The speciation of vanadium in human serum

A knowledge of the speciation of vanadium in human serum is essential for an understanding of the biotransformation of antidiabetic vanadium complexes in human blood and of how vanadium is transported to the target cells. Such information may be acquired by two completely different approaches: separation techniques and modeling calculations. This review focuses on the latter. The two major metal ion binders in human serum are apotransferrin (apoTf) and human serum albumin (HSA), the interactions of which with (VO)-O-IV and V-V are discussed in detail. A partially new model for HSA-(VO)-O-IV interactions is introduced, in which the two binding sites (one for two and one for one metal ion) compete not only with each other, but also with hydrolysis of the metal ion. Focus is also placed on the possibility and importance of ternary complex formation between (VO)-O-IV, serum proteins and drug candidate ligands (maltol (mal), 1,2-dimethy1-3-hydroxy-4(1H)-pyridinone (dhp), acetylacetone (acac) and picolinic acid, (pic)): the structures and formation constants of different ternary complexes reported by the different research groups are critically reviewed. The serum speciations for (VO)-O-IV and V-V are calculated through use of the most recent stability constants; at biologically relevant concentrations (similar to 1 mu M, but definitely <10 mu M) the apoTf complexes predominate for both metal ions. This has the consequences that the primary role of the drug candidate ligands of the original complexes is a carrier function until the vanadium is taken up into the serum, and the vanadium ion itself is the active metabolite responsible for the antidiabetic effect. (C) 2011 Elsevier B.V. All rights reserved.