VOLATILE ACID FORMATION IN PARASITIC HELMINTHS

许多寄生蠕虫肌肉线粒体的能量代谢是 它是厌氧的，与宿主的差异很大。不饱和 使用有机酸作为末端电子受体，代替氧， 而能量的产生与依赖于NADH的 富马酸和独特的烯酰辅酶A。目前的建议旨在 表征有机酸代谢的许多不同方面， 寄生线虫猪蛔虫这个问题不仅对 它提供了深入了解这些“厌氧”的功能， 细胞器，但也因为这些途径影响了一些其他新的 生物化学过程，其中许多也是潜在的目标， 化疗具体的研究将涉及继续表征 参与厌氧能量产生的新型酶，如 丙酮酸脱氢酶复合物和2-甲基支链烯酰辅酶A 还原酶。这些酶似乎经过特殊修饰， 在宿主肠道中存在的还原条件下， 也是研究有氧代谢中相应酶的优良模型 线粒体更重要的是，对纯化酶的了解将是 扩大到研究厌氧电子传递的调节， 亚线粒体颗粒和完整线粒体，有机酸 在肌外组织如皮下组织中的代谢，和 发育中蛔虫幼虫的需氧/厌氧转变。这些研究 应确定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 完整蠕虫的代谢和线粒体的调节 幼虫发育期间的生物发生。

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.