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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both components of nitrogenase, dinitrogenase and dinitrogenase reductase, are rapidly inactivated by oxygen. To investigate the proteolytic degradation of dinitrogenase reductase irreversibly destroyed by high oxygen concentrations, we carried out in vitro experiments with heterocyst extracts from Anabaena variabilis ATCC 29413. The results indicate a direct dependence of degradation on the applied oxygen concentration. Although the degrees of degradation were similar for both the modified and unmodified subunits of dinitrogenase reductase, there was a significant difference with respect to the cleavage products observed. The pattern of effective protease inhibitors suggests the involvement of serine proteases with chymotrypsin- and trypsin-like specificity. A protective effect was obtained by saturation of the nucleotide binding sites of dinitrogenase reductase with either ATP or ADP. As shown by gel filtration experiments, the adenylates prevented the nitrogenase subunits from extensive noncovalent aggregation, which is usually considered evidence for a denaturing process. The in vitro degradation of dinitrogenase reductase is discussed in connection with previous reports on degradation of nitrogenase in cyanobacteria under oxygen stress and/or starvation.
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PMID:Proteolytic degradation of dinitrogenase reductase from Anabaena variabilis (ATCC 29413) as a consequence of ATP depletion and impact of oxygen. 855 Apr 89

In many pathogenic bacteria, iron starvation serves as an environmental signal that triggers the expression of virulence factors, many of which are found on the cell surface or secreted into the culture supernatant. Using the chelating agent nitrilotriacetic acid, we have established conditions for iron starvation of the important human pathogen Streptococcus pyogenes (the group A streptococcus) and determined that iron limitation results in the specific appearance of several new proteins in the culture supernatant. One of these supernatant proteins is the ADP-ribosylating protein known as streptococcal plasmin receptor (Plr) or as the streptococcal surface glyceraldehyde-3-phosphate-dehydrogenase because of its other activities. Upon iron starvation, Plr is specifically released into the culture supernatant in a time-dependent manner, and its appearance in the supernatant is not accompanied by induction of plr mRNA synthesis. Release of Plr from the bacteria may be important for the virulence of group A streptococci and the manifestation of diseases.
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PMID:Iron starvation causes release from the group A streptococcus of the ADP-ribosylating protein called plasmin receptor or surface glyceraldehyde-3-phosphate-dehydrogenase. 867 93

The native V1 complex of the tobacco hornworm vacuolar type ATPase (V-ATPase) was purified from cytosolic extracts of molting larval midgut. It consisted of the established V-ATPase subunits A, B, and E along with the 14-kDa subunit F and the novel 13-kDa subunit G. The final amount of purified V1 complex made up an unexpectedly high 2% of the total cytosolic protein, with a yield of approximately 0.4 mg/g of tissue. An equally high amount of cytosolic V1 complex was obtained from starving intermolt larvae. By contrast, the cytosolic V1 pool was reduced drastically in feeding intermolt larvae or in larvae that had been refed after starvation. The activity of the membrane-bound V-ATPase holoenzyme was inversely related to the size of the cytosolic V1 pool, suggesting that the insect plasma membrane V-ATPase is regulated by reversible disassembly of the V1 complex as a function of the feeding condition of the larvae. Like F1-ATPases, the purified V1 complex exhibited Ca2+-dependent ATPase activity and, in the presence of 25% methanol, exhibited Mg2+-dependent ATPase activity. Therefore, we designate the native V1 complex, V1-ATPase. Both enzyme activities were completely inhibited by micromolar N-ethylmaleimide. In contrast to the Ca2+-dependent V1-ATPase activity, the Mg2+/methanol-dependent V1-ATPase activity did not decrease with the incubation time and thus was not inhibited by ADP. Methanol appears to induce a conformational change of the V1 complex, leading to enzymatic properties of the V1-ATPase that are similar to those of the membrane-bound V-ATPase holoenzyme. This is the first time that a native and enzymatically active V1 complex has been purified from the cytosol.
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PMID:Purification and properties of a cytosolic V1-ATPase. 870 48

The cyanobacterium Synechocystis sp. PCC 6803 contains two genes encoding two different types of glutamine synthetases (GS), glnA and glnN. The first codes for a typical prokaryotic GS type I and the second one codes for a GS type III, different in amino acid sequence to the prokaryotic GSI and the eukaryotic GSII. The glnN gene has been expressed in Escherichia coli and the corresponding protein purified almost to homogeneity (92%). The native enzyme (500 kDa) was composed of six identical subunits with an apparent molecular mass of 80 kDa. The protein was strongly stabilized in the presence of Mn2+ but not with other divalent cations. Biosynthetic activity of GSIII required the same substrates and cofactors as GSI and GSII enzymes. Apparent Km values for ATP, glutamate and ammonium were 0.43 mM, 0.9 mM and 0.19 mM, respectively. The enzyme was weakly inhibited by several amino acids and strongly inhibited by ADP. Synechocystis GSIII was also inhibited by L-methionine sulfoximine and DL-phosphinotricin, two transition-state analogs of the GS reaction mechanism. GSIII has also been purified from nitrogen-starved Synechocystis 6803 glnA mutant cells, demonstrating that the GS activity, strongly induced under nitrogen starvation in these cells, corresponds to the glnN gene product. In addition, a Synechocystis 6803 glnN mutant lacks the corresponding 80-kDa protein (GSIII). Polyclonal antibodies specific for GSIII cross-react with GSIII from other cyanobacteria. In all the strains analysed, levels of GSIII protein increased under nitrogen deficiency. These data suggest that GSIII is specifically required under conditions of nitrogen starvation.
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PMID:Purification and characterization of a new type of glutamine synthetase from cyanobacteria. 906 72

