Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Saccharomyces cerevisiae X2180-1A synthesizes two forms of asparaginase: L-asparaginase I, an internal constitutive enzyme, and asparaginase II, an external enzyme which is secreted in response to nitrogen starvation. The two enzymes are biochemically and genetically distinct. The structural gene for asparaginase I (asp 1) is closely linked to the trp 4 gene on chromosome IV. The gene controlling the synthesis of asparaginase II is not linked to either the trp 4 or asp 1 genes. The rate of biosynthesis of asparaginase II is unaltered in yeast strains carrying the structural gene mutation for asparaginase I. Asparaginase II has been purified approximately 300-fold from crude extracts of Saccharomyces by heat and pH treatment, ethanol fractionation, ammonium sulfate fractionation followed by Sephadex G-25 chromatography, and DEAE-cellulose chromatography. Multiple activity peaks were obtained which, upon gas chromatographic analysis, exhibit varying mannose to protein ratios. Asparaginase I has been purified approximately 100-fold from crude extracts of Saccharomyces by protamine sulfate treatment, ammonium sulfate fractionation, gel permeation chromatography, and DEAE-cellulose chromatography. No carbohydrate component was observed upon gas chromatographic analysis. Comparative kinetic and analytic studies show the two enzymes have little in common except their ability to hydrolyze L-asparagine to L-aspartic acid and ammonia.
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PMID:Characterization of two forms of asparaginase in Saccharomyces cerevisiae. 34 21

The growth of the eucaryotic microorganism Dictyostelium discoideum in liquid culture was completely inhibited by the aspartic acid analog hadacidin (N-formylhydroxyamino-acetic acid). Growth arrest occurred both in chemically defined medium and in complex growth medium containing aspartic acid and AMP precursors such as adenine and adenosine. Although these compounds could not overcome the effect of hadacidin, growth was restored if cells were washed and resuspended in fresh growth medium. Additional experiments showed that D. discoideum contains adenylosuccinate synthetase, the enzyme which catalyzes the synthesis of adenylosuccinate from IMP, aspartic acid, and GTP in the de novo biosynthesis of purines. A partially purified preparation of this enzyme was obtained, and the effect of hadacidin on its activity was studied. We found that maximum inhibition of the D. discoideum activity occurs at a ratio of aspartic acid to hadacidin of 5:1, suggesting that the affinity of the drug for this enzyme is less than for the enzyme from rabbit muscle and plants but greater than for that from Escherichia coli. The effect of the drug can be overcome by a 10-fold excess of aspartic acid, suggesting that the drug acts as a competitive inhibitor. A comparison of the adenylosuccinate synthetase activity levels at various stages of growth showed that its specific activity decreases about 60% as cells enter the stationary growth phase, and decreases about 75% after starvation for 2 h. Further studies showed that in cells treated with hadacidin the rate of uptake of exogenous nutrients is reduced about 75% and that these cells are more resistant to rupture by osmotic shock. While the results of this study are consistent with the proposal that growth arrest is contingent upon inhibition of adenylosuccinate synthetase activity, they also suggest that, as a consequence of this inhibition, some physiological properties of the cell have been altered.
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PMID:Effect of hadacidin on growth and adenylosuccinate synthetase activity of Dictyostelium discoideum. 56 51

Arterial plasma amino acids were measured in 27 patients with serious septic complications after operation, 15 patients following reduction of femoral shaft fractures and nine control patients on the first and third days following uneventful major abdominal surgery. Amino acid concentrations in the controls were similar to those which have been reported during early starvation. The amino acid patterns seen in all groups did not resemble that previously observed following glucocorticoid administration. In the patients with infection, mean phenylalanine concentration (108.0 +/- 46.9 mumoles per liter) was significantly greater than in the controls on the first (p greater than 0.001) or third (p less than 0.001) postoperative days. Four of the septic patients with hyperphenylalaninemia also had elevated arterial methionine concentrations. These observations suggest that many of the patients with sepsis had seriously impaired liver metabolism. In patients with fractures, the concentrations of ornithine (p less than 0.001), taurine (p less than 0.05), and aspartic acid (p less than 0.05) were lower than in controls. No other significant differences of amino acid concentrations were observed. It is difficult to relate these differences to a specific metabolic abnormality.
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PMID:Arterial plasma amino acids in patients with serious postoperative infection and in patients with major fractures. 125 95

