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

Aspartate transcarbamylase is synthesized during exponential growth of Bacillus subtilis and is inactivated when the cells enter the stationary phase. This work is a study of the regulation of aspartate transcarbamylase synthesis during growth and the stationary phase. Using specific immunoprecipitation of aspartate transcarbamylase from extracts of cells pulse-labeled with tritiated leucine, we showed that the synthesis of the enzyme decreased very rapidly at the end of exponential growth and was barely detectable during inactivation of the enzyme. Synthesis of most cell proteins continued during this time. When the cells ceased growing because of pyrimidine starvation of a uracil auxotroph, however, synthesis and inactivation occurred simultaneously. Measurement of pools of pyrimidine nucleotides and guanosine tetra- and pentaphosphate demonstrated that failure to synthesize aspartate transcarbamylase in the stationary phase was not explained by simple repression by these compounds. The cessation of aspartate transcarbamylase synthesis may reflect the shutting off of a "vegetative gene" as part of the program of differential gene expression during sporulation. However, aspartate transcarbamylase synthesis decreased normally at the end of exponential growth at the nonpermissive temperature in a mutant strain that is temperature-sensitive in sporulation and RNA polymerase function. Cessation of aspartate transcarbamylase synthesis appeared to be normal in three other temperature-sensitive RNA polymerase mutants and in several classes of spo0 mutants.
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PMID:Aspartate transcarbamylase synthesis ceases prior to inactivation of the enzyme in Bacillus subtilis. 9 40

Repression of biosynthetic enzyme synthesis in Pseudomonas putida is incomplete even when the bacteria are growing in a nutritionally complex environment. The synthesis of four of the enzymes of the arginine biosynthetic pathway (N-acetyl-alpha-glutamokinase/N-acetylglutamate-gamma-semialdehyde dehydrogenase, ornithine carbamoyltransferase and acetylornithine-delta-transaminase) could be repressed and derepressed, but the maximum difference observed between repressed and derepressed levels for any enzyme of the pathway was only 5-fold (for ornithine carbamoyltransferase). No repression of five enzymes of the pyrimidine biosynthetic pathway (aspartate carbamoyltransferase, dihydro-orotase, dihydro-orotate dehydrogenase, orotidine-5'-phosphate pyrophosphorylase and orotidine-5'-phosphate decarboxylase) could be detected on addition of pyrimidines to minimal asparagine cultures of P. putida A90, but a 1-5- to 2-fold degree of derepression was found following pyrimidine starvation of pyrimidine auxotrophic mutants of P. putida A90. Aspartate carbamoyltransferase in crude extracts of P. putida A90 was inhibited in vitro by (in order of efficiency) pyrophosphate, CTP, UTP and ATP, at limiting but not at saturating concentrations of carbamoyl phosphate.
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PMID:Regulation of arginine and pyrimidine biosynthesis in Pseudomonas putida. 17 12

Culturing of Salmonella typhimurium or Escherichia coli cells in the presence of low concentrations (</=1 mug/ml) of chloramphenicol (CAP) permitted exponential growth, but at doubling times up to twice those of controls. When such cultures were subsequently starved for uracil or arginine, derepression of aspartate transcarbamylase (ATCase) or ornithine transcarbamylase, respectively, was enhanced three- to 10-fold as compared to cultures not exposed to CAP. Enhancement of beta-galactosidase synthesis by prior exposure to CAP was also observed in uracil-starved E. coli cultures. Stimulation of enzyme synthesis appeared to be a specific effect of CAP; low levels of erythromycin, puromycin, sparsomycin, tetracycline, and rifampin did not show such effects. Derepression of ATCase synthesis in exponentially growing cells in the presence of CAP did not result in stimulation of enzyme synthesis by CAP. A prior history of growth of a culture in the presence of CAP was shown to be necessary for enhancement of enzyme synthesis by CAP; furthermore, continued presence of CAP in the medium during starvation was not necessary for enhanced enzyme synthesis and inhibited it in some instances. Enhanced enzyme synthesis in starving, CAP-treated cultures could be blocked by rifampin, which suggested that CAP treatment allows prolonged or more extensive messenger ribonucleic acid synthesis.
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PMID:Stimulation of derepressed enzyme synthesis in bacteria by growth on sublethal concentrations of chloramphenicol. 114 88

Aspartokinase II from Bacillus subtilis was shown by immunochemical methods to be regulated by degradation in response to starvation of cells for various nutrients. Ammonium starvation induced the fastest aspartokinase II decline (t1/2 = 65 min), followed by amino acid starvation (t1/2 = 80 min) and glucose limitation (t1/2 = 120 min). Loss of enzyme activity was closely correlated with the disappearance of the alpha subunit; degradation of the beta subunit was somewhat delayed or slower under some conditions. Pulse-chase experiments demonstrated that aspartokinase II was stable during exponential growth; the synthesis of the enzyme rapidly declined in response to nutrient exhaustion. The degradation of aspartokinase II was interrupted by inhibitors of energy production and protein synthesis but was not changed in a mutant lacking a major intracellular protease. Mutants lacking a normal stringent response displayed only a slight decrease in the rate of aspartokinase II degradation, even though aspartate transcarbamylase was degraded more slowly in the same mutant cells. These results indicate that although energy-dependent degradation of biosynthetic enzymes is a general phenomenon in nutrient-starved B. subtilis cells, the degradation of specific enzymes probably involves different pathways.
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PMID:Aspartokinase II from Bacillus subtilis is degraded in response to nutrient limitation. 216 95

