Lead toxicity is due to multiple effects. Lead binds and inhibits the enzyme delta-aminolevulinic dehydratase (ALAD). ALAD is one of the key enzymes needed for the synthesis of heme from porphyrin. When this enzyme is inhibited by lead, protoporphyrin levels increase and heme production diminishes. Because of this, the detection of protoporphyrins can serve as a marker for lead toxicity.
Lead can form covalent bonds with the sulfhydryl group of cysteine. Thus, lead can bind to many different proteins causing a myriad of biological effects. Although the biochemistry of lead toxicity is complex and involves many different proteins and enzymes, it can be said that toxicity is mainly due to the inhibition of heme synthesis and free-radical-mediated generation of oxidative stress. This leads to the dysfunction of major biomolecules (lipid, protein, and nucleic acids), resulting in hepatotoxicity, neurotoxicity, nephrotoxicity, and DNA damage (genotoxicity). Lead also increases apoptosis and impairs cell differentiation and maturation.
Children with lead poisoning can present with anemia, developmental delay, learning difficulties, fatigue, abdominal pain, vomiting, constipation, hearing loss, and seizures. In adults, signs include microcytic/hypochromic anemia, high blood pressure, muscle pain, difficulties with memory or concentration, abdominal pain, mood changes, reduced sperm count, and miscarriage.
