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

Glutamine phosphoribosylpyrophosphate amidotransferase is stable in growing cells, but is inactivated in an oxygen-dependent process at various rates in starving or antibiotic-treated cells. On the basis of studies of the purified enzyme, we suggested (D.A. Bernlohr and R.L. Switzer, Biochemistry 20:5675-5681, 1981) that the inactivation in vivo was regulated by substrate stabilization and a competition between stabilizing (AMP) and destabilizing (GMP, GDP, and ADP) nucleotides. This proposal was tested by measuring the intracellular levels of these metabolites under cultural conditions in which the stability of the amidotransferase varied. The results established that the stability of amidotransferase in vivo cannot be explained by the simple interactions observed in vitro. Metabolite levels associated with stability of the enzyme in growing cells did not confer stability under other conditions, such as ammonia starvation or refeeding of glucose-starved cells. The data suggest that a previously unrecognized event, possibly a covalent modification of amidotransferase, is required to mark the enzyme for oxygen-dependent inactivation.
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PMID:Regulation of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase inactivation in vivo. 640 10

The microsomal preparation from the lactating bovine mammary tissue was solubilized by treatment with nonionic detergent, NP-40, at a protein/detergent ratio of 1.5:1 and a detergent concentration of 0.5%. Following centrifugation at 147000 X g for 120 min, the supernatant fraction was incubated with labeled sugar nucleotides, GDP-Man and UDP-GlcNAc. It was found to synthesize a series of lipid-linked saccharides up to (Man)5-(GlcNAc)2. The solubilized glycosyltransferases retained up to about 60% of the activity after two weeks of storage at 4 degrees C. The biosynthesis of glycolipids was stimulated by a mixture of lipids obtained by extracting the mammary microsomes with CHCl3/CH3OH (2:1). A labeled lipid-linked tetrasaccharide of the structure Man alpha 1----3 Man beta----GlcNAc beta----GlcNAc was isolated by labeling baby hamster kidney cells with [2-3H]mannose under conditions of glucose starvation followed by extraction of the cells with CHCl3/CH3OH (2:1) and separation of the lipids by high-performance liquid chromatography. When this lipid-linked tetrasaccharide was incubated with the solubilized bovine mammary microsomes and GDP-Man, it was elongated to a lipid-linked heptasaccharide having the structure Man alpha 1----2Man alpha 1----2Man alpha 1----3(Man alpha 1----6)Man beta----GlcNAc beta----GlcNAc. The kinetics of the elongation reaction also revealed the intermediary formation of smaller amounts of lipid-linked pentasaccharide and hexasaccharide. The elongation reaction did not require any divalent metal ion and had a broad pH optimum between 6.8 and 7.6. The lack of inhibition of the elongation reaction by EDTA or amphomycin support earlier studies that GDP-Man rather than mannosylphosphoryldolichol, is the direct donor of mannosyl residues for the biosynthesis of glycolipids up to (Man)5(GlcNAc)2. Mannosylphosphorylretinol was ineffective as mannosyl donor for the elongation reaction.
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PMID:Solubilization of mannosyltransferase activities for the biosynthesis of mammary glycoproteins. Elongation of tetrasaccharide-lipid to heptasaccharide-lipid by a solubilized enzyme preparation. 669 9

In Escherichia coli, amino acid starvation triggers the rapid synthesis of two guanosine polyphosphates, pppGpp and ppGpp (the 3'-pyrophosphates of GTP and GDP, respectively). Determination of the turnover rate of the ppGpp pool indicated that during serine deprivation, as opposed to other amino acid starvations, the rate of ppGpp degradation is dramatically decreased. This results in a slow but significant accumulation of this regulatory nucleotide in a relA mutant during serine starvation. Similar ppGpp accumulation can be seen during serine starvation in different serine auxotrophic mutants carrying different relA alleles. On the other hand, no ppGpp accumulation is induced in various relaxed strains by serine hydroxamate treatment.
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PMID:Accumulation of ppGpp in a relA mutant of Escherichia coli during amino acid starvation. 676 41

A large amount of pyruvate was excreted into the medium by CP78 (rel+) cells grown on succinate when they were starved for amino acids. In contrast, no such excretion was observed with CP79 (rel-) cells. This phenomenon was also seen with two other isogenic pairs of strains: NF161 (rel+) and NF162 (rel-), and 10B601 (rel+) and 10B602 (rel-). Besides succinate, L-malate, and fumarate were effective carbon sources for the excretion, but glucose, glycerol, and acetate were not. When DL-lactate was used, not only CP78 but also CP79 cells excreted pyruvate. Experiments using [1,4-14C]succinate as a carbon source revealed that pyruvate was formed by decarboxylation of one carboxyl group of succinate and that the pyruvate excretion amounted to about 40% of the total succinate degraded. Experiments designed to elucidate the mechanism of the excretion yielded the following observations. (i) The concentration of pyruvate in CP78 cells grown on the C4-dicarboxylic acids mentioned above was not significantly changed upon amino acid starvation. (ii) Guanosine 5'-diphosphate-3'-diphosphate exerted no effect on the activities of several enzymes thought to be involved in pyruvate-related metabolism. It is suggested firstly that the excretion was not due to some impairment in the biosynthetic pathway of a particular amino acid, but was due to the stringent control of central amphibolic metabolism, and secondly that no de novo protein synthesis was involved in the excretion.
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PMID:Stringent control of intermediary metabolism in Escherichia coli: pyruvate excretion by cells grown on succinate. 704 Mar 57

