VOLATILE ACID FORMATION IN PARASITIC HELMINTHS

寄生线虫造成了严重的医学和兽医问题，但是控制这些感染的化疗是有限的。大多数驱虫药抑制咽泵/肌肉收缩；因此，本研究旨在继续表征寄生线虫Ascaris suum中存在的新型厌氧线粒体：丙酮酸脱氢酶复合物（PDC）在调节这些厌氧线粒体途径中起关键作用，其调节和亚基组成在发育过程中发生巨大变化。将从需氧幼虫阶段纯化PDC，并将其调控和亚基组成与成虫PDC进行比较，以表征这些转变过程中的关键变化。不同亚基特异性同种异构体的规则将被检查，使用亚基分辨率和杂交复合物的重组。最后，在分离的线粒体制剂中，调节PDC活性状态和最终产物形成的因素将被直接检查。与脊椎动物肌肉不同的是，ca++似乎并不是成年南须鲸肌肉收缩与能量产生增加之间的重要信号。相反，似乎肌肉收缩和能量产生都可能受到多种生理配体的潜在调节，包括血清素和fmrfamilide样神经肽，它们通过多种第二信使系统起作用。因此，肌肉张力和咽泵将在体外系统中测量，并将与第二信使水平、葡萄糖/糖原利用、关键酶的活性状态和最终产物形成的配体依赖性变化相关。这些实验应该为咽泵和肌肉收缩的激素调节提供丰富的关键基线数据，这是驱虫虫发育和肌肉代谢的两个关键领域，以及收缩和代谢如何联系的关键见解。

Parasitic nematodes pose significant medical and veterinary problems, but chemotherapy to control many of these infections is limited. Most anthelminthics inhibit pharyngeal pumping/muscle contraction; therefore, the present study was designed to continue the characterization of the novel anaerobic mitochondria present in the parasitic nematode, Ascaris suum: The pyruvate dehydrogenase complex (PDC) plays a key role in regulating these anaerobic mitochondrial pathways and its regulation and subunit composition change dramatically during development. The PDC will be purified from aerobic larval stages and their regulation and subunit compositions compared to that of the adult PDC to characterize key modifications during these transitions. The regulations of the different subunit specific isoforms will be examined, using subunit resolution and the reconstitution of hybrid complexes. Finally, factors regulating the activity state of the PDC and end-product formation in isolated mitochondrial preparations will be examined directly. Ca++ does not appear to be an important signal linking muscle contraction with increased energy-generation in adult A. suum, as it does in vertebrate muscle. Instead, it appears that muscle contraction and energy-generation may both be potentially regulated by a variety of physiological ligands, including serotonin and FMRFamide-like neuropeptides, acting through a variety of second messenger systems. Therefore, muscle tension and pharyngeal pumping will be measured in vitro systems and will be correlated with ligand-dependent changes in second messenger levels, glucose/glycogen utilization, the activity states of key enzymes and end- product formation. These experiments should provide a wealth of critical base-line data on the hormonal regulation of pharyngeal pumping and muscle contraction, two key areas of anthelmintic development, and muscle metabolism, as well as key insights into how contraction and metabolism are linked.