A MECHANISTIC STUDY OF SOME O2 OXIDOREDUCTASES

这项研究的长期目标是详细确定不同的 O2氧化还原酶催化O2的反应。因为这些酶是 许多代谢途径所必需的，包括：儿茶酚胺 生物合成和降解、芳香氨基酸代谢、肌醇 分解代谢、类固醇激素生物合成、药物代谢等，感觉到 更详细地了解它们的机制可能会导致 控制或减轻许多新陈代谢缺陷。三种特殊的酶 在即将到来的授权期将研究的是：肌醇加氧酶。 这种肾脏酶，它负责第一步在 肌醇的分解代谢，已知在患有 糖尿病，以酶复合体的形式存在于猪的肾脏中，含有 还有D-葡萄糖醛酸还原酶。建议用齐次的 猪肾酶将被特别设计来识别 反应，以及与酶复合体的研究将会受到关注 测定该络合物的物理和动力学特性，以及 通过探索加氧酶和还原酶的可能偶联 活动。二胺氧化酶。这种酶负责 几种生理上重要的二胺的代谢，包括 腐胺、组胺和半胱胺。一组实验，包括 均相猪肾酶旨在鉴定紧密结合的 这种酶含有的有机辅因子，另一个在探索 酶结合铜，三分之一在表征催化的氧化酶 半胱胺的反应。4-羟基苯基丙酮酸双加氧酶。这种酶， 它参与所有动物的酪氨酸代谢，是 与几种代谢性疾病有关。建议进行的实验 均一种猪肝酶的目的是识别可能的 反应中的中间体。

The long term goal of this research is to determine in detail how various O2 oxidoreductases catalyze reactions of O2. Since these enzymes are necessary for so many metabolic pathways, including: catecholamine biosynthesis and degradation, aromatic amino acid metabolism, inositol catabolism, steroid hormone biosynthesis, drug metabolism, etc, it is felt that a more detailed understanding of their mechanisms could lead to the control or alleviation of many metabolic defects. Three specific enzymes that will be studied in the coming grant period are: Inositol Oxygenase. This kidney enzyme, which is responsible for the first step in the catabolism of inositol, and which is known to be deficient in animals with diabetes mellitus, exists in hog kidney as an enzyme complex containing also D-glucuronate reductase. Proposed experiments with the homogeneous hog kidney enzyme will be specially designed to identify intermediates in the reaction, and studies with the enzyme complex will be concerned with determining the physical and kinetic characteristics of the complex, and with exploring the possible coupling of the oxygenase and reductase activities. Diamine Oxidase. This enzyme is responsible for the metabolism of several physiologically important diamines, including putrescine, histamine, and cystamine. One set of experiments with the homogeneous hog kidney enzyme is aimed at identifying the tightly bound organic cofactor this enzyme contains, another at exploring the role of the enzyme bound copper, and a third at characterizing the oxidase catalyzed reactions of cystamine. 4-Hydroxphenylpyruvate dioxygenase. This enzyme, which participates in the metabolism of tyrosine in all animals, is involved in several metabolic diseases. Proposed experiments with the homogeneous hog liver enzyme are aimed at identifying possible intermediates in the reaction.