The regulation of amino acid transport from the vacuolar reservoir into the cytoplasm has been studied in hyphal cells of Penicillium cyclopium. To avoid artifacts caused by the isolation of vacuoles, efflux was examined "in situ," i.e. in cells whose plasma membranes were permeabilized for micromolecules by a treatment with nystatin. The ATP-dependent proton gradient and amino acid transport activities at the vacuolar membrane remained intact under these conditions. Accumulation of amino acids in the vacuole proved to be the result of a dynamic equilibrium of active, ATP-dependent uptake and energy-independent efflux. The latter was strongly accelerated after the vacuolar amino acid content had surpassed a threshold level. Efflux of vacuolar amino acids was specifically controlled by extravacuolar adenylates: ATP, 5'-adenylyl imidodiphosphate (an ATPase-resistant ATP-analogue), ADP, or AMP caused a strong inhibition in the concentration range around 200 micromol/liter, whereas both lower and higher concentrations allowed significant efflux rates. Estimates of the cytosolic adenylates (which consisted mainly of ATP) were close to 2 mmol/liter in glucose-metabolizing cells, which concentration allowed maximum rates of both vacuolar uptake and efflux. During 24 h of carbon and nitrogen starvation, the adenylate level decreased toward the efflux-inhibiting region around 200 micromol/liter, whereas 3-4 d of carbon and nitrogen starvation caused a further decline of the adenylate content, leading again to efflux-permitting concentrations. Thus, the cytosolic adenylate pool appears to effectively control the availability of vacuolar amino acids for the cellular metabolism.
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PMID:Dynamic compartmentation of vacuolar amino acids in Penicillium cyclopium. Cytosolic adenylates act as a control signal for efflux into the cytosol. 918 83

Four mitochondrial protein kinases have been cloned. These proteins represent a new family of protein kinases, related by sequence to the bacterial protein kinases but by function to the eukaryotic serine protein kinases. Arg288 is required for recognition by BCKDK of the phosphorylation site on the E1alpha subunit of the BCKDH complex. BCKDK inhibits the dehydrogenase activity of the BCKDH complex by introducing a negative charge into the active-site pocket of the E1 component. Protein starvation of rats induces an increase in the amount of BCKDK bound to the BCKDH complex. This causes inactivation of the BCKDH complex and conserves branched-chain amino acids for protein synthesis in the protein-starved state. Expression of the different PDK isoenzymes is tissue specific, and the different PDK isoenzymes are unique with respect to kinetic parameters for ATP and ADP and sensitivity to allosteric effectors (NADH, NAD+, coenzyme A, acetyl-CoA, pyruvate, and dichloroacetate). Preliminary experiments indicate that an increased amount of PDK2 protein partly explains the increase in PDK activity that occurs in rat liver in response to chemically induced diabetes.
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PMID:Mitochondrial alpha-ketoacid dehydrogenase kinases: a new family of protein kinases. 934 45

The kdpFABC operon, which encodes the structural genes for the high affinity K+ transport complex KdpFABC, is regulated by the sensor kinase KdpD and the response regulator KdpE. KdpD is a bifunctional enzyme catalyzing the autophosphorylation by ATP and the dephosphorylation of the corresponding response regulator KdpE. Here, we demonstrate that the phosphatase activity of KdpD is dependent on ATP, whereas GTP, ITP, CTP, ADP, and GDP have no effect. The phosphatase activity requires only ATP binding, because nonhydrolyzable analogs (adenosine-5'-[gamma-thio]triphosphate and adenosine-5'-[beta,gamma-imido]triphosphate) work as well. However, KdpD proteins missing amino acids 12-128 are characterized by a phosphatase activity that is independent of ATP. These proteins are still able to respond to K+ starvation, but an increase in osmolarity is no longer sensed. Comparison of different KdpD sequences reveals a conserved motif in this amino acid region that is very similar to a classical ATP-binding site (Walker A motif). Replacement of the conserved Gly37, Lys38, and Thr39 residues in the consensus ATP-binding sequence results in a KdpD protein that causes a kdpFABC expression pattern comparable with that seen with KdpD proteins missing amino acids 12-128. However, in vitro phosphatase activity is comparable with that of wild-type KdpD. These results suggest that amino acids 12-128 of KdpD are important for its activity and that an additional ATP-binding site in the N-terminal region seems to be involved in modulation of the phosphatase activity.
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PMID:Truncation of amino acids 12-128 causes deregulation of the phosphatase activity of the sensor kinase KdpD of Escherichia coli. 965 26

