Aluminum-succinate complex equilibria and their potential implications for aluminum metabolism.

Apparent contradictory results have been reported about the effect of succinate on aluminum toxicity, distribution and excretion in mice. Investigating the influence of this ligand on aluminum speciation in the main biofluids may help understand the above observations at the molecular level. In the absence of experimental access to ultrafiltrable aluminum speciation, computer simulations have been used in the gastrointestinal fluid and blood plasma, based on Al-succinate complex formation constants determined under physiological conditions. Calculations run for gastrointestinal conditions show that Al-succinate soluble complexes are formed in the 2 to 6 pH range--especially the neutral M2L(OH)4--which may enhance aluminum absorption. This influence, however, should be limited by dietary phosphate. In blood plasma, there is no possibility for succinate to mobilize a significant aluminum fraction, which confirms a recent suggestion that the possible protective effect of succinate against aluminum toxicity in mice may not be due to aluminum complexation.

A new investigation of copper(II)-serine, copper(II)-histidine-serine, copper(II)-asparagine, and copper(II)-histidine-asparagine equilibria under physiological conditions, and implications for simulation models relative to blood plasma.

Some years ago, the application of computer modeling to metal speciation in biofluids was questioned based on the discrepancy between the simulated distribution of copper(II) in blood plasma and related experimental results obtained by Neumann and Sass-Kortsak in reconstituted serum. A recent investigation of the relevant copper(II)-amino acid equilibria reconciled these conflicting data, confirming that the reliability of computer models crucially depends on the data on which they are based. Since then, however, some of the constants of the copper-serine system used in that study have been suspected to be overestimated. This work thus reports the redetermination of copper-serine and copper-histidine-serine formation constants under physiological conditions. In addition, serine being close to asparagine in Neumann and Sass-Kortsak's classification, copper-asparagine and copper-histidine-asparagine equilibria have also been reinvestigated. For asparagine complexes, former constants have been basically confirmed. In contrast, all constants relative to serine have effectively been found lower than the previous ones. The effects of these new data on the stimulated distribution of plasma copper are only minor, but a better agreement is observed relative to Neumann and Sass-Kortsak's models in reconstituted serum.