INTERACTIONS BETWEEN METALS, LIGANDS, AND OXYGEN IN THE AUTOXIDATION OF 6-HYDROXYDOPAMINE - MECHANISMS BY WHICH METAL CHELATION ENHANCES INHIBITION BY SUPEROXIDE-DISMUTASE
INTERACTIONS BETWEEN METALS, LIGANDS, AND OXYGEN IN THE AUTOXIDATION OF 6-HYDROXYDOPAMINE - MECHANISMS BY WHICH METAL CHELATION ENHANCES INHIBITION BY SUPEROXIDE-DISMUTASE
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DOI：
10.1016/0003-9861(87)90497-8
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发表时间：
1987-12-01
影响因子：
3.9
通讯作者：
DAVISON, AJ
中科院分区：
文献类型：
--
作者：
BANDY, B;DAVISON, AJ
过渡金属离子和超氧化物在不同程度上参与不同的自氧化。在pH7.0或8.0的6-羟基多巴胺（6-OHDA）与氧的反应中，加入5 ~ 300 U/ml的超氧化物歧化酶，在最高浓度下可抑制96%的自氧化。超氧化物歧化酶在5-20 U/ml浓度下单独存在时抑制小于40%，但在去铁胺或组氨酸存在下抑制超过99%。EDTA也增强了20 U/ml的超氧化物歧化酶的抑制86%，即使EDTA加速6-OHDA的自氧化时，单独存在或与去铁胺。与此相反，其他配体，如ADP或植酸，有很少或没有影响展览超氧化物歧化酶。蛋白质，如白蛋白，细胞色素氧化酶，或变性超氧化物歧化酶也增强抑制活性超氧化物歧化酶从不到40%到超过90%。显然，在氧化还原活性金属的存在下，通过内球电子转移发生自氧化，推测在三元6-OHDA内。金属. cntdot.氧络合物该机制不涉及游离O2-，也不受超氧化物歧化酶的抑制。另一方面，某些配体（包括蛋白质）的存在降低了痕量金属通过内球机制与6-OHDA或氧交换电子的能力。这些配体使自氧化依赖于O2-的繁殖，因此可被超氧化物歧化酶抑制。以前相互矛盾的报道，超氧化物歧化酶单独表现出6-OHDA自氧化，因此可以解释的基础上，在足够的浓度的脱辅基蛋白协调微量金属，以这种方式排除内球金属催化。
Transition metal ions and superoxide participate in different autoxidations to a variable extent. In the reaction of 6-hydroxydopamine (6-OHDA) with oxygen at pH 7.0 or 8.0, addition of 5 to 300 U/ml superoxide dismutase inhibited autoxidation by up to 96% at the highest concentrations. Superoxide dismutase at concentrations of 5-20 U/ml inhibited by less than 40% when present alone, but inhibited by over 99% in the presence of desferrioxamine or histidine. EDTA also enhanced the inhibition by 20 U/ml superoxide dismutase to 86%, even though EDTA accelerated the autoxidation by 6-OHDA when present alone or with desferrioxamine. In contrast, other ligands, such as ADP or phytic acid, had little or no effect on exhibition by superoxide dismutase. Proteins such as albumin, cytochrome oxidase, or denatured superoxide dismutase also enhanced inhibition by active superoxide dismutase from less than 40% to over 90%. Evidently, in the presence of redox active metals, autoxidation occurs by inner sphere electron transfer, presumably within a ternary 6-OHDA .cntdot. metal .cntdot. oxygen complex. This mechanism does not involve free O2- and not inhibited by superoxide dismutase. On the other hand, the presence of certain ligands (including proteins) diminishes the ability of trace metals to exchange electrons with 6-OHDA or oxygen by an inner sphere mechanism. These ligands render autoxidation dependent on propagation by O2- and therefore inhibitable by superoxide dismutase. Previously conflicting reports that superoxide dismutase alone exhibits 6-OHDA autoxidation are thus explicable on the basis that at sufficient concentration the apoprotein coordinates trace metals in such way to preclude inner sphere metal catalysis.