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

Uracil phosphoribosyltransferase from Escherichia coli K12 was purified to homogeneity as determined by polyacrylamide gel electrophoresis. For this purpose a pyrimidine-requiring strain harboring the upp gene on a ColE1 plasmid was used, which showed 15-times higher uracil phosphoribosyltransferase activity in a crude extract. When this strain was grown under conditions of uracil starvation, an additional 10-times elevation of the enzyme activity was obtained. The molecular weight of uracil phosphoribosyltransferase was determined to be 75000; the enzyme consists of three subunits with a molecular weight of 23500. Uracil phosphoribosyltransferase is specific for uracil and some uracil analogues. The apparent Km values for uracil and PRib-PP were 7 microM and 300 microM, respectively. As an effector of enzyme activity, GTP lowered the Km for PRib-PP to 90 microM and increased the Vmax value 2-fold, but had no effect on the Km for uracil. The effect of GTP was found to be pH-dependent. The enzymatic characterization of uracil phosphoribosyltransferase and the observed regulation of its synthesis emphasizes the role of the enzyme in pyrimidine salvage.
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PMID:Purification and some properties of uracil phosphoribosyltransferase from Escherichia coli K12. 351 46

Complexes of elongation factor Tu (EF-Tu) with guanosine 3'-diphosphate 5'-diphosphate (ppGpp) bind to ribosomes where they slow the incorporation of aminoacyl-tRNAs into protein by inhibiting both the binding of aminoacyl-tRNA.EF-Tu.GTP ternary complexes and the formation of peptide bonds. The latter action increases the time available for aminoacyl-tRNA rejection by the ribosome and, therefore, increases the effectiveness of proofreading. Synthesis of ppGpp and the formation of EF-Tu.ppGpp occur in vivo in response to amino acid starvation. Our finding, therefore, suggests an explanation for the otherwise puzzling observation that amino acid starvation has, at most, a moderate effect on the fidelity of protein synthesis in wild-type Escherichia coli. We suggest that an EF-Tu.ppGpp-induced increase in the effectiveness of proofreading buffers the overall translational fidelity of these cells against amino acid starvation-induced errors in initial selection of aminoacyl-tRNA ternary complexes.
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PMID:Elongation factor Tu.guanosine 3'-diphosphate 5'-diphosphate complex increases the fidelity of proofreading in protein biosynthesis: mechanism for reducing translational errors introduced by amino acid starvation. 351 44

We have investigated the physiological conditions under which meiosis and the ensuing sporulation of Saccharomyces cerevisiae are initiated. Initiation of sporulation occurs in response to carbon, nitrogen, phosphorus, or sulfur deprivation, and also, when met auxotrophs are partially starved for methionine, but not after starvation of other amino acid auxotrophs. It also occurs after partial starvation of pur or gua auxotrophs for guanine but not after starvation of ura auxotrophs for uracil. Under all these sporulation conditions the concentrations of both guanine nucleotides (GTP) and S-adenosylmethionine (SAM) decrease whereas those of other nucleotides show no trend. We show that the decrease of guanine nucleotides is essential for the initiation of meiosis and sporulation: when a gua auxotroph, also lacking one of the two SAM synthetases, is starved for guanine but supplemented with 0.1 mM methionine, GTP decreases while SAM slightly increases and yet the cells sporulate.
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PMID:Partial deprivation of GTP initiates meiosis and sporulation in Saccharomyces cerevisiae. 390 31

A class of arabinosyladenine-resistant baby hamster kidney (BHK) cell mutants, isolated in our laboratory, shows cross-resistance to deoxyadenosine, alteration of adenosine kinase, elevation of spontaneous mutation rate, and extreme sensitivity to adenosine. One of these adenosine sensitive mutants, ara-s10d, was isolated spontaneously and studies with Ador revertants suggest the involvement of a single pleiotropic mutation. The enhanced adenosine toxicity in ara-s10d cells can be attributed to pyrimidine nucleotide starvation and to at least one other mechanism, which is associated with a 200-fold elevation of IMP, 3-5 fold elevation of ATP, GTP, S-adenosylmethionine (AdoMet) and methylthioadenosine (MeSAdo).
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PMID:Multiple mechanisms of adenosine toxicity in an adenosine sensitive mutant of baby hamster kidney (BHK) cells. 399 28

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

Lack of three different amino acids or treatment with the analogue DL-serine hydroxamate does not induce the accumulation of ppGpp and pppGpp, the 3'-pyrophosphates of GDP and GTP, respectively, in Rhizobium meliloti strain 41. Surprisingly, RNA accumulation is controlled under the above mentioned conditions stringently. Moreover, no significant RNA accumulation was found during chloramphenicol, tetracycline, and streptomycin treatment, suggesting that R. meliloti, unlike any other bacteria in investigated so far, is not able to accumulate RNA without ongoing protein synthesis. On the other hand, lack of carbon source and ammonium starvation result in a significant ppGpp accumulation.
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PMID:Absence of accumulation of ppGpp and RNA during amino acid starvation in Rhizobium meliloti. 617 41

