ENZYMES IN ANIMAL METABOLISM OF OXALATE DERIVATIVES

这个实验室的几项研究最近 一致认为草酸的各种衍生物， 特别是草酰硫醇酯（RSCOCOO-），可能发挥重要作用， 在控制动物代谢中的作用，并可能作为 某些激素的调节剂，特别是胰岛素和生长 因素 如果是这样的话，那么似乎有必要充分 表征，参与的总体代谢途径 这些化合物的生物合成和催化，以及这些化合物的具体用途。 催化途径中各个步骤的酶。 的 这是拟议研究的总体目标。 一些具体 方法和酶，将在拟议的研究 研究包括：（1）一种膜结合的酰胺酶， 将酰基辅酶A衍生物分离为S-酰基半胱胺 并进行了表征，（2）各种S-酰基半胱胺的反应性 在胆碱酯酶的催化下， 研究，（3）探讨草酸衍生物是否 （噻唑啉-2-羧酸酯），这是怀疑的产物 由D-氨基酸氧化酶催化的生理反应， 酶促转化为草酰硫醇酯，（4）分离和 描述一种酶， （水解？）来自肾匀浆的N-草酰半胱氨酸，和 (5)探索草酰硫醇酯是否可能是 芳香族氨基酸和抗坏血酸（维生素C）的代谢 变成草酸盐。 这项研究可能会导致一个整体的阐明 新的动物代谢控制系统。 不仅可能 特别是与胰岛素相关的疾病，糖尿病， 也可用于癌症等疾病，因为各种生长因子和 癌基因的蛋白质产物似乎与胰岛素密切相关。 在 描述了动物中草酸盐的新代谢途径， 可能有助于我们理解 肾结石的症状 最后，如果草酰 发现衍生物是抗坏血酸催化剂的中间体， 它将大大阐明这种维生素在 预防坏血病等疾病。

Several lines of research in this laboratory have recently converged to suggest that various derivatives of oxalic acid, especially oxalyl thiolesters (RSCOCOO-), may play an important role in controlling metabolism in animals, and may function as mediators for some hormones, especially insulin and growth factors. If this is the case, then it seems imperative to fully characterize, both the overall metabolic pathways involved in the biosynthesis and catabolism of such compounds, and the specific enzymes that catalyze the individual steps in the pathways. That is the general goal of the proposed research. Some specific approaches and enzymes that will be investigated in the proposed research include: (1) a membrane bound amidase that cleaves S- acyl coenzyme A derivatives to S-acylcysteamines will be isolated and characterized, (2) the reactivity of various S-acylcysteamines toward hydrolysis, catalyzed by cholinesterases will be investigated, (3) explore whether the oxalate derivative (thiazoline-2-carboxylate), that is the product of the suspected physiological reaction catalyzed by D-amino acid oxidase, is enzymically converted into oxalyl thiolesters, (4) isolate and characterize an enzyme that causes the disappearance (hydrolysis?) of N-oxalylcysteine from kidney homogenates, and (5) explore whether oxalyl thiolesters may be intermediates in the metabolism of aromatic amino acids and ascorbic acid (vitamin C) to oxalate. The research potentially could lead to the elucidation of a whole new system of metabolic control in animals. Not only may it be particularly relevant to the insulin related disease, diabetes, but also to diseases such as cancer, since various growth factors and protein products of oncogenes seem closely related to insulin. In characterizing new metabolic pathways to oxalate in animals, it may aid in our understanding of the reasons for the development of kidney stones due to calcium oxalate. Finally, if oxalyl derivatives are found to be intermediates in ascorbate catabolism, it will clarify considerably the role of this vitamin in the prevention of diseases such as scurvy.