The ste6 gene of Schizosaccharomyces pombe encodes a putative GDP-GTP exchange factor for the ras1 gene product. Genetic analysis of the ste6 and ras1 genes has shown that they are required for mating and for the response to mating pheromones. In this study we show that expression of the ste6-encoded mRNA is induced by nitrogen starvation, the physiological signal that triggers mating and sexual differentiation. Exposure to mating pheromones enhances the induction of ste6 expression upon nitrogen starvation. Pheromone-induced expression requires not only the function of components of the pheromone-signalling pathway, but also ras1 function. Furthermore, mutants in which the Ras1 protein is activated have higher basal and induced levels of ste6 gene expression than wild-type cells. These observations indicate the existence of a positive-feedback loop through which Ras1 stimulates the expression of its own activator. Since Ste6 is likely to promote the exchange of guanine nucleotides on Ras1 protein, our results suggest an important role for GDP-GTP exchange in the regulation of Ras1 activity during the mating process in S. pombe.
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PMID:Transcriptional regulation of a Ras nucleotide-exchange factor gene by extracellular signals in fission yeast. 770 12

On amino acid starvation, Escherichia coli cells exhibit an adaptive facility termed the stringent response. This is characterized by the production of high levels of a regulatory nucleotide, ppGpp, and concomitant curtailment in rRNA synthesis. Various studies reported earlier indicated that RNA polymerase is the site of action of ppGpp although a direct demonstration of the interaction of ppGpp with E. coli RNA polymerase is still lacking. Here we report the labelling of ppGpp with a fluorescent probe, 1-aminonapthalene-5-sulphonate (AmNS), at the terminal phosphates. AmNS-ppGpp responded much like a ppGpp molecule in an in vitro total transcription assay at selective promoters. Fluorescence titration of the tryptophan emission of RNA polymerase by AmNS-ppGpp indicated a unique binding site in the absence of template DNA. Competition experiments showed that unlabelled ppGpp binds to the enzyme at the same site. Sigma factor seems to have no effect on this binding. The titration profile is also characterized by a single slope in the Scatchard analysis. The presence of GTP or GDP does not influence the binding of AmNS-ppGpp with RNA polymerase. Forster's distance measurement was carried out which placed AmNS-ppGpp 27 A away from the rifampicin-binding domain of RNA polymerase.
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PMID:Evidence for a ppGpp-binding site on Escherichia coli RNA polymerase: proximity relationship with the rifampicin-binding domain. 774 47

Starvation of the yeast Saccharomyces cerevisiae for an amino acid signals increased translation of GCN4, a transcriptional activator of amino acid biosynthetic genes. We have isolated and characterized the GCD6 and GCD7 genes and shown that their products are required to repress GCN4 translation under nonstarvation conditions. We find that both GCD6 and GCD7 show sequence similarities to components of a high-molecular-weight complex (the GCD complex) that appears to be the yeast equivalent of translation initiation factor 2B (eIF-2B), which catalyzes GDP-GTP exchange on eIF-2. Furthermore, we show that GCD6 is 30% identical to the largest subunit of eIF-2B isolated from rabbit reticulocytes. Deletion of either GCD6 or GCD7 is lethal, and nonlethal mutations in these genes increase GCN4 translation in the same fashion described for defects in known subunits of eIF-2 or the GCD complex; derepression of GCN4 is dependent on short open reading frames in the GCN4 mRNA leader and occurs independently of eIF-2 alpha phosphorylation by protein kinase GCN2, which is normally required to stimulate GCN4 translation. Together, our results provide evidence that GCD6 and GCD7 are subunits of eIF-2B in S. cerevisiae and further implicate this GDP-GTP exchange factor in gene-specific translational control.
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PMID:Evidence that GCD6 and GCD7, translational regulators of GCN4, are subunits of the guanine nucleotide exchange factor for eIF-2 in Saccharomyces cerevisiae. 844 23

