Defects in Haem Synthesis in Mammalian Tissues in Experimental Lead Poisoning and Experimental Porphyria

Abstract

1. The biochemical effects of experimental lead poisoning and experimental porphyria induced by allyl-isopropylacetamide have been compared in New Zealand White rabbits. 2. In lead poisoning there was an increase in urinary coproporphyrin excretion within 48 hr of the first dose of lead. Urinary δ-aminolaevulic acid excretion increased about 1 week later and urinary porphobilinogen excretion about 3 weeks later. 3. In lead-poisoned rabbits the activity of the enzyme δ-aminolaevulic acid dehydrase was impaired in the brain, liver, kidney and bone marrow. This inhibition was largely due to interference with the sulphydryl groups of the enzyme. 4. No inhibition of the enzyme haem synthetase could be detected in homogenates prepared from lead poisoned tissues but the addition of lead acetate in concentrations similar to those present in the original unhomogenized tissues produced marked inhibition. 5. There was no increase in either the δ-aminolaevulic acid or the porphobilinogen content of the brain in lead poisoning but the δ-aminolaevulic acid content of the liver, kidney and bone marrow, and the porphobiliogen content of the kidney were significantly increased. 6. Inhibition by lead of the enzymes δ-aminolaevulic acid dehydrase and haem synthetase may explain the biochemical abnormalities observed in lead poisoning. 7. In experimental porphyria the main enzyme abnormality found was a large increase in δ-aminolaevulic acid synthetase activity in the liver with increases in δ-aminolaevulic acid dehydrase activity in the liver and kidney.