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Physiology · Blood: haem synthesis
Sample itemA 45-year-old man on isoniazid for tuberculosis develops microcytic hypochromic anaemia with ring sideroblasts. Impairment of which haem synthesis step is responsible?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Condensation of glycine with succinyl CoA by ALA synthase, which needs pyridoxal phosphate
Haem synthesis begins in the mitochondrion with ALA synthase, the rate-limiting enzyme, combining glycine and succinyl CoA and needing pyridoxal phosphate (vitamin B6). Isoniazid depletes pyridoxal phosphate, so haem formation falls and iron accumulates in mitochondria around the nucleus, giving ring sideroblasts. Pyridoxine supplementation prevents this.
Option by option
A. Decarboxylation of uroporphyrinogen III, which needs folate
Uroporphyrinogen decarboxylase does not need folate.
B. Insertion of iron into protoporphyrin IX by ferrochelatase, which needs biotin
Ferrochelatase is inhibited by lead and does not need biotin as a cofactor.
C. Condensation of glycine with succinyl CoA by ALA synthase, which needs pyridoxal phosphate (correct)
Correct. Vitamin B6 deficiency impairs the committed first step.
D. Conversion of porphobilinogen to hydroxymethylbilane, which needs vitamin B12
Porphobilinogen deaminase does not need vitamin B12.
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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