Response of nucleoside diphosphate kinase to the adenylate energy charge

Thompson, Frances M.; Atkinson, Daniel E.

doi:10.1016/0006-291x(71)90201-4

Cited by 44 publications

(15 citation statements)

References 6 publications

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“…However, there have been no studies on how and to what extent the GTP/GMP ratio affects or controls metabolic processes. Even though the role of the guanine nucleotides in yeast metabolism has been less explored than that of the adenine nucleotides, it is clear that the biochemical processes in which these nucleotides participate are required for both growth and survival [86,87]. Recent studies have shown that an imbalance in the guanine nucleotide pool can have detrimental effects on nitrogen metabolism, protein synthesis, viability and proliferation of yeast cells [78,79,88,89].…”

Section: Discussionmentioning

confidence: 99%

Dynamic metabolomics differentiates between carbon and energy starvation in recombinant Saccharomyces cerevisiae fermenting xylose

Bergdahl

Heer

Sauer

et al. 2012

Biotechnol Biofuels

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BackgroundThe concerted effects of changes in gene expression due to changes in the environment are ultimately reflected in the metabolome. Dynamics of metabolite concentrations under a certain condition can therefore give a description of the cellular state with a high degree of functional information. We used this potential to evaluate the metabolic status of two recombinant strains of Saccharomyces cerevisiae during anaerobic batch fermentation of a glucose/xylose mixture. Two isogenic strains were studied, differing only in the pathways used for xylose assimilation: the oxidoreductive pathway with xylose reductase (XR) and xylitol dehydrogenase (XDH) or the isomerization pathway with xylose isomerase (XI). The isogenic relationship between the two strains ascertains that the observed responses are a result of the particular xylose pathway and not due to unknown changes in regulatory systems. An increased understanding of the physiological state of these strains is important for further development of efficient pentose-utilizing strains for bioethanol production.ResultsUsing LC-MS/MS we determined the dynamics in the concentrations of intracellular metabolites in central carbon metabolism, nine amino acids, the purine nucleotides and redox cofactors. The general response to the transition from glucose to xylose was increased concentrations of amino acids and TCA-cycle intermediates, and decreased concentrations of sugar phosphates and redox cofactors. The two strains investigated had significantly different uptake rates of xylose which led to an enhanced response in the XI-strain. Despite the difference in xylose uptake rate, the adenylate energy charge remained high and stable around 0.8 in both strains. In contrast to the adenylate pool, large changes were observed in the guanylate pool.ConclusionsThe low uptake of xylose by the XI-strain led to several distinguished responses: depletion of key metabolites in glycolysis and NADPH, a reduced GTP/GDP ratio and accumulation of PEP and aromatic amino acids. These changes are strong indicators of carbon starvation. The XR/XDH-strain displayed few such traits. The coexistence of these traits and a stable adenylate charge indicates that xylose supplies energy to the cells but does not suppress a response similar to carbon starvation. Particular signals may play a role in the latter, of which the GTP/GMP ratio could be a candidate as it decreased significantly in both strains.

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Section: Discussionmentioning

confidence: 99%

Dynamic metabolomics differentiates between carbon and energy starvation in recombinant Saccharomyces cerevisiae fermenting xylose

Bergdahl

Heer

Sauer

et al. 2012

Biotechnol Biofuels

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“…Decrease in ATP concentration result in increases in ADP and more so in AMP, but without drastic changes in the overall energy charge. In normal brain tissue the energy charge is closer to 0.85 (Derr and Zieve, 1972) and is regulated by direct participation of adenine nucleotides in energy converting processes such as glycolysis, oxidative phosphorylation and in many energy-expending biosynthetic pathways such as those of amino acids, nucleic acids, protein, fatty acids and cholesterol synthesis (Thompson and Atkinson, 1971). Ketamine has been shown to alter the glucose utilization and thus the regional metabolism in brain (Crosby et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Delta oscillations induced by ketamine increase energy levels in sleep-wake related brain regions

