Which enzymes are affected by lead poisoning?

Lead poisoning primarily affects the heme synthesis pathway, specifically influencing the activity of two key enzymes: ALA dehydratase and ferrochelatase.

ALA dehydratase is responsible for condensing two molecules of aminolevulinic acid (ALA) to form porphobilinogen in the heme synthesis pathway. Lead inhibits this enzyme, leading to an accumulation of ALA, which is neurotoxic and can contribute to the symptoms observed in lead toxicity.

Ferrochelatase, on the other hand, catalyzes the insertion of iron into protoporphyrin IX to form heme. Lead exposure inhibits ferrochelatase as well, which results in decreased heme production and subsequently leads to the accumulation of protoporphyrins. This disruption causes the characteristic findings in lead poisoning, such as microcytic anemia due to impaired hemoglobin synthesis.

The consequences of lead's effect on these enzymes highlight its role in disrupting normal erythropoiesis and lead to the clinical manifestations associated with lead toxicity, including abdominal pain, neurological deficits, and the peripheral blood findings of basophilic stippling.