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 principal initial product of metabolism of 13N-labeled ammonium by Anabaena cylindrica grown with either NH4+ or N2 as nitrogen source is amide-labeled glutamine. The specific activity of glutamine synthetase is approximately half as great in NH4+-grown as in N2-grown filaments. After 1.5 min of exposure to 13NH4+, the ratio of 13N in glutamate to 13N in glutamine reaches a value of approximately 0.1 for N2- and 0.15 for NH4+-grown filaments, whereas after the same period of exposure to [13N]N2, that ratio has reached a value close to unity and is rising rapidly. During pulse-chase experiments, 13N is transferred from the amide group to glutamine into glutamate, and then apparently into the alpha-amino group of glutamine. Methionine sulfoximine, an inhibitor of glutamine synthetase, inhibits the formation of glutamine. In the presence of the inhibitor, direct formation of glutamate takes place, but accounts for only a few per cent of the normal rate of formation of that amino acid; and alanine is formed about as rapidly as glutamate. Azaserine reduces formation of [13N]glutamate approximately 100-fold, with relatively little effect on the formation of [13N]glutamine. Aminooxyacetate, an inhibitor of transaminase reactions blocks transfer of 13N to aspartate, citrulline, and arginine. We conclude, on the basis of these results and others in the literature, that the glutamine synthetase/glutamate synthase pathway mediates most of the initial metabolism of ammonium in A. cylindrica, and that glutamic acid dehydrogenase and alanine dehydrogenase have only a very minor role.
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PMID:The pathways of assimilation of 13NH4+ by the cyanobacterium, Anabaena cylindrica. 41 Aug 9

The principal initial product of metabolism of [13N]N2 and 13NH4+ by five diverse cyanobacteria is glutamine. Methionine sulfoximine inhibits formation of [13N]glutamine except in the case of Gloeothece sp., an organism with a thick sheath through which the inhibitor may not penetrate. Thus, glutamine synthetase appears to catalyze the initial step in the assimilation of N2-derived or exogenous NH4+ by these organisms. [13N]Glutamate is, in all cases, the second major product of assimilation of 13N-labeled N2 and NH4+. In all of the N2-fixing cyanobacteria studied, the fraction of 13N in glutamine declines and that in glutamate increases with increasing times of assimilation of [13N]N2 and 13NH4+, and (Gloeothece again excepted) methionine sulfoximine reduces incorporation of 13N into glutamate as well as into glutamine. Glutamate synthase therefore appears to catalyze the formation of glutamate in a wide range of N2-fixing cyanobacteria. However, the major fraction of [13N]glutamate formed by Anacystis nidulans incubated with 13NH4+ may be formed by glutamic acid dehydrogenase. The formation of [13N]alanine from 13NH4+ appears to be catalyzed principally either by alanine dehydrogenase (as in Cylindrospermum licheniforme) or by a transaminase (as in Anabaena variabilis).
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PMID:Pathways of assimilation of [13N]N2 and 13NH4+ by cyanobacteria with and without heterocysts. 41 57

Corynebacterium callunae (NCIB 10338) grows faster on glutamate than ammonia when used as sole nitrogen sources. The levels of glutamine synthetase (GS; EC 6.3.1.2) and glutamate synthase (GOGAT; EC 1.4.1.13) of C. callunae were found to be influenced by the nitrogen source. Accordingly, the levels of GS and GOGAT activities were decreased markedly under conditions of ammonia excess and increased under low nitrogen conditions. In contrast, glutamate dehydrogenase (GDH; EC 1.4.1.4) activities were not significantly affected by the type or the concentration of the nitrogen source supplied. The carbon source in the growth medium could also affect GDH, GS and GOGAT levels. Of the carbon sources tested in the presence of 2 mM or 10 mM ammonium chloride as the nitrogen source pyruvate, acetate, fumarate and malate caused a decrease in the levels of all three enzymes as compared with glucose. GDH, GS and GOGAT levels were slightly influenced by aeration. Also, the enzyme levels varied with the growth phase. Methionine sulfoximine, an analogue of glutamine, markedly inhibited both the growth of C. callunae cells and the transferase activity of GS. The apparent Km values of GDH for ammonia and glutamate were 17.2 mM and 69.1 mM, respectively. In the NADPH-dependent reaction of GOGAT, the apparent Km values were 0.1 mM for alpha-ketoglutarate and 0.22 mM for glutamine.
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PMID:The effect of various culture conditions on the levels of ammonia assimilatory enzymes of Corynebacterium callunae. 135 48

Methionine sulfoximine inhibits the growth of Salmonella typhimurium at a concentration of 50 muM, and the addition of glutamine, but not glutamate, is sufficient to overcome this inhibition. The analogue causes 50% inhibition of glutamine synthetase activity at 2 to 4 muM and of glutamate synthase at 2 to 3 mM when these enzymes are assayed in vitro. No inhibition of glutamate dehydrogenase activity is observed at analogue concentrations as high as 50 mM. Two mutants selected for their resistance to methionine sulfoximine inhibition have a partial growth requirement for glutamine and a reduction in the glutamine synthetase and glutamate synthase activities. The sensitivity of the remaining glutamine synthetase activity in these mutants to methionine sulfoximine inhibition appears unaltered, and the lesions conferring the analogue resistance may not affect glutamine synthetase directly.
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PMID:Characterization of Salmonella typhimurium strains sensitive and resistant to methionine sulfoximine. 415 9

