Non-Equilibrium Binding of Aluminium in Biological Systems

Fact: Ninety-percent of the aluminium in the blood is bound to the iron transport protein transferrin.

Or is it?

The truth of the matter is that all we know for sure, is that by the time a measurement has been taken, 90% of the aluminium in our sample of serum sitting in a test-tube at thermodynamic equilibrium, has been complexed with transferrin. Is that a true representation of the complex situation of whole blood in vivo? If we were to use some sort of "super camera" to take a snapshot of the distribution of Al in whole blood in vivo, to which ligands would it be bound? Would this distribution really be identical to that observed in a test tube?

We have used ground-up, Markov-chain Monte Carlo computational simulation methods to investigate how the distribution of aluminium in a  biological medium such as blood, might change through time as it progresses to its ultimate fate (fixation or excretion).

aluminium transferrin and citrate simulation

After the introduction of Al to the bloodstream (time T=0), its instantaneous distribution amongst its various potential ligands at time T some point later determines where it is possible for it to be transported. Further insight therefore may give clues as to the nature of aluminium distribution, deposition and toxicity, and give insight into new methods for relieving toxicity.

To find out more, please check out the following references:

  1. Exley C, Beardmore J, Rugg G (2007) Computational Approach to the Blood Aluminium Problem?, International Journal of Quantum Chemistry, vol. 107, pp.275-278.
  2. Beardmore J, Rugg G & Exley C (2007) A systems biology approach to the blood-aluminium problem: The application and testing of a computational model. Journal of Inorganic Biochemistry, vol. 101, issue 9, pp.1187-1191.
  3. Beardmore J & Exley C (2009) Towards a model of non-equilibrium binding of metal ions in biological systems. Journal of Inorganic Biochemistry, vol. 103, pp.205-209.