KINETICS AND MECHANISM OF IRON(III) REMOVAL FROM CITRATE BY DESFERRIOXAMINE-B AND 3-HYDROXY-1,2-DIMETHYL-4-PYRIDONE
KINETICS AND MECHANISM OF IRON(III) REMOVAL FROM CITRATE BY DESFERRIOXAMINE-B AND 3-HYDROXY-1,2-DIMETHYL-4-PYRIDONE
复制标题
DOI：
10.1021/ja00088a022
复制
发表时间：
1994-05-04
影响因子：
15
通讯作者：
NICK, H
中科院分区：
文献类型：
--
作者：
FALLER, B;NICK, H
测定了螯合剂去铁胺B（DFO）和3-羟基-1，2-二甲基-4-吡啶酮（L1）从柠檬酸盐中去除铁的二级速率常数。在pH 7.4和37 ℃下，Fe从柠檬酸盐转移到螯合剂的总速率常数k（on）对于DFO为4 M（-1）s（-1），对于L1为43 M（-1）s（-1）。铁从柠檬酸盐转移到两个螯合剂的动力学进行了详细研究，并提出了一个可能的机制。在金属离子转移之前，DFO和L1都与柠檬酸盐-铁形成混合络合物。该初始复合物的解离平衡常数对于DFO和L1分别为10和0.45 mM。DFO和L1解离成游离柠檬酸盐和螯合剂-Fe的一级速率常数分别为0.04和0.02 s（-1）。这些结果表明，在接近于螯合治疗期间体内达到的浓度（10-100 μ M）下，尽管DFO具有优于L1的热力学优势，但后者在动员柠檬酸盐结合铁方面的作用比DFO快10倍。铁去除动力学的这种大的差异主要是由于螯合剂和Fe-柠檬酸盐之间的初始络合物的平衡解离常数的差异。螯合剂与结合到其生物载体的铁形成暂时复合物的能力似乎是转移动力学的主要决定因素。我们的数据表明，通过DFO和L1从柠檬酸盐中去除Fe的反应途径与用转铁蛋白观察到的不同。与转铁蛋白不同，L1（以及在较小程度上DFO）能够直接与聚合柠檬酸铁相互作用;因此，柠檬酸铁的解聚不是转移动力学中的限速步骤。
The second-order rate constants for iron removal from citrate by the chelating agents desferrioxamine B (DFO) and 3-hydroxy-1,2-dimethyl-4-pyridone (L1) were determined. The overall rate constant k(on) for the transfer of Fe from citrate to the chelator is 4 M(-1) s(-1) for DFO and 43 M(-1) s(-1) for L1 at pH 7.4 and 37 degrees C. The kinetics of transfer of iron from citrate to the two chelators was examined in detail, and a possible mechanism is proposed. Both DFO and L1 form a mixed complex with citrate-iron prior to the transfer of the metal ion. The dissociation equilibrium constant of this initial complex is 10 and 0.45 mM for DFO and L1, respectively. The first-order rate constant for its dissociation into free citrate and chelator-Fe is 0.04 and 0.02 s(-1) for DFO and L1, respectively. These results indicate that, at concentrations close to what is achieved in vivo during chelation therapy (10-100 mu M), although DFO has a thermodynamic advantage over L1, the latter acts 10 times faster than DFO in mobilizing citrate-bound iron. This large difference in the kinetics of iron removal is mainly due to the difference in the equilibrium dissociation constant of the initial complex between the chelator and Fe-citrate. The ability of a chelating agent to make a transitory complex with the iron bound to its biological carrier seems to be a major determinant in the kinetics of transfer. Our data show that the reaction pathway for the removal of Fe from citrate by DFO and L1 is different from what was observed with transferrin. Unlike transferrin, L1 (and to a lesser extent DFO) is able to directly interact with the polymeric iron-citrate; thus, depolymerization of Fe-citrate is not the rate-limiting step in the kinetics of transfer.