VOLATILE ACID FORMATION IN PARASITIC HELMINTHS

许多寄生蠕虫肌肉线粒体的能量代谢 厌氧，与寄主有很大的不同。不饱和 有机酸被用作末端电子受体，而不是氧， 而能源生产与NADH依赖的减排相结合 富马酸和独特的Enoyl COAS。目前的提案旨在 描述有机酸代谢的几个不同方面 寄生线虫，猪蛔虫。这一主题不仅对 它提供了对这些“厌氧性”细胞功能的洞察力 细胞器，也是因为这些途径影响了其他一些小说 生化过程，其中许多过程也是 化疗。具体的研究将包括继续描述 参与厌氧能量产生的新型酶，如 丙酮酸脱氢酶复合体与2-甲基支链烯醇辅酶A 还原酶。这些酶似乎经过特殊的修饰才能发挥作用 在宿主肠道中存在的还原条件下，结果是 也是研究有氧运动中相应酶的极佳模型 线粒体。更重要的是，对纯化酶的洞察将是 扩展到对细菌厌氧电子传递调节的研究 亚线粒体颗粒和完整的线粒体，有机酸 肌肉外组织中的代谢，如皮下组织，以及 蛔虫幼虫发育过程中的有氧/无氧转变。这些研究 应识别有氧和无氧之间的功能差异 线粒体的长期目标是确定有机酸的作用 完整蠕虫的代谢与线粒体的调节 幼虫发育过程中的生物发生。

Energy metabolism in muscle mitochondria of many parasitic helminths is anaerobic and differs profoundly from that of the host. Unsaturated organic acids are used as terminal electron-acceptors, instead of oxygen, and energy-generation is coupled to the NADH-dependent reductions of fumarate and unique enoyl CoAs. The current proposal is designed to characterize a number of different aspects of organic acid metabolism in the parasitic nematode, Ascaris suum. This topic is important not only for the insight it provides into the functioning of these "anaerobic" organelles, but also because these pathways impact a number of other novel biochemical processes, many of which are also potential targets for chemotherapy. Specific studies will involve the continued characterization of novel enzymes involved in anaerobic energy-generation, such as the pyruvate dehydrogenase complex and the 2-methyl branched-chain enoyl CoA reductase. These enzymes appear to be specifically modified to function under the reducing conditions present in the host gut and turn out to be also excellent models for study of the corresponding enzymes from aerobic mitochondria. More importantly, insights on the purified enzymes will be expanded to studies of the regulation of anaerobic electron-transport in submitochondrial particles and intact mitochondria, organic acid metabolism in extramuscular tissues, such as hypodermis, and aerobic/anaerobic transitions in developing ascarid larvae. These studies should identify functional differences between aerobic and anaerobic mitochondria with the long term goal of defining the role of organic acid metabolism in the intact helminth and the regulation of mitochondrial biogenesis during larval development.