UMLS:C0038187 - FACTA Search

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

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

PhoR of Bacillus subtilis is a histidine sensor-kinase belonging to the family of two-component signal transduction systems. PhoR is responsible for processing the phosphate-starvation signal and providing phosphate input to regulate the level of phosphorylated response regulator, PhoP, which activates/represses Pho regulon gene transcription. The catalytic domain of PhoR is sufficient for the low-phosphate inducible expression of Pho regulon genes since removing the N-terminal membrane-associated domain did not alter the kinetics of Pho induction, albeit the total level of induction was decreased (1). In this study we showed that the complete B. subtilis PhoR protein produced in Escherichia coli can be reverse phosphorylated by PhoP-phosphate. We also used a C-terminal fragment of the PhoR protein, PhoR, to demonstrate that the phosphoryl group on phospho-PhoP was transferred back to PhoR in the reverse phosphorylation reaction or released as inorganic phosphate to the reaction mixture. The reverse phosphorylation of the PhoR protein likely occurs at the same histidine residue (His360) that is utilized for the autokinase reaction by the same protein. In the presence of ADP, the phosphoryl group is further transferred to ADP to form ATP. While the autokinase reaction, the forward phosphotransfer reaction from PhoR approximately P to PhoP, and the release of inorganic phosphate from PhoP approximately P in the presence of PhoR require Mg(2+), the reverse phosphotransfer from PhoP approximately P to PhoR does not. These results indicate that the energy levels of the phosphoryl groups on PhoP and PhoR are very similar. The reversible autokinase reaction and/or the reversible phosphotransfer reaction between PhoR approximately P and PhoP may have a role in PhoP approximately P decay thus influencing the PhoP approximately P concentration in the cell.
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PMID:Decay of activated Bacillus subtilis pho response regulator, PhoP approximately P, involves the PhoR approximately P intermediate. 1043 20

Caenorhabditis elegans uses a variety of attractive olfactory cues to detect food. We show here that the responses to olfactory cues are regulated in a dynamic way by behavioral context and the animal's previous experience. Prolonged exposure to an odorant leads to a decreased response to that odorant, a form of behavioral plasticity called olfactory adaptation. We show that starvation can increase the extent of olfactory adaptation to the odorant benzaldehyde; this effect of starvation persists for several hours after the animals have been returned to food. The effect of starvation is antagonized by exogenous serotonin, which induces many of the same behavioral responses in C. elegans as are induced by food. Starvation also inhibits recovery from adaptation to a different odorant, 2-methylpyrazine, thus enhancing olfactory memory. In addition to its effects on adaptation, starvation modulates olfactory discrimination in C. elegans; starved animals discriminate more classes of odorants than fed animals. Increased olfactory discrimination is also seen in the adaptation-defective mutant adp-1 (ky20). These various forms of behavioral plasticity enhance the ability of starved animals to respond to novel, potentially informative odorants.
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PMID:Environmental signals modulate olfactory acuity, discrimination, and memory in Caenorhabditis elegans. 1045 62

Apoptosis in neuronal tissue is an efficient mechanism which contributes to both normal cell development and pathological cell death. The present study explored the effects of extracellular ATP on starvation-induced apoptosis in rat pheochromocytoma PC12 cells. Incubation of differentiated PC12 cells with ATP for 6h suppressed apoptosis. 2-Methylthio-ATP, a P2 purinoceptor agonist, was as potent as ATP in suppressing apoptosis, whereas adenosine, ADP, alpha,betamethylene-ATP or UTP was totally ineffective. The suppressive action of ATP was dependent upon the presence of extracellular Ca2+ and blocked by co-incubation with the P2 antagonist, suramin. DNA ladder formation, a typical symptom of apoptosis in starved cells, was inhibited by ATP, 2-methylthio-ATP but not by UTP. These results suggest that the inhibitory action of extracellular ATP on apoptotic cell death is mediated via the activation of P2X2 receptors in differentiated PC12 cells.
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PMID:Extracellular ATP inhibits starvation-induced apoptosis via P2X2 receptors in differentiated rat pheochromocytoma PC12 cells. 1080 82