The influence of aeration and glucose feeding on the stability of recombinant protein A in Escherichia coli during the transition period from a fed-batch cultivation to downstream processing was studied. Neither interruption of the feeding under aerobic conditions nor anaerobic conditions in presence of glucose could stabilize protein A completely and the intracellular ATP pool did not decrease to less than 0.75-1 mM by this treatment. On the other hand, the absence of both oxygen and glucose resulted in a decrease of the ATP pool to less than 0.5 mM and almost complete stabilization of protein A. The decrease of ATP was more severe when sulfite was used instead of nitrogen gas to create anaerobic conditions in presence of glucose. This also resulted in nearly complete stabilization of protein A, which might be explained by an inhibiting effect of sodium sulfite on fermentation. Therefore, protein stabilization and decrease of the ATP pool were correlated in experiments in vivo. The concentrations of ADP and AMP increased during starvation and may also play a role in stabilization of the protein in vivo. ATP may be a limiting factor of proteolysis also during further steps of downstream processing. Its concentration decreases by 80-90% during harvesting and centrifugation of biomass and even further during disruption of cells. However, neither addition nor regeneration of ATP in cell disintegrate was enough to restore degradation of protein A, indicating that an additional factor limits proteolysis in vitro.
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PMID:Stabilization of a proteolytically sensitive cytoplasmic recombinant protein during transition to downstream processing. 995 28

In Escherichia coli the enzyme guanosine kinase phosphorylates guanosine to GMP, which is further phosphorylated to GDP and GTP by other enzymes. Here I report that guanosine kinase is subject to efficient feedback inhibition by the end product of the pathway, GTP, and that this regulation is abolished by a previously described mutation, gsk-3, in the structural gene for guanosine kinase (Hove-Jensen, B., and Nygaard, P. (1989) J. Gen. Microbiol. 135, 1263-1273). Consequently, the gsk-3 mutant strain was extremely sensitive to guanosine, which caused the guanine nucleotide pools to increase dramatically, thereby initiating a cascade of metabolic changes that eventually led to growth arrest. By isolation and characterization of guanosine-resistant derivatives of the gsk-3 mutant, some of the crucial steps in this deleterious cascade of events were found to include the following: first, conversion of GMP to adenine nucleotides via GMP reductase, encoded by the guaC gene; second, inhibition of phosphoribosylpyrophosphate synthetase by an adenine nucleotide, presumably ADP, causing starvation for histidine, tryptophan, and pyrimidines, all of which require PRPP for their synthesis; third, accumulation of the regulatory nucleotide guanosine 5',3'-bispyrophosphate (ppGpp), a general transcriptional inhibitor synthesized by the relA gene product in response to amino acid starvation.
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PMID:Inhibition of cellular growth by increased guanine nucleotide pools. Characterization of an Escherichia coli mutant with a guanosine kinase that is insensitive to feedback inhibition by GTP. 1002 43

Nitrogen starvation enhances up to 8-fold the cellular level of the NADP+-dependent isocitrate dehydrogenase activity (isocitrate:NADP+ oxidoreductase (decarboxylating), IDH, EC 1.1.1.42) in the thermophilic filamentous non-N2-fixing cyanobacterium Phormidium laminosum. The enzyme was purified 650-fold to electrophoretic homogeneity from nitrogen-starved cells with an activity yield of 25% and a specific activity of 500 U (mg protein)-1. The native enzyme showed a pI of 5.9 and it was a dimer of 107 kDa consisting of two identical subunits of 53 kDa. The activity required the presence of a divalent metal cation as an essential activator, Mn2+ or Mg2+ being the most effective. The optimum temperature for activity was 55 degrees C and the Ea for catalysis was 39.7 kJ mol-1. An optimum pH for activity of 8.5 was found and the calculated pKE1, pKE2 and pKES1 of enzyme ionisation groups were 6.0, 8.9 and 6.3, respectively. Km values of 22, 50 and 24 microM were calculated for d,l-isocitrate, NADP and Mn2+, respectively, in the Mn2+-dependent reaction and 70, 32 and 159 microM for d,l-isocitrate, NADP and Mg2+, respectively, in the Mg2+-dependent reaction. The decarboxylating activity was inhibited by ATP, ADP and by its reaction products 2-oxoglutarate and NADPH2. Polyclonal antibodies raised against the pure IDH were used to assess the presence of the enzyme in cells subjected to nitrogen starvation.
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PMID:Purification, properties and enhanced expression under nitrogen starvation of the NADP+-isocitrate dehydrogenase from the cyanobacterium Phormidium laminosum. 1020 82


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