13N as a tracer for studying glutamate metabolism.
13N as a tracer for studying glutamate metabolism.
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DOI：
10.1016/j.neuint.2010.11.011
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发表时间：
2011-09
影响因子：
4.2
通讯作者：
Cooper, Arthur J. L.
中科院分区：
文献类型：
--
作者：
Cooper, Arthur J. L.
关键词：
这篇小型综述总结了我和我的同事们所进行的与本卷主题[即谷氨酸脱氢酶（GDH）]相关的研究，这些研究使用放射性¹³N（半衰期为9.96分钟）作为生物示踪剂。这些研究揭示了此前未被认识到的体内某些代谢物之间氮交换的快速性。例如，我们的工作表明：a）在大鼠肝脏中，门静脉氨转化为尿素的半衰期约为10 - 11秒，尽管这需要五个酶催化步骤和两个线粒体转运步骤；b）麻醉大鼠血液中氨的停留时间≤7 - 8秒；c）在正常大鼠大脑中，血氨掺入谷氨酰胺的半衰期<3秒；d）大鼠肝脏中谷氨酸和天冬氨酸氮之间的平衡极其迅速（以秒计），这反映了肝脏天冬氨酸氨基转移酶反应的各组分处于热力学平衡这一事实。我们的工作强调了大鼠肝脏中GDH反应作为根据需要异化或同化氨的通道的重要性。相比之下，我们的工作表明，大鼠大脑中的GDH反应似乎主要朝着产生氨（异化）的方向进行。讨论了GDH反应作为大脑内源性氨源的重要性以及GDH与大脑谷氨酰胺循环的关系。最后，我们的工作与正电子发射断层扫描（PET）和核磁共振（NMR）的日益广泛应用相结合，分别用于研究正常个体以及肝病或其他与高氨血症相关疾病患者的大脑氨摄取和大脑谷氨酰胺情况。
This mini-review summarizes studies my associates and I carried out that are relevant to the topic of the present volume [i.e. glutamate dehydrogenase (GDH)] using radioactive 13N (t½ 9.96 min) as a biological tracer. These studies revealed the previously unrecognized rapidity with which nitrogen is exchanged among certain metabolites in vivo. For example, our work demonstrated that a) the t½ for conversion of portal vein ammonia to urea in the rat liver is ~10–11 sec, despite the need for five enzyme-catalyzed steps and two mitochondrial transport steps, b) the residence time for ammonia in the blood of anesthetized rats is ≤7–8 sec, c) the t½ for incorporation of blood-borne ammonia into glutamine in the normal rat brain is <3 sec, and d) equilibration between glutamate and aspartate nitrogen in rat liver is extremely rapid (seconds), a reflection of the fact that the components of the hepatic aspartate aminotransferase reaction are in thermodynamic equilibrium. Our work emphasizes the importance of the GDH reaction in rat liver as a conduit for dissimilating or assimilating ammonia as needed. In contrast, our work shows that the GDH reaction in rat brain appears to operate mostly in the direction of ammonia production (dissimilation). The importance of the GDH reaction as an endogenous source of ammonia in the brain and the relation of GDH to the brain glutamine cycle is discussed. Finally, our work integrates with the increasing use of positron emission tomography (PET) and nuclear magnetic resonance (NMR) to study brain ammonia uptake and brain glutamine, respectively, in normal individuals and in patients with liver disease or other diseases associated with hyperammonemia.
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影响因子：
4.7
作者：
CHEE, PY;DAHL, JL;FAHIEN, LA
通讯作者：
FAHIEN, LA
影响因子：
4.7
作者：
COOPER, AJL;MORA, SN;GELBARD, AS
通讯作者：
GELBARD, AS
影响因子：
13.5
作者：
Ahl, B;Weissenborn, K;Burchert, W
通讯作者：
Burchert, W
影响因子：
4.7
作者：
García-Espinosa, María A.;Wallin, Reidar;Sweatt, Andrew J.
通讯作者：
Sweatt, Andrew J.
DOI：
10.1046/j.1432-1033.2002.03018.x
发表时间：
2002-07-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
del Arco, A;Morcillo, J;Satrústegui, J
通讯作者：
Satrústegui, J