The enzymes in the pathway for de novo pyrimidine biosynthesis, including those associated with the tri-functional CAD protein, show a marked increase in activity in rapidly growing cells and tissues. To learn more about the relationship of this pathway to cellular proliferation, we have studied changes in levels of CAD RNA, rates of CAD protein synthesis, and levels of aspartate transcarbamylase activity in Syrian hamster ts13 cells in response to serum starvation and serum stimulation. The steady-state level of CAD RNA and the synthetic rate of CAD protein decrease by 12- to 15-fold following 24 hr of serum starvation, as compared to exponentially growing cells. Upon serum stimulation of quiescent cells, steady-state CAD RNA levels increase substantially (13-fold), peaking during mid to late G1. Parallel increases occur in the synthesis of new CAD protein and in aspartate transcarbamylase activity. At the same time, the rate of CAD transcription increases only about twofold. These findings indicate that regulation of CAD expression in this system is primarily at the post-transcriptional level. This is in contrast to the transcriptional regulation of CAD previously reported in terminally differentiating HL60 cells (Rao et al., Mol. Cell. Biol. 7, 1961-1966, 1987). While both systems indicate that CAD gene expression is dependent on cell growth, there apparently are alternative mechanisms that can produce the same effect. Evidence is also presented that indicates that the accumulation of CAD transcripts during serum stimulation requires the synthesis of new proteins.
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PMID:CAD gene expression in serum-starved and serum-stimulated hamster cells. 246 83

The arginine-independent, de novo biosynthetic pathway of pyrimidines in Dictyostelium discoideum is initiated by a class II carbamoyl-phosphate synthetase (EC 6.3.5.5) specific for pyrimidine biosynthesis which utilized L-glutamine as its N donor and was partially inhibited by both UTP and CTP. The second step in the de novo pathway was provided by an unregulated aspartate transcarbamoylase (EC 2.1.3.2) which primarily appeared as a multimeric enzyme of 105 kilodaltons. The next enzyme, dihydroorotase (EC 3.5.2.3), was approximately 90-100 kilodaltons. Although the early enzymatic activities of the pyrimidine pathway appeared to reside in independent protein complexes, various unstable molecular species were observed. These structural variants may represent proteolytic fragments of a multienzyme complex. In addition to de novo synthesis, the amoeba demonstrated the capacity for salvage utilization of uracil, uridine, and cytidine. Upon starvation on a solid substratum, axenically grown amoebas began a concerted developmental program accompanied by a restructuring of nucleotide metabolism. The absolute levels of the ribonucleotide pools droppedby 98% within 30 h; however, both the adenylate energy charge and the GTP/ATP ratios were maintained for 50 h after the initiation of development. The maintenance of these metabolic energy parameters required the tight cell-cell contact necessary for development, and the capacity for pyrimidine metabolism was maintained throughout developmental morphogenesis.
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PMID:Characterization of pyrimidine metabolism in the cellular slime mold, Dictyostelium discoideum. 256 62

This study describes the isolation and characterization of a mutant (strain GP122) of Salmonella typhimurium with a partial deficiency of phosphoribosylpyrophosphate (PRPP) synthetase activity. This strain was isolated in a purE deoD gpt purin auxotroph by a procedure designed to select guanosine-utilizing mutants. Strain GP122 had roughly 15% of the PRPP synthetase activity and 25% of the PRPP pool of its parent strain. The mutant exhibited many of the predicted consequences of a decreased PRPP pool and a defective PRPP synthetase enzyme, including: poor growth on purine bases; decreased accumulation of 5-aminoimidazole ribonucleotide (the substrate of the blocked purE reaction) under conditions of purine starvation; excretion of anthranilic acid when grown in medium lacking tryptophan; increased resistance to inhibition by 5-fluorouracil; derepressed levels of aspartate transcarbamylase and orotate phosphoribosyltransferase, enzymes involved in the pyrimidine de novo biosynthetic pathway; growth stimulation by PRPP-sparing compounds (e.g. guanosine, histidine); poor growth in low phosphate medium; and increased heat lability of the defective enzyme. This mutant strain also had increased levels of guanosine 5'-monophosphate reductase. This genetic lesion, designated prs, was mapped by conjugation and phage P22-mediated transduction at 35 units on the Salmonella linkage map.
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PMID:Characterization of a Salmonella typhimurium mutant defective in phosphoribosylpyrophosphate synthetase. 258 45

