Absorbed Al(III) is transported by the bloodstream. Different speciation models [15,20,63,64] have been reported in the literature, in connection with the actual chemical forms of Al(III) in the blood serum. As concerns the protein fraction, all models agree that most of the Al(III) is bound to transferrin. Albumin, another potential carrier protein, is a much weaker metal ion binder and is not assumed to be able to compete for a significant amount of Al(III) [9,65]. The picture is much more controversial as concerns the more mobile l.m.m. Al(III) binders [15,20,63,64]. The reason is the lack of reliable speciation data. In the Al(III)-phosphate system, under model conditions in the mM concentration range, precipitation occurs at pH > 3.5, but extrapolation from the experimental data to physiological conditions may be rather dangerous .
Further, there are rather slow oligomerization reactions in the Al(III)-citrate system, which are strongly concentration-dependent. At mM concentrations, a trinuclear species [Al3(CitH_1)3(OH)]4- predominates in a wide pH range including the physiological pH, in a thermodynamic equilibrium state . This trinuclear complex is formed, in a rather slow process, via the interactions of mononuclear 1:1 and 1:2 complexes, which exist at the beginning of complex formation and also predominate at high excesses of the ligand . Electrospray ionization mass spectrometry (ESI-MS) measurements have proved that the halflife of formation of the trinuclear species at about 10 ^M Al(III) is ~80 min . It is reasonable to question whether the thermodynamic equilibrium approach provides a realistic description of the Al(III) speciation under physiological conditions: when the Al(III) concentration rarely exceeds a few ^M, the ligand excess for potential binders is at least 1000- to 10,000-fold, and, in consequence of the continuous metabolism, biological fluids are open systems, which never reach true thermodynamic equilibrium. The problem of time-dependent specia-tion is a real challenge in Al(III) bioinorganic chemistry .
Harris et al.  used difference UV spectroscopy as the basic method, supported by pH-metric and ESI-MS measurements. They reported a model for the biospeciation of Al(III) in serum at ~10 ^M Al(III), which is much closer to the biologically relevant value, ~01-0.3 ^M [66,67]. Their speciation model (Table 2) indicates that 93% of the total Al(III) is bound to transferrin. Of the pool of l.m.m. Al, 88% would be bound to citrate, 8% to hydroxide and only ~2% to phosphate .
The speciation models reported so far ignored the formation of ternary complexes between citrate and phosphate. Recently, the time-dependent speciation in the Al(III)-citrate (A3-)-phosphate (B3-) ternary system has been monitored by pH-potentiometry and multinuclear NMR spectroscopy . Table 2 presents the species distribution of Al(III) under plasma conditions. At physiological pH, phosphate seems to be the more efficient Al(III) binder, although citrate-bound Al(III) also occurs in significant concentration, in accordance with the results of Bell et al. , who detected Al(III)-bound citrate in native serum by means of :H NMR. Bantan et al.  studied the speciation of l.m.m. Al(III) complexes in serum from healthy volunteers by means of fast liquid chro-matography and electrospray techniques. In agreement with the results discussed
Speciation of Al(III) with blood serum components at pH ~7.4 and 25 °C.
% of Al(III) bound Cai(iii) = 10 M-M  CAl(ni) = lmM 
High molecular mass components Albumin Transferrin
Low molecular mass components Phosphate Citrate
above , they found that the main l.m.m. Al(III) species present in the serum are binary Al(III)-citrate, Al(III)-phosphate and ternary Al(III)-citrate-phosphate complexes. The distribution of these complexes varied from individual to individual.
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