Lead with a poisonous electron shield

Jan 16, 2007

It has been speculated that lead poisoning may have played a role in the fall of the Roman Empire: it is thought to have been caused by the concentration of grape juice in lead containers. Though the introduction of lead-free gasoline has reduced damage to the environment, the annual production of lead continues to increase worldwide because lead is still used in batteries, glass, and electronic components.

However, there has thus far been little research into what, at a molecular level, causes the toxic effects of lead. French researchers have now applied quantum chemistry to very simple enzyme models and gained new insights. As they have reported in Angewandte Chemie, it seems that the lead's "electron shield" is the main culprit.

Lead does the most damage to the nervous system, kidneys, liver, brain, and blood. These kinds of damage are especially severe for children as they can be irreversible. Complexation agents that grab onto the metal cations are used as antidotes. However, these agents are not lead-specific, meaning that they also remove other important metal cations from the body.

C. Gourlaouen and O. Parisel (Laboratoire de Chimie Théorique, Université Paris 6) took a closer look at two proteins to which lead likes to bind. Calmodulin, a calcium-binding protein, plays an important role in regulating and transporting the calcium cation in the human body. A calcium ion binds to seven ligands at the active centers of the enzyme. If one of the four possible calcium ions of calmodulin is replaced by lead, the lead ion remains roughly heptacoordinated, but this active center becomes distorted and inefficient; the three remaining sites get a reduced efficiency.

d-Aminolevulinic acid dehydratase is essential for the biosynthesis of hemoglobin. Inhibition of this enzyme disrupts the formation of blood to the point of anemia. At the active center, a zinc ion binds to four ligands, three of which involve a sulfur atom. When lead replaces zinc, it only binds to the three sulfur atoms. The reason for this is the emerging free electron pair of the lead cation. It acts as an electronic shield on one side, pushing away the fourth ligand. Such a dramatic geometrical distortion at the active center could explain why lead inhibits this enzyme.

The different behavior of lead in these two enzymes demonstrates that it can enter into complexes in which the metal–ligand bonds can either point in all directions, or into only one hemisphere, while the other hemisphere is filled by the free electron pair. This observation may help in the design of future lead-specific antidotes.

Citation: Olivier Parisel, Is an Electronic Shield at the Molecular Origin of Lead Poisoning? A Computational Modeling Experiment, Angewandte Chemie International Edition 2007, 46, No. 4, 553–556, doi: 10.1002/anie.200603037

Source: John Wiley & Sons

Explore further: New technique reveals immune cell motion through variety of tissues

add to favorites email to friend print save as pdf

Related Stories

Cells build 'cupboards' to store metals

Dec 17, 2014

Lawrence Livermore researchers in conjunction with collaborators at University of California (link is external), Los Angeles have found that some cells build intracellular compartments that allow the cell ...

Scientists find key to vitamin A metabolism

Dec 10, 2014

Researchers at Case Western Reserve University School of Medicine have uncovered the mechanism that enables the enzyme Lecithin: retinol acyltransferase (LRAT) to store vitamin A—a process that is indispensable ...

Discovery links shift in metabolism to stem cell renewal

Dec 10, 2014

Stem cells in early embryos have unlimited potential; they can become any type of cell, and researchers hope to one day harness this rejuvenating power to heal disease and injury. To do so, they must, among ...

Recommended for you

'Global positioning' for molecules

Dec 19, 2014

In everyday life, the global positioning system (GPS) can be employed to reliably determine the momentary location of one en route to the desired destination. Scientists from the Institute of Physical and ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.