The catalytic and regulatory polypeptide chains of Escherichia coli aspartate transcarbamoylase are encoded by the pyrB and pyrI genes, respectively, which constitute a single transcriptional unit in the pyrBI operon. The DNA sequence immediately preceding the first structural gene, pyrB, contains a short open reading frame that could encode a 44-amino acid leader peptide and a (G+C)-rich region of dyad symmetry followed by eight thymidine residues. Synthesis of the enzyme is negatively controlled at the level of transcription depending on the cellular level of UTP, and an attenuation mechanism has been proposed to account for the 70-fold increase in pyrBI expression on pyrimidine starvation. The potential role of the dyad and eight thymidines as an attenuator was tested with a plasmid containing the promoter region of the pyrBI operon upstream of the galK coding sequence. When cells containing this plasmid, pPYRB10, were grown in a medium low in uracil, there was an 83-fold increase in galactokinase activity compared with the same cells grown at high uracil levels. This regulation is similar to that for aspartate transcarbamoylase synthesis in cells depleted of pyrimidines. Deletions constructed in the promoter region of pPYRB10 from the 3' side produced one plasmid that retained normal control of galK expression and five that exhibited greatly reduced regulation. Nucleotide sequence determination showed that the one deletion mutation that was functionally similar to the wild-type plasmid contained the entire region of dyad symmetry, including the eight thymidines. The plasmids with more extensive deletions lacked the region with dyad symmetry and the eight thymidines. One of the deletion mutants that exhibited very low levels of regulation lacks the entire sequence coding for the putative leader peptide up to the major promoter. The results demonstrating the crucial role of a 19-nucleotide sequence (from -33 to -15) support an attenuation model but indicate that other mechanisms also contribute to the regulation of the pyrBI operon.
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PMID:Regulation of aspartate transcarbamoylase synthesis in Escherichia coli: analysis of deletion mutations in the promoter region of the pyrBI operon. 299 85

Aspartate transcarbamoylase labeled with 3-fluorotyrosine was purified from an Escherichia coli strain which was auxotrophic for tyrosine and overproduced aspartate transcarbamoylase upon uracil starvation. The labeled enzyme in which about 85% of the tyrosines were replaced by fluorotyrosine exhibited high enzyme activity that varied in a sigmoidal manner with respect to the aspartate concentration. Also, the labeled enzyme was inhibited by CTP, activated by ATP, and exhibited a 2.6% decrease in sedimentation coefficient upon the addition of the active-site ligand, N-(phosphonacetyl)-L-aspartate. Thus, despite extensive replacement of tyrosines by fluorotyrosine, the modified enzyme was similar to native aspartate transcarbamoylase. The 19F nuclear magnetic resonance spectrum of isolated regulatory subunits labeled with fluorotyrosine consisted of a single peak. Addition of the activator, ATP, or the inhibitor, CTP, caused a loss of intensity at about 61.3 ppm upfield from a trifluoroacetic acid reference and an increase at about 61.5 ppm, but CTP also caused an increase at about 61.0 ppm. Five overlapping resonances were observed in the 19F NMR spectrum of unliganded catalytic subunits containing fluorotyrosine. Although the binding of the bisubstrate analog, N-(phosphonacetyl)-L-aspartate, or the combination of carbamoylphosphate and succinate caused similar disappearances of resonances, the addition of N-(phosphonacetyl)-L-aspartate caused the appearance of resonances not observed with carbamoylphosphate plus succinate. Carbamoylphosphate alone perturbed three or four resonances and the subsequent addition of succinate affected at least two.
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PMID:19F nuclear magnetic resonance studies of fluorotyrosine-labeled aspartate transcarbamoylase. Properties of the enzyme and its catalytic and regulatory subunits. 404 74

The aspartic transcarbamylase (ATCase) activity of Bacillus subtilis cells disappears rapidly from stationary-phase cells prior to sporulation. ATCase activity does not appear in the culture fluid during the stationary phase; hence the enzyme appears to be inactivated in the cells. The enzyme is inactivated normally in two different mutants lacking proteases; the activity is very stable in crude extracts of cells or in the culture fluid. These results suggest that ATCase is not inactivated by the general proteolysis that occurs in sporulating bacteria. The inactivation of ATCase can be completely inhibited after it has begun by oxygen starvation or addition of fluoroacetate. Inhibitors of oxidative phosphorylation and electron transport also interrupt the inactivation of ATCase. The inactivation of ATCase is very slow in two mutant strains that are deficient in enzymes of tricarboxylic acid cycle. Addition of gluconate to stationary cultures of the mutant strains, which is known to restore depleted adenosine 5'-triphosphate pools in these bacteria, also restores inactivation of ATCase. These experiments support the conclusion that the generation of metabolic energy is necessary for the inactivation of ATCase in stationary cells. ATCase activity is stable in growing cells in which ATCase synthesis is repressed by addition of uracil; the enzyme is inactivated normally, however, when such cells cease growing.
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PMID:Inactivation of aspartic transcarbamylase in sporulating Bacillus subtilis: demonstration of a requirement for metabolic energy. 419 42


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