Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The African sharptooth catfish Clarias gariepinus lives in freshwater, is an obligatory air-breather, and can survive on land during drought. The objective of this study was to elucidate the mechanism of acute ammonia toxicity in C. gariepinus, and to examine whether methionine sulfoximine [MSO; an inhibitor of glutamine synthetase (GS)] or MK801 [an antagonist of N-methyl d-aspartate type glutamate (NMDA) receptors] had protective effects against acute ammonia toxicity in this fish. After 48 h of exposure to a sublethal concentration (75 mmoll(-1)) of environmental ammonia, the brain glutamine and ammonia contents in C. gariepinus increased to 15 micromol g(-1) and 4 micromol g(-1), respectively. Thus, C. gariepinus detoxified ammonia to glutamine and could tolerate high levels of glutamine in its brain. After C. gariepinus was injected intraperitoneally with a sublethal dose of ammonium acetate (CH(3)COONH(4); 8 micromol g(-1) fish) followed with emersion, brain ammonia and glutamine contents increased continuously during the subsequent 24-h period, reaching 7 and 18 micromol g(-1), respectively, at hour 24. These results suggest that when confronted with acute ammonia toxicity, the survival of C. gariepinus was crucially determined by its high tolerance of ammonia and high capacity to detoxify ammonia to glutamine in the brain. For fish injected with a sublethal dose of CH(3)COONH(4) (10 micromol g(-1) fish) followed with immersion, there were transient but significant increases in brain ammonia and glutamine contents, which peaked at hour 2 (4 micromol g(-1)) and hour 6 (6 micromol g(-1)), respectively. From these results, it can be deduced that C. gariepinus accumulated glutamine in preference to ammonia in its brain. By contrast, for fish injected with a lethal dose (20 micromol g(-1) fish) of CH(3)COONH(4) followed with immersion, the brain ammonia content increased drastically to 10 micromol g(-1) after 30 min, while the brain glutamine content remained relatively low at 5 micromol g(-1). Therefore, it can be concluded that increased synthesis and accumulation of glutamine in the brain was not the major cause of death in C. gariepinus confronted with acute ammonia toxicity. The determining factor of acute ammonia toxicity appeared to be the rate of ammonia build-up in the brain. MK801 (2 microg g(-1) fish) had no protective effect on C. gariepinus injected with a lethal dose of CH(3)COONH(4) (20 micromol g(-1) fish) indicating that activation of NMDA receptors might not be involved. By contrast, the prior administration of MSO (100 microg g(-1) fish) reduced the mortality rate from 100% to 80% and at the same time prolonged the time of death significantly from 27 min to 48 min. However, the protective effect of MSO was apparently unrelated to the inhibition of glutamine synthetase and prevention of glutamine accumulation in the brain. Instead, MSO affected activities of glutamate dehydrogenase and alanine aminotransferase and suppressed the rate of ammonia build up in the brain of fish injected with a lethal dose of CH(3)COONH(4).
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PMID:Ammonia toxicity and tolerance in the brain of the African sharptooth catfish, Clarias gariepinus. 1738 43

The objective of this study was to elucidate the mechanisms of acute ammonia toxicity in the aquatic Chinese soft-shelled turtle, Pelodiscus sinensis, and to examine how this turtle defended against a sublethal dose of NH(4)Cl injected into its peritoneal cavity. The ammonia and glutamine contents in the brains of turtles that succumbed within 3h to an intraperitoneal injection with a lethal dose (12.5 micromolg(-1) turtle) of NH(4)Cl were 21 and 4.4 micromolg(-1), respectively. Since the brain glutamine content increased to 8 micromolg(-1) at hour 6 and recovered thereafter in turtles injected with a sub-lethal dose of NH(4)Cl (7.5 micromolg(-1) turtle), it can be concluded that increased glutamine synthesis and accumulation was not the major cause of acute ammonia toxicity in P. sinensis. Indeed, the administration of l-methionine S-sulfoximine (MSO; 82 microgg(-1) turtle), a glutamine synthetase (GS) inhibitor, prior to the injection of a lethal dose of NH(4)Cl had no significant effect on the mortality rate. Although the prior administration of MSO led to an extension of the time to death, it was apparently a result of its effects on glutamate dehydrogenase and glutamate formation, instead of glutamine synthesis and accumulation, in the brain. By contrast, a prior injection with MK801 (1.6 microgg(-1) turtle), a NMDA receptor antagonist, reduced the 24h mortality of turtles injected with a lethal dose of NH(4)Cl by 50%. Thus, acute ammonia toxicity in P. sinensis was probably a result of glutamate dysfunction and the activation of NMDA receptors. NMDA receptor activation could also be exacerbated through membrane depolarization caused by the extraordinarily high level of ammonia (21 micromolg(-1) brain) in the brain of turtles that succumbed to a lethal dose of NH(4)Cl. One hour after the injection with a sub-lethal dose of NH(4)Cl, the brain of P. sinensis exhibited an extraordinarily high tolerance of ammonia (16 micromolg(-1) brain). The transient nature of ammonia accumulation indicates that P. sinensis could ameliorate ammonia toxicity through the suppression of endogenous ammonia production and/or the excretion of exogenous ammonia. Despite being ureogenic and ureotelic, only a small fraction of the exogenous ammonia was detoxified to urea. A major portion of ammonia was excreted unchanged, resulting in an apparent ammonotely in the experimental turtles. Since there were increases in total essential free amino acid contents in the brain, liver and muscle, it can be deduced that a suppression of amino acid catabolism had occurred, reducing the production of endogenous ammonia and hence alleviating the possibility of ammonia intoxication.
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PMID:Mechanisms of and defense against acute ammonia toxicity in the aquatic Chinese soft-shelled turtle, Pelodiscus sinensis. 1806 26

Changes in glutamatergic nervous activities following intracerebroventricular (icv) administration of ethylcholine aziridinium (AF64A) were studied in rats. The levels of total glutamate, those of glutamate in cerebrospinal fluid (CSF) and in extracellular fluid (ECF) of striatum, the activities of glutamine synthetase (GS), glutaminase and glutamate dehydrogenase (GDH) and the specific binding sites of [(3)H]MK801 in striatum, hippocampus and frontal cortex were assessed a week after the infusion of AF64A (3 nmol) into lateral ventricle. The levels of total glutamate were significantly decreased in striatum, hippocampus and frontal cortex after AF64A treatment. Although the levels of glutamate in CSF weren't changed after AF64A treatment, the levels of glutamate in ECF of striatum were significantly decreased (62.6%). GS activities in striatum were significantly decreased. But, glutaminase activities in striatum were significantly increased. However, the activities of GS and glutaminase in frontal cortex and hippocampus weren't changed. Although GDH activities in frontal cortex were significantly decreased, those in striatum and hippocampus weren't altered. The striatal densities of [(3)H]MK 801 binding sites were increased without changes in its affinity. Also, the specific binding sites of [(3)H]MK801 were increased in frontal cortex but not in hippocampus. These results indicate that the glutamatergic nervous activities were altered with the infusion of AF64A into lateral ventricle. Furthermore, it suggest that the decreased levels of glutamate after AF64A treatment may affect the change in the other parameters of glutamatergic neuronal activities.
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PMID:Effects of I.C.V. administration of ethylcholine aziridinium (AF64A) on the central glutamatergic nervous systems in rats. 1897 10