et al. 2011

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Neuronal signaling consumes much of the brain energy, mainly through the restoration of the membrane potential (MP) by ATP-consuming ionic pumps. We have reported that, compared with waking, ATP levels increase during the initial hours of natural slow-wave sleep, a time with prominent EEG delta oscillations (0.5-4.5Hz). We have hypothesized that there is a delta oscillation-ATP increase coupling, since, during delta waves, neurons exhibit a prolonged hyperpolarizing phase followed by a very brief phase of action potentials. However, direct proof of this hypothesis is lacking, and rapid changes in EEG/ neuronal activity preclude measurement in the naturally sleeping brain. Thus, to induce a uniform state with pure delta oscillations and one previously shown to be accompanied by a similar pattern of neuronal activity during delta waves as natural sleep, we used ketamine-xylazine treatment in rats. We here report that, with this treatment, the high energy molecules ATP and ADP increased in frontal and cingulate cortices, basal forebrain, and hippocampus compared with spontaneous waking. Moreover, the degree of ATP increase positively and significantly correlated with the degree of EEG delta-activity. Supporting the hypothesis of decreased ATP consumption during delta activity, the ATP-consuming Na+-K+-ATPase mRNA levels were significantly decreased whereas the mRNAs for the ATP-producing cytochrome c oxidase (COX) subunits COX III and COX IVa were unchanged. Taken together, these data support the hypothesis of a cortical delta oscillation-dependent reduction in ATP consumption, thus providing the brain with increased ATP availability, and likely occurring because of reduced Na+-K+-ATPase related energy consumption.

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“…It has been demonstrated that in vitro the activity of NDP kinase from bovine liver (as measured by the transfer of the high-energy phosphate from ATP to GDP) responds to the energy charge of the adenylate pool, i.e., (ATP ϩ 1/2 ADP)/ (ATP ϩ ADP ϩ AMP) (30). A decrease in the energy charge results in a sharp decrease in the activity of NDP kinase and thereby a decrease in the control of the transfer of phosphate from ATP to other nucleotide pools.…”

Section: Discussionmentioning

confidence: 99%

Nucleoside diphosphate kinase from Escherichia coli

et al. 1995

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Nucleoside diphosphate (NDP) kinase from Escherichia coli was purified to homogeneity and was crystallized. Gel filtration analysis of the purified enzyme indicated that it forms a tetramer. The enzyme was phosphorylated with [␥-32 P]ATP, and the pH stability profile of the phosphoenzyme indicated that two different amino acid residues were phosphorylated. Both a histidine residue and serine residues, including Ser-119 and Ser-121, appear to be phosphorylated. A Ser119Ala/Ser121Ala double mutant (i.e., with a Ser-toAla double mutation at positions 119 and 121), as well as Ser119Ala and Ser121Ala mutants, was isolated. All of these retained NDP kinase activity; also, both the Ser119Ala and Ser121Ala mutants could still be autophosphorylated. In the case of the double mutant, a slight autophosphorylation activity, which was resistant to acid treatment, was still detected, indicating that an additional minor autophosphorylation site besides Nucleoside diphosphate (NDP) kinase catalyzes the following transphosphorylation reaction, via the formation of a phosphoenzyme intermediate:The primary role of NDP kinase in the cell was considered the maintenance of a pool of nucleotide triphosphates for the synthesis of DNA and RNA (22). NDP kinase was reported to be the only enzyme responsible for the synthesis of nucleotides other than ATP in Salmonella typhimurium (7). Also, the ndk gene appears to be essential in the gram-negative bacterium Myxococcus xanthus (20). Recently the enzyme has been implicated as a tumor suppressor candidate in studies of highly metastatic human cells (14,26,27) and has been associated with the development of Drosophila larvae (3,25).NDP kinase genes (ndk) from prokaryotic and eukaryotic organisms have been cloned and sequenced (8,19). The deduced amino acid sequence of the enzyme from Escherichia coli indicated that NDP kinases are highly conserved throughout evolution; the E. coli and human (Nm23-H1) enzymes are 43% identical (8). The three-dimensional structures of NDP kinases from Dictyostelium discoideum (4), M. xanthus (33), and Drosophila melanogaster (2) have been determined. These studies again showed that NDP kinases from different sources share highly conserved three-dimensional structures.NDP kinases are known to function by a ping-pong mechanism which involves the formation of a high-energy phosphoenzyme intermediate. Most of the intermediates have been shown to be alkali stable and acid labile, suggesting the formation of phosphohistidine, which has been identified in NDP kinases from various sources (22). Recently, histidine 118 has been identified as the phosphorylation site in one of the human NDP kinases, Nm23 (6). This histidine residue is invariant among all the NDP kinases sequenced so far (8). However phospho-NDP kinases with drastically different stability characteristics have been reported (22). Phosphoserine formation has been reported to occur in NDP kinase from rat mucosal mast cells (11) and in NDP kinase from M. xanthus, in which the formation of phosphohistidine ha...

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Response of nucleoside diphosphate kinase to the adenylate energy charge

Cited by 44 publications

References 6 publications

Dynamic metabolomics differentiates between carbon and energy starvation in recombinant Saccharomyces cerevisiae fermenting xylose

Dynamic metabolomics differentiates between carbon and energy starvation in recombinant Saccharomyces cerevisiae fermenting xylose

Delta oscillations induced by ketamine increase energy levels in sleep-wake related brain regions

Nucleoside diphosphate kinase from Escherichia coli

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