Lead is particularly harmful to the body because it mimics metal ions, thus interfering with membrane proteins.6 Calcium is essential for initiating many signaling pathways. When lead binds instead of calcium, the signaling pathway is interrupted.6 This affects the nervous system because synaptic transmission is often one of these interrupted pathways.13 When lead interrupts this pathway, signaling molecules called neurotransmitters cannot communicate with target cells across the synapse. This causes a cascade of negative effects in both the nervous system and the body as a whole.
Free Radicals and Oxidative Stress
Normally there is a homeostatic balance between antioxidant defense and free radicals.15 Lead exposure interrupts this homeostasis and causes oxidative stress and eventually, cell death.16 Some consequences of oxidative stress include lipid peroxidation, protein alteration and loss of function, and genotoxicity. Lead’s inhibition of δ-Aminolevulinic Acid Dehydratase (ALAD) causes the heme precursor, δ-aminolevulinic acid (ALA), to accumulate.26 This molecule can auto oxidize, causing more free radical species to be released.29 Oxidative stress associated with ALA can disrupt the activity of the neurotransmitter GABA.33 Also, lead disrupts the function of antioxidants, exacerbating the oxidative stress.
As aforementioned, lead inhibits δ-aminolevulinic acid dehydratase (ALAD). This is an enzyme that binds to the substrate δ-aminolevulinic acid (ALA) to produce a heme precursor.38 Normally, ALAD function is assisted by zinc in the metal binding site. When lead is present, it displaces zinc from the binding site.27 Once it has displaced zinc, lead takes on a different configuration than zinc does in the binding site due to its lone pair.40 This discrepancy could disrupt binding interactions between ALAD and its substrate ALA, the enzyme is inhibited and the heme synthesis pathway cannot continue.45 The associated ALA accumulation is harmful for the nervous system because it causes oxidative stress, disrupts GABA function, and a variety of other neurovisceral symptoms.29
This and the other summary page about the recent research are a nice touch