Pezzella A, d'Ischia M, Napolitano A, Misuraca G, Prota G
Department of Organic and Biological Chemistry, University of Naples Federico II, Italy.
J Med Chem. 1997 Jul 4;40(14):2211-6. doi: 10.1021/jm970099t.
Exposure of dopamine to an excess of linoleic acid 13-hydroperoxide (13-hydroperoxyoctadecadienoic acid) in the presence of ferrous ions in Tris buffer, pH 7.4, resulted in a relatively fast, oxygen-independent reaction exhibiting first-order kinetics with respect to both catecholamine and metal concentrations. Product analysis in the early stages revealed the presence of significant amounts of the quinone of the neurotoxin 6-hydroxydopamine, together with some aminochrome and ill-defined melanin-like material. Quinone formation required the presence of iron, either in the ferrous or ferric form, and was unaffected by peroxidase, catalase, and hydroxyl radical scavengers, e.g. mannitol, as well as biologically relevant antioxidants, like ascorbate and glutathione. Hydrogen peroxide proved as effective as linoleic acid hydroperoxide in inducing dopamine oxidation and conversion to 6-hydroxydopamine quinone. Metal chelators, including EDTA and bipyridyl, markedly suppressed quinone formation without, however, inhibiting dopamine oxidation. These and other results are consistent with a hydroxyl radical independent hydroxylation/oxidation mechanism basically different from the Fenton reaction, which involves direct interaction of the peroxide with a dopamine-Fe(III) chelate generated during the process.
在pH 7.4的Tris缓冲液中，多巴胺在亚铁离子存在的情况下与过量的亚油酸13 - 氢过氧化物（13 - 氢过氧化十八碳二烯酸）接触，导致了一个相对快速的、不依赖氧气的反应，该反应对儿茶酚胺和金属浓度均呈现一级动力学。早期阶段的产物分析表明，存在大量神经毒素6 - 羟基多巴胺的醌，以及一些氨基色素和不明确的黑色素样物质。醌的形成需要亚铁或铁形式的铁存在，并且不受过氧化物酶、过氧化氢酶和羟基自由基清除剂（如甘露醇）以及生物相关抗氧化剂（如抗坏血酸和谷胱甘肽）的影响。过氧化氢在诱导多巴胺氧化并转化为6 - 羟基多巴胺醌方面与亚油酸氢过氧化物一样有效。包括EDTA和联吡啶在内的金属螯合剂显著抑制醌的形成，但不抑制多巴胺氧化。这些以及其他结果与一种不依赖羟基自由基的羟基化/氧化机制一致，该机制与芬顿反应基本不同，芬顿反应涉及过氧化物与过程中生成的多巴胺 - Fe(III)螯合物的直接相互作用。
