A hypothesis for the basis of the pro-oxidant nature of calcium ions.
A new hypothesis describing the role of the redox inactive Ca2+ ion in the expression of physiological oxidative damage is described. The hypothesis is based on the optimization of the chelation characteristics of iron complexes for pro-oxidant activity. In a previous investigation it was found that an excess of ligand kinetically hindered the Fenton reaction activity of the FeII/III EDTA complex (Bobier et al. 2003). EDTA, citrate, NTA, and glutamate were selected as models for the coordination sites likely encountered by mobile iron, i.e. proteins. The optimal [EDTA]:[FeIII] ratio for Fenton reaction activity as measured by electrocatalytic voltammetry in a solution was found to be 1:1. An excess of EDTA in the amount of 10:1 [ligand]: [metal] suppresses the Fenton reaction activity to nearly the control. It is expected that the physiological coordination characteristics of mobile Fe would have a very large excess of [ligand]:[metal] and thus not be optimized for the Fenton reaction. Introduction of Ca2+ in to a ratio of 10:10:1 [Ca2+]:[EDTA]:[FeIII] to the system reinvigorated the Fenton reaction activity to nearly the value of the optimal 1:1 [EDTA] :[FeIII] complex. The pH distribution diagrams of Ca2+ in the presence of EDTA and FeII/III indicate that Ca2+ has the ability to uptake excess EDTA without displacing either FeII of FeIII from their respective complexed forms. The similarity in the presence for hard ligand sites albeit with a lower binding constant for Ca2+ accounts for this action.
Hutcheson
Ryan
R
Department of chemistry, University of Idaho, Moscow, ID 83844-2343, USA.
Engelmann
Mark D
MD
Cheng
I Francis
IF
D002118:Calcium / Q000378:metabolism*; D002384:Catalysis; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000737:chemistry; D004563:Electrochemistry; D018698:Glutamic Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D046911:Macromolecular Substances / Q000737:chemistry; D008956:Models, Chemical; D016877:Oxidants / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D011485:Protein Binding; D016897:Respiratory Burst
D002614:Chelating Agents; D008024:Ligands; D046911:Macromolecular Substances; D016877:Oxidants; D018698:Glutamic Acid; D004492:Edetic Acid; D002118:Calcium