In Escherichia coli, the physiological conditions governing the expression of an acid phosphatase with an optimum pH of 2.5 were determined. By contrast with most enzymes, the synthesis of this phosphatase was turned off in exponentially growing bacteria and started as soon as cultures entered the stationary phase. A starvation for inorganic phosphate resulted in a premature full induction, while carbon, nitrogen, and sulfur limitations were inefficient. In the presence of nonlimiting amounts of inorganic phosphate, however, the transfer of the culture to anaerobic conditions led to an immediate accumulation of the acid phosphatase. Cyclic AMP exerted a strong negative control on the biosynthesis and of this enzyme for which the integrity of both the cya and the crp gene functions was necessary. The acid phosphatase was purified to apparent homogeneity and behaved as a monomeric protein with a molecular weight of about 45,000. It had predominantly a phosphoanhydride phosphatase activity and preferentially hydrolyzed the gamma-phosphoryl residue of GTP (Km = 0.35 mM) and the 5'-beta-phosphoryl residue of ppGpp (Km = 1.8 mM). The corresponding beta-phosphoryl residue of GDP was little hydrolyzed, while CTP, ATP, and UTP were not. The enzyme did not split most phosphomonoesters with the exception of the synthetic substrate p-nitrophenyl phosphate (Km = 2.7 mM), 2,3-bisphosphoglycerate (Km = 5 mM), and fructose 1,6-bisphosphate (Km = 5 mM). It was competitively inhibited by tartaric acid and by sodium fluoride (Ki = 60 microM). In addition, it was sensitive to the inhibitor of the translation elongation factor EF-G fusidic acid, and was also strongly inhibited by the triazine dye Cibacron Blue F3GA (Ki = 0.3 microM), suggesting the existence of a site able to recognize nucleotides.
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PMID:The acid phosphatase with optimum pH of 2.5 of Escherichia coli. Physiological and Biochemical study. 628 21

Most beta-adrenergic effects are mediated by activation of the enzyme adenylate cyclase. Hormone binds to the receptor leading to an accelarated binding of GTP to the coupling protein, the N-protein, which is activated. This causes an activation of the adenylate cyclase and an increased formation of cAMP, the intracellular second messenger. The same principles hold good for other hormones coupled to adenylate cyclase. The sensitivity of the adenylate cyclase may be altered in different clinical and experimental conditions. An increased sensitivity is seen in hyperthyroidism in man and in the rat, and during starvation in rats. A decreased sensitivity is seen in hypothyroidism, in patients with pheochromocytoma, pseudohypoparathyroidism type I or multiple symmetric lipomatosis. Several reasons for the altered sensitivity have been suggested. The number of hormone receptors, the coupling between receptor and N-protein, the amount or function of the N-protein or the PDE activity may all vary in different conditions.
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PMID:Coupling between the beta-adrenergic receptor and the adenylate cyclase--pathophysiological implications. 631 52

The interaction of the Escherichia coli elongation factor Tu guanosine tetraphosphate complex (EF-Tu ppGpp) with aminoacyl-tRNAs(aa-tRNA) was reinvestigated by gel filtration and hydrolysis protection experiments. These experiments show that EF-Tu X ppGpp like EF-Tu X GDP (Pingoud, A., Block, W., Wittinghofer, A., Wolf, H. & Fischer, E. (1982) J. Biol. Chem. 257, 11261-11267) forms a fairly stable complex with Phe-tRNAPhe, KAss being 0.6 X 10(5) M-1 at 25 degrees C. The binding of the EF-Tu X ppGpp X aa-tRNA complex to programmed ribosomes was investigated by a centrifugation technique. It is shown that this complex is bound codon-specific with KAss = 3 X 10(7) M-1 at 0 degrees C and that it stimulates peptidyl transfer. A numerical estimation of the intracellular concentration of EF-Tu X GTP X aa-tRNA and EF-Tu X ppGpp X aa-tRNA during normal growth and under the stringent response indicates that ppGpp accumulation does affect the EF-Tu X GTP X aa-tRNA concentration but does not lead to major depletion of this pool. Furthermore, due to the higher affinity of EF-Tu X GTP to aa-tRNA and of the ternary complex EF-Tu X GTP X aa-tRNA to the ribosome, EF-Tu X ppGpp X aa-tRNA binding to the ribosome is not significant. According to our measurements and calculations, therefore, a direct participation of EF-Tu in slowing down the rate of protein biosynthesis and improving its accuracy during amino acid starvation is not obvious.
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PMID:The elongation factor Tu from Escherichia coli, aminoacyl-tRNA, and guanosine tetraphosphate form a ternary complex which is bound by programmed ribosomes. 635 17

The inhibition of elongation factors G, Tu and Ts by ppGpp was studied in vitro in a translation system with missense frequency and elongation rate similar to those in vivo. ppGpp inhibits EF-G with KI = 6 X 10(-5) M. When ppGpp is in twofold excess over GTP and EF-G is the rate-limiting component, the elongation rate is reduced twofold by ppGpp. EF-Tu is inhibited with KI = 7 X 10(-7) M in the absence of EF-Ts. When EF-Ts is added, the binding of ppGpp to EF-Tu becomes successively weaker. 1/KI depends linearly on 1/[Ts] and the intercept at the abscissa gives KI = 4 X 10(-5) M. This reflects the binding of ppGpp to the binary TuTs complex. The slope reveals that the binding of EF-Ts to the TuMS binary complex is strong (10(-6) M). ppGpp may thus inhibit the cycling of EF-Tu indirectly by the removal of the free EF-Ts by its adsorption to TuMS, as well as directly by simple binding to Tu. EF-Tu inhibition by ppGpp can be fully reversed by high levels of aminoacyl-tRNA only in the presence of EF-Ts and at low ribosomal activity. Our in vitro observations have been extrapolated to in vivo conditions with conclusions as follows: Under strong amino acid starvation ppGpp in twofold excess over GTP cannot reduce significantly the elongation rate of ribosomes and thereby restore the errors to their normal levels as in the stringent response. Under weak starvation, in contrast, a significant rate reduction can be achieved by the trapping of EF-Ts in complex with TuppGpp.
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PMID:ppGpp inhibition of elongation factors Tu, G and Ts during polypeptide synthesis. 639 24


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