INTERMEDIATES IN THE AEROBIC AUTOXIDATION OF 6-HYDROXYDOPAMINE - RELATIVE IMPORTANCE UNDER DIFFERENT REACTION CONDITIONS
INTERMEDIATES IN THE AEROBIC AUTOXIDATION OF 6-HYDROXYDOPAMINE - RELATIVE IMPORTANCE UNDER DIFFERENT REACTION CONDITIONS
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DOI：
10.1016/0891-5849(89)90054-3
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发表时间：
1989-01-01
影响因子：
7.4
通讯作者：
DAVISON, AJ
中科院分区：
文献类型：
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作者：
GEE, P;DAVISON, AJ
6-羟基多巴胺(6-OHDA)的自氧化通过一个平衡的网络进行：过渡金属离子、超氧化物、过氧化氢、羟基自由基和其他物种。每种清除剂对反应机理的贡献都有很大不同，这取决于存在哪些清除剂。当其他传播媒介的参与减少时，每个传播媒介的贡献就会增加。因此，当过渡金属离子结合时(特别是在较高的pH下)，超氧化物(当金属离子可以参与时相对不重要)主导反应，在过氧化氢酶和螯合剂的同时存在时，它变得必不可少。如果排除超氧化物，过渡金属离子参与更多；如果同时排除cntdot.O2-和金属离子，过氧化氢变得更重要；如果同时排除H2O2和.cntdot.O2-，羟基自由基对反应机理贡献更大。超氧化物歧化酶被两种不同的机制强烈抑制：一种是高亲和力机制(在催化有效浓度下抑制13%)，另一种是低亲和力机制(在最高浓度下几乎完全抑制)，它依赖于金属结合和催化作用。在DETAPAC存在下，催化浓度对超氧化物歧化酶的抑制率达98%以上。相反，在超氧化物歧化酶存在的情况下，金属螯合剂具有强烈的抑制作用。当单独存在时，它们刺激(如EDTA)、抑制(如去铁胺)或几乎没有作用(如DETAPAC)。单独加入时，过氧化氢酶有轻微但稳定的刺激作用(5%)，在超氧化物歧化酶+DETAPAC存在下抑制100%。然而，在没有DETAPAC的情况下，过氧化氢酶降低了超氧化物歧化酶的抑制作用，反应速度提高了100%。羟基清除剂(甲酸盐、甘露醇或葡萄糖)单独产生的抑制很少或没有(10%)，但在过氧化氢酶+超氧化物歧化酶存在的情况下抑制30%。矛盾的是，他们在过氧化氢酶+超氧化物歧化酶+DETAPAC存在的情况下刺激了反应。
Autoxidation of 6-hydroxydopamine (6-OHDA) proceeds through a blanced network of: transition metal ions, superoxide, hydrogen peroxide, hydroxyl radicals, and other species. The contribution of each to the reaction mechanism varies dramatically depending upon which scavengers are present. The contribution of each propagating intermediate increases when the involvement of others is diminished. Thus, superoxide (which is relatively unimportant when metal ions can participate) dominates the reaction when transition metal ions are bound (especially at higher pH), and it becomes essential in the simultaneous presence of catalase plus chelators. Transition metal ions participate more if superoxide is excluded; hydrogen peroxide becomes more important if both .cntdot.O2- and metal ions are excluded; and hydroxyl radicals contribute more to the reaction mechanism if both H2O2 and .cntdot.O2- are excluded. Superoxide dismutase inhibited strongly, by two distinct mechanisms: a high affinity mechanism (< 13% inhibition) at catalytically effective concentrations, and a low affinity mechanism (almost complete inhibition at the highest concentrations) which depends upon both metal binding and catalytic actions. In the presence of DETAPAC catalytic concentrations of superoxide dismutase inhibited by over 98%. Conversely, metal chelating agents inhibited strongly in the presence of superoxide dismutase. When present alone they stimulated (like EDTA), inhibited (like desferrioxamine), or had little effect (like DETAPAC). Catalase which stimulated slightly but consistently (< 5%) when added alone, inhibited 100% in the presence of superoxide dismutase + DETAPAC. However, in the absence of DETAPAC, catalase decreased inhibition by superoxide dismutase, yielding a 100% increase in reaction rate. Hydroxyl scavengers (formate, mannitol or glucose) alone produced little or no (< 10%) inhibition, but inhibited by 30% in the presence of catalase + superoxide dismutase. Paradoxically, they stimulated the reaction in the presence of catalase + superoxide dismutase + DETAPAC.