URIC-ACID IRON-ION COMPLEXES - A NEW ASPECT OF THE ANTIOXIDANT FUNCTIONS OF URIC-ACID
URIC-ACID IRON-ION COMPLEXES - A NEW ASPECT OF THE ANTIOXIDANT FUNCTIONS OF URIC-ACID
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DOI：
10.1042/bj2350747
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发表时间：
1986-05-01
影响因子：
4.1
通讯作者：
HOCHSTEIN, P
中科院分区：
文献类型：
--
作者：
DAVIES, KJA;SEVANIAN, A;HOCHSTEIN, P
为了在氧气环境中生存，好氧生物已经开发了许多机制来保护免受氧自由基和单线态氧的侵害。其中一种机制，似乎在灵长类进化过程中具有特殊意义，是尿酸对氧自由基、单线态氧、氧代血红素氧化剂和过氧化氢自由基的直接清除。在本文中，我们证明了尿酸的另一个重要的“抗氧化”特性是与铁离子形成稳定配位络合物的能力。尿酸盐-Fe 3+络合物的形成显著抑制Fe 3+催化的抗坏血酸氧化，以及脂质体和大鼠肝微粒体组分中的脂质过氧化。与抗氧化剂清除剂反应相反，尿酸盐结合铁离子的能力提供的抗坏血酸氧化和脂质过氧化的抑制不涉及尿酸盐氧化。用荧光猝灭法测定了尿酸盐-铁离子络合物的缔合常数。发现1 ∶ 1尿酸盐-Fe 3+络合物的Ka为2.4 × 10 - 6。105，而1 ∶ 1尿酸盐-Fe 2+络合物的Ka测定为1.9 × 105。104.我们的实验还表明，尿酸盐可以与Fe 3+形成2：1的络合物，第二个尿酸盐分子的缔合常数（K“a）约为1.5。4.5. times. 105.从这些数据中，我们估计了总体稳定性常数（Ks.卡时代。K 'a）对于约为0.0001的尿酸盐-Fe 3+络合物。1.1. times. 1011.极谱测量显示（结合后）尿酸盐将Fe 2 +/Fe 3+半反应的还原电位从-0.77 V降低至-0.67 V。因此，尿酸盐略微降低了Fe 3+的氧化电位。目前的结果提供了一个机械的解释，我们以前的报告，尿酸盐保护抗坏血酸从人体血液中的氧化。通常在人血浆中发现的尿酸盐的几乎饱和浓度（高达0.6mM）代表血浆抗坏血酸盐浓度的5-10倍，并且比“游离"铁离子浓度高几个数量级。这些考虑指出了我们发现的生理意义。
In order to survive in an oxygen environment, aerobic organisms have developed numerous mechanisms to protect against oxygen radicals and singlet oxygen. One such mechanism, which appears to have atained particular significance during primate evolution, is the direct scavenging of oxygen radicals, singlet oxygen, oxo-haem oxidants and hydroperoxyl radicals by uric acid. In the present paper we demonstrate that another importnat ''antioxidant'' property of uric acid is the ability to form stable co-ordination complexes with iron ions. Formation of urate-Fe3+ complexes dramatically inhibits Fe3+-catalysed ascorbate oxidation, as well as lipid peroxidation in liposomes and rat liver microsomal fraction. In contrst with antioxidant scavenger reactions, the inhibition of ascorbate oxidation and lipid peroxidation provided by urate''s ability to bind iron ions does not involve urate oxidation. Association constants (Ka) for urate-iron ion complexes were determined by fluorescence-quenching techniques. The Ka for a 1:1 urate-Fe3+ complex was found to be 2.4 .times. 105, whereas the Ka for a 1:1 urate-Fe2+ complex was determined to be 1.9 .times. 104. Our experiments also revealed that urate can form a 2:1 complex with Fe3+ with an association constant for the second urate molecule (K''a) of approx. 4.5 .times. 105. From these data we estimate an overall stability constant (Ks .simeq. Ka .times. K''a) for urate-Fe3+ complexes of approx. 1.1 .times. 1011. Polarographic measurements revealed that (upon binding) urate decreases the reduction potential for the Fe2+/Fe3+ half-reaction from -0.77 V to -0.67 V. Thus urate slightly diminishes the oxidizing potential of Fe3+. The present results provide a mechanistic explanation for our previous report that urate protects ascorbate from oxidation in human blood. The almost saturating concentration of urate normally found in human plasma (up to 0.6 mM) represents 5-10 times the plasma ascorbate concentration, and is orders of magnitude higher than the ''free'' iron ion concentration. These considerations point to the physiological significance of our findings.