Inorganic polyphosphate (poly P) is a chain of tens or many hundreds of phosphate (Pi) residues linked by high-energy phosphoanhydride bonds. Despite inorganic polyphosphate's ubiquity--found in every cell in nature and likely conserved from prebiotic times--this polymer has been given scant attention. Among the reasons for this neglect of poly P have been the lack of sensitive, definitive, and facile analytical methods to assess its concentration in biological sources and the consequent lack of demonstrably important physiological functions. This review focuses on recent advances made possible by the introduction of novel, enzymatically based assays. The isolation and ready availability of Escherichia coli polyphosphate kinase (PPK) that can convert poly P and ADP to ATP and of a yeast exopolyphosphatase that can hydrolyze poly P to Pi, provide highly specific, sensitive, and facile assays adaptable to a high-throughput format. Beyond the reagents afforded by the use of these enzymes, their genes, when identified, mutated, and overexpressed, have offered insights into the physiological functions of poly P. Most notably, studies in E. coli reveal large accumulations of poly P in cellular responses to deficiencies in an amino acid, Pi, or nitrogen or to the stresses of a nutrient downshift or high salt. The ppk mutant, lacking PPK and thus severely deficient in poly P, also fails to express RpoS (a sigma factor for RNA polymerase), the regulatory protein that governs > or = 50 genes responsible for stationary-phase adaptations to resist starvation, heat and oxidant stresses, UV irradiation, etc. Most dramatically, ppk mutants die after only a few days in stationary phase. The high degree of homology of the PPK sequence in many bacteria, including some of the major pathogenic species (e.g. Mycobacterium tuberculosis, Neisseria meningitidis, Helicobacter pylori, Vibrio cholerae, Salmonella typhimurium, Shigella flexneri, Pseudomonas aeruginosa, Bordetella pertussis, and Yersinia pestis), has prompted the knockout of their ppk gene to determine the dependence of virulence on poly P and the potential of PPK as a target for antimicrobial drugs. In yeast and mammalian cells, exo- and endopolyphosphatases have been identified and isolated, but little is known about the synthesis of poly P or its physiologic functions. Whether microbe or human, all species depend on adaptations in the stationary phase, which is truly a dynamic phase of life. Most research is focused on the early and reproductive phases of organisms, which are rather brief intervals of rapid growth. More attention needs to be given to the extensive period of maturity. Survival of microbial species depends on being able to manage in the stationary phase. In view of the universality and complexity of basic biochemical mechanisms, it would be surprising if some of the variety of poly P functions observed in microorganisms did not apply to aspects of human growth and development, to aging, and to the aberrations of disease. Of theoretical interest regarding poly P is its antiquity in prebiotic evolution, which along with its high energy and phosphate content, make it a plausible precursor to RNA, DNA, and proteins. Practical interest in poly P includes many industrial applications, among which is the microbial removal of Pi in aquatic environments.
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PMID:Inorganic polyphosphate: a molecule of many functions. 1087 45

In the C(4) plant maize (Zea mays L.), two ferredoxin isoproteins, Fd I and Fd II, are expressed specifically in mesophyll and bundle-sheath cells, respectively. cDNAs for these ferredoxins were introduced separately into the cyanobacterium Plectonema boryanum with a disrupted endogenous ferredoxin gene, yielding TM202 and KM2-9 strains expressing Fd I and Fd II. The growth of TM202 was retarded under high light (130 micromol/m(2)/s), whereas KM2-9 grew at a normal rate but exhibited a nitrogen-deficient phenotype. Measurement of photosynthetic O(2) evolution revealed that the reducing power was not efficiently partitioned into nitrogen assimilation in KM2-9. After starvation of the cells in darkness, the P700 oxidation level under far-red illumination increased significantly in TM202. However, it remained low in KM2-9, indicating an active cyclic electron flow. In accordance with this, the cellular ratio of ATP/ADP increased and that of NADPH/NADP(+) decreased in KM2-9 as compared with TM202. These results demonstrated that the two cell type-specific ferredoxins differentially modulate electron flow around photosystem I.
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PMID:Differential electron flow around photosystem I by two C(4)-photosynthetic-cell-specific ferredoxins. 1101 7

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