The development changes in GTP-binding proteins and the regulation of their appearance by calcium ions were investigated during early sexual development in Dictyostelium discoideum. GTP gamma S strongly inhibited gamete cell fusion, while GDP beta S slightly augmented it, suggesting that G-proteins have a critical role in cell fusion. A 52-kDa protein recognized by an anti-GTP-binding site-specific immune serum, was abundant during calcium-dependent early sexual development but decreased in amount concomitant with cell fusion. This protein remained at high levels in Ca(2+)-deficient cultures, suggesting that its down-regulation is linked to the events of sexual development. Analysis of substrates for cholera and pertussis toxin-mediated [32P]ADP-ribosylation in D. discoideum extracts determined that the 52-kDa protein is a G-alpha subunit similar to mammalian Gs. The 52-kDa protein was also detected in vegetative, asexual amoebae, but diminished rapidly within the first 2 h of starvation. Together these data indicate that the 52-kDa protein functions during the growth phase and is lost upon entry into either the sexual or asexual developmental programs. The amounts of several lower molecular weight GTP-binding proteins, ranging from 21- to 28 kDa, increased during the stage of zygote differentiation and their increases were calcium dependent. These data provide the first analysis of G-proteins during sexual development of D. discoideum and lay the foundation for continued analysis of the signal transduction events mediating cell fusion and zygote differentiation.
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PMID:The regulation of GTP-binding proteins during fertilization and zygote differentiation in Dictyostelium discoideum. 848 35

Using the yeast two-hybrid system, we have identified developmentally regulated Dictyostelium genes whose encoded proteins interact with Ras-GTP but not Ras-GDP. By sequence homology and biochemical function, one of these genes encodes a Ras GAP (DdRasGAP1). Cells carrying a DdRasGAP1 gene disruption (ddrasgap1 null cells) have multiple, very distinct growth and developmental defects as elucidated by examining the phenotypes of ddrasgap1 null strains. First, vegetative ddrasgap1 null cells are very large and highly multinucleate cells when grown in suspension, indicating a severe defect in cytokinesis. When suspension-grown cells are plated in growth medium on plastic where they attach and can move, the cells rapidly become mono- and dinucleate by traction-mediated cell fission and continue to grow vegetatively with a number of nuclei (1-2) per cell, similar to wild-type cells. The multinucleate phenotype, combined with results indicating that constitutive expression of activated Ras does not yield highly multinucleate cells and data on Ras null mutants, suggest that Ras may need to cycle between GTP- and GDP-bound states for proper cytokinesis. After starvation, the large null cells undergo rapid fission when they start to move at the onset of aggregation, producing mononucleate cells that form a normal aggregate. Second, ddrasgap1 null cells also have multiple developmental phenotypes that indicate an essential role of DdRasGAP1 in controlling cell patterning. Multicellular development is normal through the mid-slug stage, after which morphological differentiation is very abnormal and no culminant is formed: no stalk cells and very few spores are detected. lacZ reporter studies show that by the mid-finger stage, much of the normal cell-type patterning is lost, indicating that proper DdRasGAP1 function and possibly normal Ras activity are necessary to maintain spatial organization and for induction of prestalk to stalk and prespore to spore cell differentiation. The inability of ddrasgap1 null cells to initiate terminal differentiation and form stalk cells is consistent with a model in which Ras functions as a mediator of inhibitory signals in cell-type differentiation at this stage. Third, DdRasGAP1 and cAMP dependent protein kinase (PKA) interact to control spatial organization within the organism. Overexpression of the PKA catalytic subunit in ddrasgap1 cells yields terminal structures that are multiply branched but lack spores. This suggests that RasGAP and PKA may mediate common pathways that regulate apical tip differentiation and organizer function, which in turn control spatial organization during multicellular development. It also suggests that DdRasGAP1 either lies downstream from PKA in the prespore to spore pathway or in a parallel pathway that is also essential for spore differentiation. Our results indicate that DdRasGAP1 plays an essential role in controlling multiple, potentially novel pathways regulating growth and differentiation in Dictyostelium and suggest a role for Ras in these processes.
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PMID:A Ras GAP is essential for cytokinesis and spatial patterning in Dictyostelium. 905 74

The aim of the present work is to investigate the effect of starvation on brown adipose tissue thermogenic activity with aging. Interscapular brown adipose tissue from female Wistar rats of different ages was used; half of them were fed and the other half were starved for 24 hours. Mitochondria were isolated and mitochondrial protein content, GDP-binding, Cytochrome-c Oxidase activity and uncoupling protein levels were measured. Results show a decrease of all studied parameters, indicating a diminished thermogenic activity with age. The response to starvation is almost the same in all the parameters studied: a general reduction with starvation and a progressive disappearance of this response to starvation with aging. On the whole, these results would indicate a deficient regulation of brown adipose tissue thermogenic activity in old animals, as it happens in other animal models with an alterated thermogenesis.
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PMID:Diminished response to food deprivation of the rat brown adipose tissue mitochondrial uncoupling system with age. 930 33


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