Lead poisoning inhibits two enzymes in heme synthesis, causing accumulation of ALA and zinc protoporphyrin (ZPP). The two enzymes inhibited by lead are:

• A ALA synthase and ferrochelatase
• B Porphobilinogen deaminase and uroporphyrinogen decarboxylase
• C Coproporphyrinogen oxidase and protoporphyrinogen oxidase
• D ALA dehydratase and ferrochelatase ✓

Explanation

Lead inhibits ALA dehydratase (also called porphobilinogen synthase) which condenses 2 ALA → PBG, causing urine ALA elevation. Lead also inhibits ferrochelatase (the final enzyme inserting Fe2+ into protoporphyrin IX). With ferrochelatase blocked, zinc (present in higher concentration than iron in cytoplasm of erythrocyte precursors) is inserted instead, forming zinc protoporphyrin (ZPP). ZPP is the basis of the ZPP test for lead exposure. Clinically, urine ALA and coproporphyrin III are elevated while PBG is not elevated (unlike the acute porphyrias). Basophilic stippling of RBCs results from ribosomal aggregation caused by inhibition of 5'-nucleotidase by lead.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.