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)

Chronic stimulation of cerebellar granule cells with N-methyl-D-aspartate (NMDA) or KCI induces a specific activation of the enzymes directly involved in glutamate neurotransmitter synthesis. Phosphate-activated glutaminase (PAG) activity is enhanced in cultured granule neurons incubated with 150 microM NMDA or 25 mM KCI. Other enzymes are not affected by this treatment like lactate dehydrogenase (LDH) and glutamate dehydrogenase (GLDH), which is also a mitochondrial enzyme but not directly involved in neurotransmitter synthesis. This effect is dependent on protein synthesis and is induced after 12 hr of NMDA or KCI stimulation. Kinetics of PAG activity showed that Km values were unaffected, in contrast to Vmax values that were increased approximately 70% and 215% over control by NMDA and KCI treatment, respectively. For GLDH, we found two isoforms that were affected differentially by the experimental conditions. Western blot analysis clearly evidenced an increase of approximately 120-180% in the amount of PAG in NMDA- and KCI-treated cells, whereas GLDH was not significantly modified. These results demonstrate that the NMDA- and KCI-induced activation of PAG are not due to the modification of the preexisting enzyme, but to an increase in the synthesis of this enzyme. This suggests that NMDA receptor stimulation during critical periods of the cerebellar granule cell development leads to the activation of gene expression involved in the process of cell differentiation.
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PMID:Characterization of the activation of glutaminase induced by N-methyl-D-aspartate and potassium in cerebellar granule cells. 887 28

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