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The speciation of vanadium in human serum

机译:人血清中钒的形态

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A knowledge of the speciation of vanadium in human serum is essential for an understanding of the bio-transformation 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 V~ⅣO and V~Ⅴ are discussed in detail. A partially new model for HSA-V~ⅣO 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 V~ⅣO, serum proteins and drug candidate ligands (maltol (mal), 1,2-dimethyl-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 V~ⅣO and V~Ⅴ are calculated through use of the most recent stability constants; at biologically relevant concentrations (~1 μM, but definitely <10 μM) 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.
机译:对于了解人体血液中抗糖尿病钒络合物的生物转化以及钒如何转运至靶细胞的知识,了解人血清中钒的形态至关重要。可以通过两种完全不同的方法获取此类信息:分离技术和建模计算。本文主要针对后者。人血清中两种主要的金属离子结合剂是载铁蛋白(apoTf)和人血清白蛋白(HSA),并详细讨论了它们与V〜ⅣO和V〜Ⅴ的相互作用。引入了部分新的HSA-V〜ⅣO相互作用模型,其中两个结合位点(一个对两个和一个对一个金属离子)不仅相互竞争,而且还与金属离子的水解竞争。还着重研究了V〜ⅣO,血清蛋白和候选药物配体(麦芽酚(mal),1,2-二甲基-3-羟基-4(1H)-吡啶酮(dhp),乙酰丙酮(acac)和吡啶甲酸(pic)):对不同研究组报告的不同三元复合物的结构和形成常数进行了严格审查。 V〜ⅣO和V〜Ⅴ的血清形态是通过使用最新的稳定性常数计算得出的。在生物学相关浓度(〜1μM,但绝对小于10μM)下,apoTf络合物对两种金属离子均占主导地位。其结果是,直到钒被吸收到血清中为止,原始复合物的候选药物配体的主要作用是载体功能,并且钒离子本身是负责抗糖尿病作用的活性代谢物。

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