Functional inhibition of cytosolic and mitochondrial aspartate aminotransferase by L-2-amino-4-methoxy-trans-3-butenoic acid in isolated rat hepatocytes and mitochondria.
Functional inhibition of cytosolic and mitochondrial aspartate aminotransferase by L-2-amino-4-methoxy-trans-3-butenoic acid in isolated rat hepatocytes and mitochondria.
复制标题
L-2-氨基-4-甲氧基-反式-3-丁烯酸对离体大鼠肝细胞和线粒体中胞浆和线粒体天冬氨酸转氨酶的功能性抑制。
DOI：
10.1016/0003-9861(81)90289-7
复制
发表时间：
1981
影响因子：
3.9
通讯作者：
R. Freedland
中科院分区：
文献类型：
--
作者：
S. B. Smith;R. Freedland
在与琥珀酸、氨和鸟氨酸孵育的离体大鼠肝线粒体中，转氨酶AMB-2-氨基-4-甲氧基-反式-3-丁烯酸（AMB）使天冬氨酸转氨酶活性降低约三分之二。在30分钟的孵育期内，线粒体的天冬氨酸生产不受影响，表明线粒体天冬氨酸转氨酶活性通常远远超过天冬氨酸生产的最大速率所需的活性。在大鼠肝细胞培养与乳酸，氨，和鸟氨酸的抑制天冬氨酸氨基转移酶的胞浆和线粒体同工酶AMB的存在下，氨和鸟氨酸部分阻断。当丙酮酸取代乳酸作为碳源与分离的肝细胞，氨和鸟氨酸的存在下阻止AMB的线粒体，但不是天冬氨酸转氨酶的胞质同工酶的抑制。尿素的形成与乳酸，氨，和鸟氨酸孵育的细胞是不受AMB，除非细胞预孵育的抑制剂之前，添加底物。然而，尿素形成的丙酮酸，氨，和鸟氨酸的存在下孵育的细胞被强烈抑制AMB，即使没有预孵育。结果提示丙酮酸对氨和鸟氨酸的促尿素生成作用与天冬氨酸转氨酶的胞浆同工酶有关。相反，乳酸引起的尿素生成的刺激主要涉及线粒体天冬氨酸转氨酶。
The transaminase inhibitorl-2-amino-4-methoxy-trans-3-butenoic acid (AMB) decreased aspartate aminotransferase activity by approximately two-thirds in isolated rat liver mitohondria incubated with succinate, ammonia, and ornithine. Aspartate production by the mitochondria was unaffected over the 30-min incubation period, indicating that mitochondrial aspartate aminotransferase activity is normally far in excess of that required for maximal rates of aspartate production. In rat hepatocytes incubated with lactate, ammonia, and ornithine the inhibition of both the cytosolic and mitochondrial isozymes of aspartate aminotransferase by AMB was partially blocked by the presence of ammonia and ornithine. When pyruvate was substituted for lactate as a carbon source with isolated hepatocytes, the presence of ammonia and ornithine blocked the inhibition by AMB of the mitochondrial but not the cytosolic isozyme of aspartate aminotransferase. Urea formation by cells incubated with lactate, ammonia, and ornithine was unaffected by AMB unless the cells were preincubated with the inhibitor prior to the addition of substrates. However, urea formation by cells incubated in the presence of pyruvate, ammonia, and ornithine was inhibited strongly by AMB even without preincubation. The results suggest that the stimulation of ureogenesis from ammonia and ornithine by pyruvate involves the cytosolic isozyme of aspartate aminotransferase. In contrast, the stimulation of ureogenesis elicited by lactate primarily involved mitochondrial aspartate aminotransferase.