Ollinger K, Buffinton G D, Ernster L, Cadenas E
Department of Pathology II, University of Linköping, Sweden.
Chem Biol Interact. 1990;73(1):53-76. doi: 10.1016/0009-2797(90)90108-y.
The effect of superoxide dismutase on the autoxidation of hydro- and semi-1,4-naphthoquinones with different substitution pattern and covering a one-electron reduction potential range from -95 to -415 mV was examined. The naphthoquinone derivatives were reduced via one or two electrons by purified NADPH-cytochrome P-450 reductase or DT-diaphorase, respectively. Superoxide dismutase did not alter or slightly enhance the initial rates of enzymic reduction, whereas it affected in a different manner the following autoxidation of the semi- and hydroquinones formed. Autoxidation was assessed as NADPH oxidation in excess to the amounts required to reduce the quinone present, H2O2 formation, and the redox state of the quinones. Superoxide dismutase enhanced 2--8-fold the autoxidation of 1,4-naphthosemiquinones, following the reduction of the oxidized counterpart by NADPH-cytochrome P-450 reductase, except for the glutathionyl-substituted naphthosemiquinones, whose autoxidation was not affected by superoxide dismutase. Superoxide dismutase exerted two distinct effects on the autoxidation of naphthohydroquinones formed during DT-diaphorase catalysis: on the one hand, it enhanced slightly the autoxidation of 1,4-naphthohydroquinones with a hydroxyl substituent in the benzene ring: 5-hydroxy-1,4-naphthoquinone and the corresponding derivatives with methyl- and/or glutathionyl substituents at C2 and C3, respectively. On the other hand, superoxide dismutase inhibited the autoxidation of naphthohydroquinones that were either unsubstituted or with glutathionyl-, methyl-, methoxyl-, hydroxyl substituents (the latter in the quinoid ring). The inhibition of hydroquinone autoxidation was reflected as a decrease of NADPH oxidation, suppression of H2O2 production, and accumulation of the reduced form of the quinone. The enhancement of autoxidation of 1,4-naphthosemiquinones by superoxide dismutase has been previously rationalized in terms of the rapid removal of O2-. by the enzyme from the equilibrium of the autoxidation reaction (Q2-. + O2----Q + O2-.), thus displacing it towards the right. The superoxide dismutase-dependent inhibition of H2O2 formation as well as NADPH oxidation during the autoxidation of naphthohydroquinones--except those with a hydroxyl substituent in the benzene ring--seems to apply to those organic substrates which can break down with simultaneous formation of a semiquinone and O2-.. Inhibition of hydroquinone autoxidation by superoxide dismutase can be interpreted in terms of suppression by the enzyme of O2-.- dependent chain reactions or a direct catalytic interaction with the enzyme that might involve reduction of the semiquinone at expense of O2(-.).(ABSTRACT TRUNCATED AT 400 WORDS)
研究了超氧化物歧化酶对具有不同取代模式、一电子还原电位范围为-95至-415 mV的氢醌和半醌1,4-萘醌自氧化的影响。萘醌衍生物分别通过纯化的NADPH-细胞色素P-450还原酶或DT-黄递酶经一或两个电子还原。超氧化物歧化酶未改变或略微提高酶促还原的初始速率，而它以不同方式影响随后形成的半醌和氢醌的自氧化。自氧化通过相对于还原存在的醌所需量过量的NADPH氧化、H2O2形成以及醌的氧化还原状态来评估。在NADPH-细胞色素P-450还原酶将氧化型对应物还原后，超氧化物歧化酶使1,4-萘半醌的自氧化增强2至8倍，但谷胱甘肽取代的萘半醌除外，其自氧化不受超氧化物歧化酶影响。超氧化物歧化酶对DT-黄递酶催化过程中形成的萘氢醌的自氧化产生两种不同影响：一方面，它略微增强了苯环中带有羟基取代基的1,4-萘氢醌的自氧化：5-羟基-1,4-萘醌以及分别在C2和C3带有甲基和/或谷胱甘肽取代基的相应衍生物。另一方面，超氧化物歧化酶抑制未取代或带有谷胱甘肽、甲基、甲氧基、羟基取代基（后者在醌环中）的萘氢醌的自氧化。对氢醌自氧化的抑制表现为NADPH氧化减少、H2O2产生的抑制以及醌还原形式的积累。超氧化物歧化酶对1,4-萘半醌自氧化的增强作用先前已根据酶从自氧化反应平衡（Q2- + O2----Q + O2-）中快速去除O2-进行了合理说明，从而使其向右移动。超氧化物歧化酶对萘氢醌自氧化过程中H2O2形成以及NADPH氧化的抑制作用（苯环中带有羟基取代基的除外）似乎适用于那些可分解同时形成半醌和O2-的有机底物。超氧化物歧化酶对氢醌自氧化的抑制作用可通过酶对O2-依赖性链反应的抑制或与酶的直接催化相互作用来解释，这可能涉及以O2(-)为代价还原半醌。（摘要截断于400字）
