ENZYMES IN ANIMAL METABOLISM OF OXALATE DERIVATIVES

草酸盐衍生物动物代谢中的酶

• 批准号: 3238055
• 负责人: GORDON A HAMILTON
• 金额: $ 12.39万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3238055
• 关键词: acyl group; amidohydrolases; aminoacid metabolism; aminoacid oxidase; ascorbate; cholinesterases; cyclic aminoacid; cysteamine; cysteine; enzyme mechanism; enzyme substrate; guinea pigs; high performance liquid chromatography; hydrolase; laboratory rat; oxalates; thin layer chromatography; thioester; vitamin metabolism

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.

这个实验室的几个研究方向最近 汇聚到一起表明草酸的各种衍生物， 尤其是草酰硫酸酯(RSCOCOO-)，可能起到重要的作用 在控制动物新陈代谢中的作用，并可能作为 某些激素的中介物，特别是胰岛素和生长 各种因素。如果是这样的话，那么完全 表征，这两个整体代谢途径参与了 这类化合物的生物合成和分解代谢及其特异性 催化这些途径中的各个步骤的酶。那 是拟议研究的总体目标。一些特定的 建议中将研究的方法和酶 研究内容包括：(1)裂解S的膜结合酶-- 将分离S-酰基半胱胺的酰基辅酶A衍生物 和表征，(2)各种S-酰基半胱胺的反应性 对于由胆碱酯酶催化的水解， 调查，(3)探索草酸盐衍生物 (噻唑啉-2-羧酸盐)，即可疑产品 D-氨基酸氧化酶催化的生理反应 酶法转化为草酰硫酸酯，(4)分离和 描述一种导致消失的酶的特征 (水解法？)从肾匀浆中提取N-草酰半胱氨酸，以及 (5)探索草酰基硫酸酯是否可能是 芳香氨基酸和抗坏血酸(维生素C)的代谢 草酸。 这项研究可能会导致对整个 动物代谢控制的新系统。它不仅可能是 尤其与胰岛素相关的疾病，糖尿病，但 也适用于癌症等疾病，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……里面 描述了动物体内草酸的新代谢途径，它 可能有助于我们了解发展的原因 草酸钙导致的肾结石。最后，如果草甘膦 研究发现，衍生物是抗坏血酸分解代谢的中间产物， 它将在很大程度上阐明这种维生素在 防止坏疽等疾病的发生。