Dykens J A, Sullivan S G, Stern A
Biochem Pharmacol. 1987 Jan 15;36(2):211-7. doi: 10.1016/0006-2952(87)90691-5.
The oxidative reactivities of four tryptophan metabolites in the kynurenine pathway were examined as a potential mechanism for their reported neurotoxicities and carcinogenicities. Neither quinolinic acid, a neurotoxin, nor its monocarboxylic analogue, picolinic acid, auto-oxidized over a wide pH range. However, 3-hydroxyanthranilic acid (3-HAT), a carcinogen, readily auto-oxidized and the reaction rate increased exponentially with increasing pH. 3-HAT auto-oxidation likely involves two steps: auto-oxidation of 3-HAT to the semiquinoneimine (anthranilyl radical) which oxidizes to the quinoneimine, followed by condensation and oxidation reactions to yield a second carcinogen, cinnabarinic acid. 3-HAT auto-oxidation to cinnabarinate required molecular oxygen and generated superoxide radicals and H2O2. Superoxide dismutase (SOD) accelerated 3-HAT auto-oxidation 4-fold, probably by preventing back reactions between superoxide and either the anthranilyl radical or the quinoneimine formed during the initial step of auto-oxidation. Catalase did not accelerate 3-HAT auto-oxidation, but it did prevent destruction of cinnabarinate by H2O2. Interconversion between oxyhemoglobin and methemoglobin occurred during 3-HAT auto-oxidation, although neither form of hemoglobin altered rates of 3-HAT auto-oxidation. Mn2+, Mn3+ and Fe3+-EDTA did not directly catalyze cinnabarinate formation in the absence of O2, but they did accelerate cinnabarinate formation under aerobic conditions.
对犬尿氨酸途径中四种色氨酸代谢物的氧化反应活性进行了研究，作为其已报道的神经毒性和致癌性的一种潜在机制。神经毒素喹啉酸及其单羧酸类似物吡啶甲酸在很宽的pH范围内都不会自动氧化。然而，致癌物3-羟基邻氨基苯甲酸（3-HAT）很容易自动氧化，并且反应速率随着pH值的增加呈指数增长。3-HAT自动氧化可能涉及两个步骤：3-HAT自动氧化为半醌亚胺（邻氨基苯甲酰基自由基），然后氧化为醌亚胺，接着进行缩合和氧化反应生成第二种致癌物朱砂酸。3-HAT自动氧化为朱砂酸盐需要分子氧，并产生超氧自由基和过氧化氢。超氧化物歧化酶（SOD）使3-HAT自动氧化加速了4倍，可能是通过防止超氧与自动氧化初始步骤中形成的邻氨基苯甲酰基自由基或醌亚胺之间的逆反应。过氧化氢酶没有加速3-HAT自动氧化，但它确实防止了过氧化氢对朱砂酸盐的破坏。在3-HAT自动氧化过程中发生了氧合血红蛋白和高铁血红蛋白之间的相互转化，尽管两种形式的血红蛋白都没有改变3-HAT自动氧化的速率。在没有氧气的情况下，Mn2+、Mn3+和Fe3+-EDTA不会直接催化朱砂酸盐的形成，但在有氧条件下它们确实加速了朱砂酸盐的形成。
