Javed H Hussain
Children’s Hospital, Boston; Harvard Medical School, 300, Longwood Ave, Boston, MA 02215, USA. firstname.lastname@example.org
No other heavy metal toxicity has gained as much public attention as lead – due to its impact on the developing brain of young children. Lead is ubiquitous in our environment but has no physiologic role in our biological systems. Lead became part of our daily life due to its easy workability, low melting point and corrosion-resistance. Later in our industrial society, it became part of house paint due its shining and lasting function and also used in gasoline for its anti-knock properties.
The toxicity of lead comes from its ability to mimic other biologically important metals, most notably calcium, iron and zinc, which act as cofactors in many enzymatic reactions. Lead is able to bind to enzymes delta-aminolevulinic acid dehydratase, and ferrochelatase, affecting the biosynthesis of heme causing anemia.
Lead also interferes with excitatory neuro-transmission by glutamate, which is the transmitter at more than half the synapses in the brain and is critical for learning. N-methyl-D-aspartate (NMDA) receptor, thought to be associated with neuronal development and plasticity, is blocked selectively by lead. This disrupts long-term potentiation, which compromises the permanent retention of newly learned information(1). Lead exposure also decreases the amount of NMDA receptor gene and protein in hippocampus(2).