VOLATILE ACID FORMATION IN PARASITIC HELMINTHS

许多有效的驱虫药也抑制肌肉收缩。 通过直接干扰神经肌肉的过程 连接或抑制能量代谢的。自.以来 许多寄生蠕虫的线粒体代谢是 以厌氧为主，与 宿主，它是化疗攻击的潜在部位。 在之前的赠款期间，一些重要的见解 对参与线粒体的酶的调节 猪蛔虫寄生线虫的新陈代谢 描述。本研究旨在扩展这些研究。 并将重点放在已确定的 寄主和寄生虫。具体地说，一个新的组件 蛔虫丙酮酸脱氢酶复合体(PDC)将进一步 E_2乙酰化的性质、作用及其在细胞周期中的作用 PDC活性受其相关蛋白和蛋白的调节 磷酸酶将被鉴定。此外，监管还包括 NADH依赖的2-甲基支链烯醇CoA还原将 用亚线粒体颗粒进行表征并提纯 蛔虫酶、质子梯度和ADP的产生 直接测得磷酸化程度。由于Ca++似乎扮演着一个 蛔虫线粒体调控中的独特作用 在分离的蛔虫线粒体中的代谢，钙离子通量将 测量并与最终产品形成和能量相关- 一代。初步实验表明， 线粒体体积是有机酸的重要调节因子 在这些孤立的线粒体中形成，因此它的作用也 将会被描述。这些研究将允许开发 特性良好的蛔虫线粒体制剂，能够 在生理水平上的挥发性有机酸合成，以及 应提供更清晰的能源生产图景 这些细胞器经常被研究，但仍然知之甚少。 因为这些线粒体经常被用来筛选化合物 潜在的驱虫活性，清楚地了解它们的 函数对于有意义地截取结果是必不可少的， 尤其是因为它们与相应的 哺乳动物的细胞器。

Many effective anthelminthics inhibit muscle contraction, either by directly interfering with processes at the neuromuscular junction or inhibiting energy metabolism. Since the mitochondrial metabolism of many parasitic helminths is predominantly anaerobic and differs substantially from that of the host, it is a potential site for chemotherapeutic attack. During the previous grant period, a number of important insights into the regulation of the enzymes involved in the mitochondrial metabolism of the parasitic nematode, Ascaris suum, have been described. The present study is designed to extend these studies and concentrate on differences that have been identified between host and parasite. Specifically, a novel component of the ascarid pyruvate dehydrogenase complex (PDC) will be further characterized and its role and that of E2 acetylation in the regulation of PDC activity by its associated kinase and phosphatase will be identified. In addition, the regulation of NADH-dependent 2-methyl branched-chain enoyl CoA reduction will be characterized using submitochondrial particles and purified ascarid enzymes, and the generation of a proton-gradient and ADP phosphorylation measured directly. Since Ca++ appears to play a unique role in the regulation of ascarid mitochondrial metabolism, Ca++ fluxes in isolated ascarid mitochondria will be measured and correlated with end-product formation and energy- generation. Preliminary experiments have suggested that mitochondrial volume is an important regulator of organic acid formation in these isolated mitochondria so that its role also will be described. These studies will permit the development of well characterized preparations of ascarid mitochondria, capable of volatile organic acid synthesis at physiological levels, and should provide a much clearer picture of energy-generation in these often studied, but still poorly understood organelles. Since these mitochondria are often used to screen compounds for potential anthelminthic activity, a clear understanding of their function is essential to intercept results meaningfully, especially since they differ so profoundly from the corresponding mammalian organelles.