Ratnakumari L, Murthy C R
School of Life Sciences, University of Hyderabad, India.
Neurochem Res. 1989 Mar;14(3):221-8. doi: 10.1007/BF00971314.
Activity levels of pyruvate dehydrogenase, enzymes of citric acid cycle, aspartate and alanine aminotransferases were estimated in mitochondria, synaptosomes and cytosol isolated from brains of normal rats and those injected with acute and subacute doses of ammonium acetate. In mitochondria isolated from animals treated with acute dose of ammonium acetate, there was an elevation in the activities of pyruvate, isocitrate and succinate dehydrogenases while the activities of malate dehydrogenase (malate----oxaloacetate), aspartate and alanine aminotransferases were suppressed. In subacute conditions a similar profile of change was noticed excepting that there was an elevation in the activity of alpha-ketoglutarate dehydrogenase in mitochondria. In the synaptosomes isolated from animals administered with acute dose of ammonium acetate, there was an increase in the activities of pyruvate, isocitrate, alpha-ketoglutarate and succinate dehydrogenases while the changes in the activities of malate dehydrogenase, aspartate and alanine amino transferases were suppressed. In the subacute toxicity similar changes were observed in this fraction except that the activity of malate dehydrogenase (oxaloacetate----malate) was enhanced. In the cytosol, pyruvate dehydrogenase and other enzymes of citric acid cycle except malate dehydrogenase were enhanced in both acute and subacute ammonia toxicity though their activities are lesser than that of mitochondria. In this fraction malate dehydrogenase (oxaloacetate----malate) was enhanced while activities of malate dehydrogenase (malate----oxaloacetate), aspartate and alanine aminotransferases were suppressed in both the conditions. Based on these results it is concluded that the decreased activities of malate dehydrogenase (malate----oxaloacetate) in mitochondria and of aspartate aminotransferase in mitochondria and cytosol may be responsible for the disruption of malate-aspartate shuttle in hyperammonemic state.(ABSTRACT TRUNCATED AT 250 WORDS)
在从正常大鼠以及注射了急性和亚急性剂量醋酸铵的大鼠脑中分离出的线粒体、突触体和细胞溶质中，对丙酮酸脱氢酶、柠檬酸循环的酶、天冬氨酸和丙氨酸转氨酶的活性水平进行了评估。在从用急性剂量醋酸铵处理的动物中分离出的线粒体中，丙酮酸、异柠檬酸和琥珀酸脱氢酶的活性升高，而苹果酸脱氢酶（苹果酸→草酰乙酸）、天冬氨酸和丙氨酸转氨酶的活性受到抑制。在亚急性条件下，除了线粒体中α-酮戊二酸脱氢酶的活性升高外，也观察到了类似的变化模式。在从用急性剂量醋酸铵处理的动物中分离出的突触体中，丙酮酸、异柠檬酸、α-酮戊二酸和琥珀酸脱氢酶的活性增加，而苹果酸脱氢酶、天冬氨酸和丙氨酸转氨酶的活性变化受到抑制。在亚急性毒性情况下，在该部分中观察到了类似的变化，只是苹果酸脱氢酶（草酰乙酸→苹果酸）的活性增强。在细胞溶质中，在急性和亚急性氨毒性情况下，丙酮酸脱氢酶和柠檬酸循环的其他酶（除苹果酸脱氢酶外）均增强，尽管它们的活性低于线粒体中的活性。在该部分中，苹果酸脱氢酶（草酰乙酸→苹果酸）增强，而在这两种情况下，苹果酸脱氢酶（苹果酸→草酰乙酸）、天冬氨酸和丙氨酸转氨酶的活性均受到抑制。基于这些结果，可以得出结论，线粒体中苹果酸脱氢酶（苹果酸→草酰乙酸）以及线粒体和细胞溶质中天冬氨酸转氨酶活性的降低可能是高氨血症状态下苹果酸-天冬氨酸穿梭破坏的原因。（摘要截取自250字）
