I am going to answer the sample USMLE Step 1 Questions with Explanation. These questions are available at USMLE.org
A 60-year-old man comes to the office because of weakness, tingling of his hands and feet, irritability, and forgetfulness for 4 months. Physical examination shows pallor, weakness, and spasticity. Deep tendon reflexes are increased. Sensation to vibration is absent in the lower extremities. Laboratory studies show megaloblastic anemia, serum antiparietal cell antibodies, and increased serum concentrations of methylmalonic acid and total homocyst(e)ine. The synthesis of which of the following amino acids is most likely impaired in this patient?
(A) Cysteine
(B) Glutamine
(C) Methionine
(D) Phenylalanine
(E) Tyrosine
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Answer
This patient likely has vitamin B12 deficiency, which can present with neurological symptoms (such as weakness, tingling, irritability, and forgetfulness), megaloblastic anemia, and elevated methylmalonic acid and homocysteine levels.
Vitamin B12 is a cofactor for two critical reactions:
- Methylmalonyl-CoA → Succinyl-CoA (via methylmalonyl-CoA mutase)
- Homocysteine → Methionine (via methionine synthase, which also requires folate)
The elevated methylmalonic acid suggests that the first reaction is impaired, and the elevated homocyst(e)ine indicates impaired conversion of homocysteine to methionine.
Therefore, the synthesis of methionine is impaired in this patient.
The correct answer is: (C) Methionine.
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