Lead exposure inhibits which enzymes involved in heme synthesis?

• A. Ferrochelatase and ALA dehydratase
• B. Pyrimidine 5 nucleotidase
• C. Aminolevulinic acid synthase
• D. Glucose-6-phosphate dehydrogenase

Answer: (A)

Lead exposure disrupts heme synthesis by inhibiting two enzymes that act downstream in the pathway. After the first committed step forms delta-aminolevulinic acid (ALA), the next step converts ALA into porphobilinogen via ALA dehydratase, and a later step uses ferrochelatase to insert iron into protoporphyrin IX to form heme. When lead blocks these two enzymes, heme production falls, causing buildup of ALA upstream and, at the ferrochelatase block, accumulation of protoporphyrin substrates and reduced heme. This derailment explains the microcytic anemia and other related findings seen with lead poisoning. The other enzymes listed are not the targets of lead in this context: pyrimidine 5 nucleotidase and glucose-6-phosphate dehydrogenase are involved in nucleotide metabolism and the pentose phosphate pathway, not heme synthesis, and ALA synthase is the initial step and is not inhibited by lead (its activity may even be upregulated when heme is scarce).