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Speciation of aluminum in biological systems

TitleSpeciation of aluminum in biological systems
Publication TypeJournal Article
Year of Publication1996
AuthorsHarris, WR, Berthon, G, Day, JP, Exley, C, Flaten, TP, Forbes, WF, Kiss, T, Orvig, C, Zatta, PF
JournalJournal of Toxicology and Environmental Health
Volume48
Pagination543-568
Date PublishedAug
Type of ArticleProceedings Paper
ISBN Number0098-4108
KeywordsALZHEIMERS-DISEASE, DIETARY CONSTITUENTS, DRINKING-WATER, GASTROINTESTINAL ABSORPTION, HUMAN-SERUM TRANSFERRIN, MURINE, NEUROBLASTOMA-CELLS, POTENTIAL, PROTEIN-BINDING, SIGNIFICANCE INVIVO, SIZE-EXCLUSION CHROMATOGRAPHY, THERAPEUTIC CHELATING-AGENTS
Abstract

As a ’’hard’’ trivalent metal ion, Al3+ binds strongly to oxygen-donor ligands such as citrate and phosphate. The aqueous coordination chemistry of Al is complicated by the tendency of many Al complexes to hydrolyze and form polynuclear species, many of which are sparingly soluble. Thus there is considerable variation among the Al stability constants reported for several important ligands. The complexity in the aqueous chemistry of Al has also affected Al toxicity studies, which have often utilized poorly characterized Al stock solutions. Serum fractionation studies show that most Al is protein bound, primarily to the serum iron transport protein transferrin. Albumin appears to play little, if any, role in serum transport. There is little agreement as to the speciation of the remaining low-molecular-mass fraction of serum Al. The lability of the Al3+ ion precludes the simple separation and identification of individual Al complexes. Computational methods are available for detailed computer calculations of the Al speciation in serum, but efforts in this area have been severely hampered by the uncertainties regarding the stability constants of the low molecular mass Al complexes with Citrate, phosphate, and hydroxide. Specific recommendations for further research on Al speciation include: (1) Determine more accurate Al stability constants with critical low molecular mass ligands such as citrate and phosphate; (2) supplement traditional potentiometric studies on Al complexes with data from other techniques such as Al-27-NMR and accelerator mass spectrometry with Al-26; (3) develop new methods for generating reliable linear free energy relationships for Al complexation; (4) determine equilibrium and rate constants for Al binding to transferrin al 37 degrees C; (5) confirm the possible formation of low-molecular-mass Al-protein complexes following desferrioxamine therapy; (6) continue research efforts to incorporate kinetic considerations into the present equilibrium speciation calculations; (7) improve methods for preparing chemically well-defined stock solutions for toxicological studies; (8) incorporate more detailed speciation data into studies on Al toxicity and pharmacokinetics; and (9) incorporate more detailed speciation data into future epidemiological studies on the relationship between Al toxicity and various water quality parameters.

URL<Go to ISI>://A1996VE14400005