L-Methionine sulfoximine (MSO) at concentration 1.25 mM in vivo causes the inhibition of glutamine synthetase (GS) in both roots and leaves of young seedlings of kidney bean following the accumulation of high levels of ammonia and decrease in amounts of free amino acids that is more pronounced in leaves. The inhibition of GS by MSO in leaves in the case of externally supplied 5 mM (15NH4)2SO4 assimilation leads to ammonia accumulation and the decrease in the amounts of glutamine and glutamic acid and the intensity of the incorporation of 15N into them. In roots the inhibition of GS is not followed by the decrease of 15N content into glutamate. It is concluded that the pathway of ammonia primary assimilation in leaves is via GS and glutamate synthase (GOGAT), while in roots glutamate dehydrogenase also plays an important role in this process.
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PMID:Effect of methionine sulfoximine on nitrogen metabolism and externally supplied ammonium assimilation in kidney bean. 879 22

Glutamine is the first major organic product of assimilation of (13)NH(4) (+) by tobacco (Nicotiana tabacum L. cv. Xanthi) cells cultured on nitrate, urea, or ammonium succinate as the sole source of nitrogen, and of (13)NO(3) (-) by tobacco cells cultured on nitrate. The percentage of organic (13)N in glutamate, and subsequently, alanine, increases with increasing periods of assimilation. (13)NO(3) (-), used for the first time in a study of assimilation of nitrogen, was purified by new preparative techniques. During pulse-chase experiments, there is a decrease in the percentage of (13)N in glutamine, and a concomitant increase in the percentage of (13)N in glutamate and alanine. Methionine sulfoximine inhibits the incorporation of (13)N from (13)NH(4) (+) into glutamine more extensively than it inhibits the incorporation of (13)N into glutamate, with cells grown on any of the three sources of nitrogen. Azaserine inhibits glutamate synthesis extensively when (13)NH(4) (+) is fed to cells cultured on nitrate. These results indicate that the major route for assimilation of (13)NH(4) (+) is the glutamine synthetase-glutamate synthase pathway, and that glutamate dehydrogenase also plays a role, but a minor one. Methionine sulfoximine inhibits the incorporation of (13)N from (13)NO(3) (-) into glutamate more strongly than it inhibits the incorporation of (13)N into glutamine, suggesting that the assimilation of (13)NH(4) (+) derived from (13)NO(3) (-) may be mediated solely by the glutamine synthetase-glutamate synthase pathway.
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PMID:Initial organic products of assimilation of [N]ammonium and [N]nitrate by tobacco cells cultured on different sources of nitrogen. 1666 May 6

The levels of glutamine synthetase (GS) and glutamate dehydrogenase (GDH) in Chlorella autotrophica (clone 580) are strongly regulated by the nitrogen source and salt concentration of the medium. GS is present at high levels in NO(3) (-)-grown cells, and at maximum levels in nitrogen-starved cells. However, the levels of GS in these cells are somewhat decreased by increasing salinity. Cells growing on NH(4) (+) have high NADPH-GDH activity, the levels of which increase with increasing NH(4) (+) supply, while GS decreases to a very low level under these conditions. Salinity intensifies the induction of NADPH-GDH activity in NH(4) (+)-grown cells. The levels of NADH-GDH are low in this alga, but present under all growth conditions. Methionine sulfoximine (MSX) has little effect on growth and nitrogen assimilation of the alga in the presence of NH(4) (+).
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PMID:Nitrogen Metabolism of the Marine Microalga Chlorella autotrophica. 1666 2

Fuel stimulation of insulin secretion from pancreatic beta-cells is thought to be mediated by metabolic coupling factors that are generated by energized mitochondria, including protons, adenine nucleotides, and perhaps certain amino acids (AA), as for instance aspartate, glutamate, or glutamine (Q). The goal of the present study was to evaluate the role of such factors when insulin release (IR) is stimulated by glucose or AA, alone or combined, using (31)P, (23)Na and (1)H NMR technology, respirometry, and biochemical analysis to study the metabolic events that occur in continuously superfused mouse beta-HC9 cells contained in agarose beads and enhanced by the phosphodiesterase inhibitor IBMX. Exposing beta-HC9 cells to high glucose or 3.5 mM of a physiological mixture of 18 AA (AAM) plus 2 mM glutamine caused a marked stimulation of insulin secretion associated with increased oxygen consumption, cAMP release, and phosphorylation potential as evidenced by higher phosphocreatine and lower P(i) peak areas of (31)P NMR spectra. Diazoxide blocked stimulation of IR completely, suggesting involvement of ATP-dependent potassium (K(ATP)) channels in this process. However, levels of MgATP and MgADP concentrations, which regulate channel activity, changed only slowly and little, whereas the rate of insulin release increased fast and very markedly. The involvement of other candidate coupling factors was therefore considered. High glucose or AAM + Q increased pH(i). The availability of temporal pH profiles allowed the precise computation of the phosphate potential (ATP/P(i) x ADP) in fuel-stimulated IR. Intracellular Na+ levels were greatly elevated by AAM + Q. However, glutamine alone or together with 2-amino-2-norbornanecarboxylic acid (which activates glutamate dehydrogenase) decreased beta-cell Na levels. Stimulation of beta-cells by glucose in the presence of AAM + Q (0.5 mM) was associated with rising cellular concentrations of glutamate and glutamine and strikingly lower aspartate levels. Methionine sulfoximine, an inhibitor of glutamine synthetase, blocked the glucose enhancement of AMM + Q-induced IR and associated changes in glutamine and aspartate but did not prevent the accumulation of glutamate. The results of this study demonstrate again that an increased phosphate potential and a functional K(ATP) channel are essential for metabolic coupling during fuel-stimulated insulin release but illustrate that determining the identity and relative importance of all participating coupling factors and second messengers remains a challenge largely unmet.
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PMID:Metabolic and ionic coupling factors in amino acid-stimulated insulin release in pancreatic beta-HC9 cells. 1726 32