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

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

The ribonucleoside triphosphate, deoxyribonucleoside triphosphate, 3' -diphosphate guanosine 5' -diphosphate (ppGpp), and 5-phosphoribosyl 1-pyrophosphate (PRPP) pools in Escherichia coli B were determined by thin-layer chromatography during changing conditions to ammonium starvation. The intracellular concentrations of all nucleotides were found to change in a well-defined order several minutes before andy observed change in the optical density of the culture. The levels of purine nucleoside triphosphates (adenosine 5' -triphosphate [CTP], dCTP) and uridine nucleotides (uridine 5' -triphosphate, deoxythymidine 5'-triphosphate). The deoxyribonucleotides thus behaved as the ribonucleotides. The levels of ppGpp increased 11-fold after the decrease in uridine nucleotides, when the accumulation of stable ribonucleic acid (RNA) stopped. The level of the nucleotide pool did not stabilize until 30 min after the change in optical density. The pool of dGTP dropped concomitantly with the pool of CTP. The nucleotide precursor PRPP exhibited a transient increase, wtih maximum value of four times the exponential levels at the onset of starvation. Apparently the cell adjusts early to starvation by reducing either the phosphorylating activity or the nucleotide biosynthetic activity. As in other downshift systems, the accumulation of stable RNA stopped before the break in optical density and before the stop in protein accumulation. Cell divisions were quite insensitive to the control mechanisms operating on RNA and protein accumulation under ammonium starvation, since the cells continued to divide for 21 min without any net accumulation of RNA.
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PMID:Regulation of PRPP and nucleoside tri and tetraphosphate pools in Escherichia coli under conditions of nitrogen starvation. 32 22

A thermosensitive conditional yeast mutant (ts-187) which suppresses protein synthesis at the nonpermissive temperature (36 degrees C) also suppresses RNA synthesis. The effect of temperature on the mutant is similar to the addition of cycloheximide--it inhibits the incorporation of labeled precursors into RNA in both whole cells and isolated nuclei. The effect of temperature is selective for the RNA polymerases bound to the nuclear template but not for the total RNA polymerases. Thus, the specific activities and total amounts of RNA polymerase species extracted and assayed with exogenous DNA template are similar in the ts-187 cultured at 23 degrees C and at 36 degrees C. On the contrary, the nuclear polymerases, i.e., RNA synthesis in isolated nuclei, are dramatically inhibited in cells cultured at 36 degrees C. When amino acid starved ts-187 cells are transferred to 36 degrees C, release from the inhibtion of RNA synthesis is observed. As with the addition of cycloheximide, this relaxation is observed in cells but not in isolated nuclei. The parental strain, A364A, which responds by stimulating instead of inhibiting protein synthesis when the temperature is increased to 36 degrees C, also exhibits an inhibition in the incorporation of labeled precursor into RNA as well as reducing RNA synthesis in isolated nuclei. However, these are transitory inhibitions and afterward there is reinitiation of both processes. Reinitiation of RNA synthesis in isolated nuclei is similar to the relaxed phenomenon and it is called "nuclear relaxation". This relaxation can only be obtained if protein synthesis is not inhibited; however, cellular relaxation occurs in the absence of protein synthesis. The repression of the nuclear RNA polymerase activities which starvation and inhibition of protein synthesis produce appears to be due to a restriction in the nuclear DNA template. This notion is supported by the fact that a net diminution of these nuclear enzyme activities is observed in spheroplasts cultured under starving conditions. Studies of the four main ribonucleotide pools indicate that stringency and inhibition of protein synthesis (ts-187 cultured at 36 degrees C) produce an increase in UTP and CTP pools. This is consistent with the concept that stringency and inhibition of protein synthesis affect the rate of utilization rather than the synthesis of these ribonucleotide residues. In the A364A and ts-187 yeast strains, the conversion of uracil but not of uridine into the UTP and CTP is inhibited when there is inhibition of the nuclear RNA polymerases. This indicates that the uracil phosphoribosyltransferase but not the uridine-cytidine kinase is allosterically inhibited by UTP and CTP in yeast. The feedback inhibition in the metabolic pathway of the base explains why relaxation cannot be detected when uracil instead of uridine is used as the labeled RNA precursor.
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PMID:Control of ribonucleic acid synthesis in eukaryotes. 2. The effect of protein synthesis on the activities of nuclear and total DNA-dependent RNA polymerase in yeast. 77 13

Sulfur-deficient tRNA, isolated from Escherichia coli HfrC, rel-, met-, cys-, lambda, after cysteine starvation, was found to have an increased acceptance of isoleucine in proportion to the deficiency of 4-thiouridine. Isoleucine acceptance was not altered in the presence of other amino acids of CTP, and the higher acceptance was observed over a wide range of magnesium, isoleucine, tRNA and enzyme concentrations. The Vmax value for sulfur-deficient tRNA was more than three times greater than observed for normal tRNA. Methylated albumin kieselguhr (MAK) chromatography revealed three isoacceptor peak for normal tRNA, while sulfur-deficient tRNA was missing tRNAile, and exhibited a larger, shifted peaks for tRNA normal tRNA, while sulfur-deficient tRNA was missing tRNAille 2, and exhibited a large shifted peak for tRNAile 3 . Treatment with crude RNA sulfurtransferase both lowered the isoleucine acceptance for sulfur-deficient tRNA to that seen for normal tRNA, and restored the missing isoacceptor on MAK. The possibility that thionucleotides may play a role in the aminoacylation of tRNAile in E. coli is discussed.
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PMID:Increased isoleucine acceptance by sulfur-deficient transfer RNA from Escherichia coli. 78 31

