of posterior column neurologic findings is most consistent with folate deficiency. Folate is reduced to tetrahydrofolate derivatives that carry one-carbon units used in nucleotide synthesis. In thymidylate synthesis, 5,10-methylene tetrahydrofolate supplies a one-carbon unit during thymidylate synthase conversion of deoxyuridylate to deoxythymidylate. Folate deficiency impairs this reaction, reducing dTMP availability for DNA synthesis and causing ineffective erythropoiesis with macro-ovalocytes and hypersegmented neutrophils.
Takeaway
Folate deficiency impairs tetrahydrofolate-dependent one-carbon transfer reactions, especially thymidylate synthase conversion of deoxyuridylate to thymidylate. Unlike vitamin B12 deficiency, folate deficiency does not impair methylmalonyl-CoA mutase or increase methylmalonic acid.
What this page covers
Practice Step 1-style biochemistry questions on Folate deficiency, with emphasis on enzyme / mechanism and answer-choice reasoning.
Step 1 practice focus
This preview is organized around Folate deficiency in Water-Soluble Vitamins within Vitamins & Cofactors. It is intended for students practicing enzyme / mechanism questions, where the goal is to connect the vignette clue pattern to the underlying biochemical pathway, enzyme defect, metabolite change, regulatory step, or physiologic consequence.
How to use this page
Review the topic and reasoning focus, then practice Step 1-style questions inside BiochemStep. The question set emphasizes mechanism-first answer-choice reasoning rather than passive content review.