Iodination catalyzed by the xanthine oxidase system: role of hydroxyl radicals.
Iodination catalyzed by the xanthine oxidase system: role of hydroxyl radicals.
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黄嘌呤氧化酶系统催化的碘化：羟基自由基的作用。
DOI：
10.1021/bi00260a030
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发表时间：
1982
期刊：
影响因子：
2.9
通讯作者：
Klebanoff,SJ
中科院分区：
文献类型：
--
作者：
Klebanoff,SJ
Seymour J. Klebanoff摘要：描述了三种依赖于乙酰基脱黄嘌呤氧化酶（XO）系统的碘化系统。在一种情况下，最佳活性依赖于髓过氧化物酶（MPO）和氯化物的补充，过氧化氢酶而不是超氧化物歧化酶或OH-清除剂的抑制表明，黄嘌呤氧化酶系统产生的H2O2是必需的。过氧化物酶和H2O2对碘化的催化作用已得到充分证实，并且这种碘化作用可被氯化物刺激。第二个碘化体系需要Fe~（2+）和乙二胺四乙酸（EDTA）的络合才能获得最佳的碘化活性。碘化被过氧化氢酶、超氧化物歧化酶和OH-清除剂乙醇和甘露醇抑制，表明需要通过Fe2 +-EDTA催化的O2-和H2O2之间的相互作用（Haber-Weiss反应）产生OH-。Fe~（2+）-EDTA-补充系统对叠氮化物的抑制作用比MPO-氯化物系统的敏感性低得多，并且前者而不是后者系统被三（羟甲基）-氨基甲烷缓冲液抑制。这两个系统都有一个中性或碱性pH值的最佳值。第三XO依赖性碘化系统需要Fe 2+，但被EDTA抑制。碘化是最佳的醋酸盐缓冲液，pH 5.0 - 5.5，在浓度为0.02 M或更低，并抑制磷酸盐，乳酸盐和柠檬酸盐缓冲液。XO系统可以用H2O2代替。在Fe~（2+）-EDTA体系中，过氧化氢酶、乙醇、甘露醇和叠氮化物均能抑制碘化反应，而超氧化物歧化酶则不受抑制，除非Fe~（2+）浓度降低。提出了H_2O_2与Fe~（2+）（芬顿试剂）相互作用形成OH-的条件。所有三个系统对氰化物、甲巯咪唑和丙基硫氧嘧啶的抑制同样敏感。这些研究结果进行了讨论有关的OH-在生物碘化反应中可能发挥的作用。在许多生物系统中发生碘化物向有机物的转化（碘化）。通常与蛋白质中的酪氨酸残基形成共价键以形成单碘和二碘酪氨酸;然而，组氨酸和巯基以及某些其他低分子量化合物和脂质可以被碘化。蛋白质的碘化通常通过碘化物转化为三氯乙酸可沉淀形式来测量。过氧化物酶在补充H2O2和碘化物时是碘化反应的有效催化剂[综述参见莫里森& Schonbaum（1976）]。体内碘化的主要部位是甲状腺，甲状腺激素的合成是由甲状腺球蛋白中酪氨酸残基的碘化启动的;甲状腺过氧化物酶已被免疫。
Seymour J. Klebanoff abstract: Three iodinating systems dependent on the acetaldehyde-xanthine oxidase (XO) system are described. In one, optimal activity was dependent on supplementation with myeloperoxidase (MPO) and chloride, and inhibition by catalase but not superoxide dismutase or OH-scavengers suggested that H202generated by the xanthine oxidase system is required. The catalysis of iodination by peroxidase and H202 is well established, and this iodination can be stimulated by chloride. The second iodinating system required supplemen-tation by Fe2+ and ethylenediaminetetraacetic acid (EDTA) for optimal activity. Iodination was inhibited by catalase, superoxide dismutase, and the OH-scavengers ethanol and mannitol, suggesting a requirement for OH-generated by the Fe2+-EDTA-catalyzed interaction between 02-and H202 (Haber-Weiss reaction). The Fe2+-EDTA-supplemented system was considerably less sensitive to inhibition by azide than was the MPO-chloride system, and the former but not the latter system was inhibited by tris (hydroxymethyl)-aminomethane buffer. Both systems had a neutral or alkaline pH optimum. The third XO-dependent iodinating system required Fe2+ but was inhibited by EDTA. Iodination was optimal inacetate buffer, pH 5.0-5.5, at concentrations of 0.02 M or less and was inhibited by phosphate, lactate, and citrate buffers. The XO system could be replaced by H202. Iodination was inhibited bycatalase, ethanol, mannitol, and azide as in the Fe2+-EDTA-supplemented system; however, super-oxide dismutase was not inhibitory unless the Fe2+ concen-tration was lowered. A requirement for OH-formed by the interaction of H202 and Fe2+(Fenton’s reagent) was proposed. All three systems were equally sensitiveto inhibition by cyanide, methimazole, and propylthiouracil. These findings are discussed in relation to a possible role for OH-in biological iodination reactions. e conversion of iodide to organicform (iodination) occurs in a number of biological systems. A covalent bond is formed generally with tyrosine residues in protein to form mono-and diiodotyrosine; however, histidine and sulfhydryl groups and certain other low molecular weight compounds and lipids can be iodinated. The iodination of protein is generally measured by the conversion of iodide to a trichloroacetic acid precipitable form.Peroxidases, when supplemented with H202 and iodide, are potent catalysts of the iodination reaction [for review, see Morrison & Schonbaum (1976)]. The predominant site of iodination in the body is the thyroid gland where thyroid hormone synthesis is initiated by the iodination of tyrosine residues in thyroglobulin; a thyroid peroxidase has been im-