(6R)-5,10-Dideaza-5,6,7,8-tetrahydrofolic acid [(6R)DDATHF] is a folate antimetabolite with activity specifically directed against de novo purine synthesis, primarily through inhibition of glycinamide ribonucleotide transformylase. This inhibition resulted in major changes in the size of the nucleotide pools in CCRF-CEM cells. After a 4-h incubation with 1 microM (6R)DDATHF, dramatic reductions in the ATP and GTP pools were observed, with almost no effect on CTP, UTP, and deoxyribonucleotide pools. When the incubation was continued in drug-free medium, recovery of ATP and GTP pools was protracted. ATP did not return to normal until 24-36 h, and GTP pools were only partially repleted by 48 h. The ATP and GTP pools were not affected when the initial 4-h incubation with (6R)DDATHF was conducted in the presence of 100 microM hypoxanthine. Addition of hypoxanthine to the medium after a 4-h incubation with (6R)DDATHF caused rapid recovery of the ATP and GTP pools. Similar effects were seen when the purine precursor aminoimidazole carboxamide was used in place of hypoxanthine. The effect of (6R)DDATHF on nucleotide pools and the capability of hypoxanthine or aminoimidazole carboxamide to prevent or reverse this phenomenon correlated directly with the inhibition of cell growth. Presumably as a consequence of the decrease in purine nucleotide triphosphate levels, the conversion of exogenously added uridine, thymidine, and deoxyuridine to nucleotides was markedly decreased. These effects were protracted for almost 48 h and were also reversed by hypoxanthine. Differential repletion of ATP and GTP pools after (6R)DDATHF pre-treatment demonstrated that diminished precursor phosphorylation is primarily a consequence of GTP rather than ATP starvation.
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PMID:(6R)-5,10-Dideaza-5,6,7,8-tetrahydrofolic acid effects on nucleotide metabolism in CCRF-CEM human T-lymphoblast leukemia cells. 170 49

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

We have characterized a digitonin-permeabilized cell system for the ATP-dependent degradation of endogenous long-lived proteins. Proteolysis requires Mg2+ and ATP hydrolysis. Other nucleotide triphosphates (CTP, UTP) can partially replace the ATP requirement. The enhanced rate of degradation of long-lived proteins in response to serum starvation is maintained in the permeabilized cell system and can be partially inhibited by lysosomal inhibitors. The maintenance of intracellular architecture and ease of manipulation of soluble components make the permeabilized cell system ideal for studying the proteolysis of both endogenous and exogenous substrates.
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PMID:An ATP-dependent system specific for degradation of long-lived proteins in permeabilized cells. 334 14

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

1. Nuclei from rat liver incubated with S-adenosyl[methyl-(14)C]methionine incorporated radioactivity into RNA and into lipid and protein. 2. All of the labelled RNA was extracted from the nuclei with trichloroacetic acid at 90 degrees C. 3. The [(14)C]methyl-group incorporation into the hot-trichloroacetic acid extract was 30% inhibited by the addition of actinomycin D (100mug/mg of DNA) or by the omission of CTP, GTP and UTP. 4. Assuming that the main substrate for this triphosphate-dependent methylation was newly synthesized precursor rRNA containing one methyl group/30 uridylate residues, it was calculated that approx. 60% of the [(14)C]UMP incorporated under similar conditions represented precursor rRNA synthesis. 5. In agreement with this, low concentrations of actinomycin D (approx. 1mug/mg of DNA) sufficient to abolish the triphosphate-dependent incorporation of [(14)C]methyl group inhibited 68% of the [(14)C]UMP incorporation. 6. The incorporation of [(14)C]UMP by nuclei from starved animals decreased progressively with increasing periods of starvation, whereas the triphosphate-dependent [(14)C]methyl-group incorporation was not further decreased after 1 day of starvation. 7. This suggests that precursor rRNA synthesis decreased within 1 day whereas other species of RNA were affected only after longer periods of starvation.
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PMID:Methylation of newly synthesized ribonucleic acid by isolated rat liver nuclei. Characterization of the ribonucleic acid synthesized by nuclei from starved animals. 512 82

Aminoimidazole carboxamide ribonucleoside (AIC-R), a purine precursor, has biphasic effects on the growth of Chinese hamster fibroblasts. At 200 microM AIC-R cell growth is almost completely arrested, while at 50 and 700 microM AIC-R cell growth is comparable to that observed in the absence of nucleoside. The growth inhibition produced by AIC-R is the consequence of inhibition of the orotate phosphoribosyltransferase-orotidylic decarboxylase (OPRT-ODC) reactions, as evidenced by a 87% reduction in the intracellular concentrations of UTP and CTP, accumulation of orotate in the medium, and restoration of normal growth by inclusion of 100 microM uridine in the medium. Inhibition of pyrimidine nucleotide synthesis at 200 microM AIC-R is associated with an 82% reduction in the intracellular concentration of PP-ribose-P and a 150% increase in the concentration of purine nucleotides. Restoration of cell growth to a normal rate at 700 microM AIC-R--a condition under which PP-ribose-P remains depressed and purine nucleotide concentrations are also depressed (40% of control)--and absence of toxicity at 50 microM AIC-R--a condition under which purine nucleotide concentrations are increased by 150% and PP-ribose-P concentration is normal--suggest that the inhibition of OPRT-ODC observed at 200 microM AIC-R is caused by the combination of the reduction in PP-ribose-P and increase in purine nucleotides. These studies provide a better understanding of the control of the OPRT-ODC reactions in the cell and provide additional insight into the basis of pyrimidine starvation induced by purine nucleosides.
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PMID:Aminoimidazole carboxamide ribonucleoside toxicity: a model for study of pyrimidine starvation. 616 28


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