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Biochemistry · Vitamins: B12 and folate
Sample itemA strict vegan has macrocytic anaemia and paraesthesiae. His serum homocysteine and methylmalonic acid are both raised. What is the biochemical explanation for the neuropathy?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Accumulation of methylmalonyl-CoA with abnormal fatty acid incorporation into neuronal myelin
Vitamin B12 is the cofactor for methylmalonyl-CoA mutase and methionine synthase. Its deficiency raises methylmalonic acid and homocysteine. Methylmalonyl-CoA buildup is thought to cause abnormal odd-chain fatty acids in myelin, which accounts for neuropathy. Folate deficiency does not raise methylmalonic acid or cause neuropathy.
Option by option
A. Defective synthesis of the haem ring from glycine and succinyl-CoA
Haem synthesis from glycine and succinyl-CoA relates to ALA synthase and pyridoxine.
B. Reduced conversion of dUMP to dTMP by thymidylate synthase
Thymidylate synthase impairment explains megaloblastosis but is shared with folate deficiency and does not explain neuropathy.
C. Accumulation of methylmalonyl-CoA with abnormal fatty acid incorporation into neuronal myelin (correct)
Correct. Only B12 deficiency affects the mutase reaction and nerve myelin.
D. Failure of conversion of phenylalanine to tyrosine
Phenylalanine hydroxylase relates to phenylketonuria, not B12 deficiency.
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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