The transport of L-glutamic acid has been studied in skin-derived diploid human fibroblasts. Competition analysis in the presence and absence of Na+ and mathematical discrimination by nonlinear regression indicated that L-glutamic acid enters the cell by at least three transport systems: 1) a high affinity Na+-dependent system which has been found to be identical to the previously described system for anionic amino acids (Gazzola, G. C., Dall'Asta, V., Bussolati, O., Makowske, M., and Christensen, H. N. (1981) J. Biol. Chem. 256, 6054-6059) and which is provisionally designated as System X-AG; this route was shared by L-aspartic acid; 2) a low affinity Na+-dependent system resembling the ASC System for neutral amino acids (Franchi-Gazzola, R., Gazzola, G. C., Dall'Asta, V., and Guidotti, G. G. (1982) J. Biol. Chem. 257, 9582-9587); its reactivity toward L-glutamic acid was strongly inhibited by L-serine, but not by 2-(methyl-amino)isobutyric acid; and 3) a Na+-independent system similar to System XC- described in fetal human lung fibroblasts (Bannai, S., and Kitamura, E. (1980) J. Biol. Chem. 255, 2372-2376). The XC- system served for L-glutamic acid and L-cystine, the latter amino acid behaving as a potent inhibitor of L-glutamic acid uptake. Amino acid starvation did not change the uptake of L-glutamic acid by the two Na+-dependent systems, but enhanced the activity of System XC- by increasing its Vmax. L-Glutamic acid transport was also affected by the density of the culture. An increased cell density lowered the uptake of the amino acid by Systems ASC and XC- and promoted the uptake by System X-AG. All these variations were dependent upon changes in Vmax.
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PMID:Pathways of L-glutamic acid transport in cultured human fibroblasts. 613 63

The general control of amino acid biosynthesis was investigated in Candida spec. EH 15/D, using single and double mutant auxotrophic strains and prototrophic revertants starved for their required amino acids. These experiments show that starvation for lysine, histidine, arginine, leucine, threonine, proline, serine, methionine, homoserine, asparagine, glutamic acid or aspartic acid can result in derepression of enzymes. A correlation was found between the degree of derepression, growth of strains, and concentration of required amino acids. The amino acids pool pattern of mutants and revertants is different from that in the wild type strain.
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PMID:[General control of amino acid biosynthesis in mutants of Candida spec. EH 15/D]. 663 44

The effect of a number of conditions on the amount of cyanophycin granule polypeptide [multi-L-arginyl poly(L-aspartic acid)] formed in the unicellular cyanobacterium Aphanocapsa 6308 was determined. Light, CO2, sulfur, and phosphorus starvation as well as the addition of arginine to culture media increased the amount of cyanophycin granule polypeptide in cells when compared with that in cells grown under conditions optimal for growth. Nitrogen limitation and reduction of growth temperature to 30 degrees C decreased the amount of cyanophycin granule polypeptide on a dry-weight basis. Shift-up and shift-down experiments suggest cyanophycin granule polypeptide may be a reserve nitrogen polymer in Aphanocapsa 6308.
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PMID:Cyanophycin granule polypeptide formation and degradation in the cyanobacterium Aphanocapsa 6308. 676 88

L-Glutamate stimulates the liberation of arachidonic acid from mouse striatal neurons via the activation of N-methyl-D-aspartic acid (NMDA) receptors and by the joint stimulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and metabotropic receptors. In this study, we investigated whether starving cultured mouse striatal neurons of glucose would modify glutamatergic receptor-mediated arachidonic acid release. Glucose deprivation for 30 min led to enhancement of the NMDA-evoked release of arachidonic acid, compared with that observed in the presence of glucose. This enhanced response depended on both the concentration of glucose and the length of time of glucose deprivation. The enhanced NMDA response appeared to result from both a release of glutamate and the subsequent additional release of arachidonic acid due to the activation of AMPA and metabotropic receptors. Indeed, the increased NMDA response was completely reversed when extracellular glutamate was enzymatically removed. Moreover, glucose deprivation potentiated the combined AMPA/metabotropic receptor-evoked release of arachidonic acid, even in the absence of extracellular glutamate. However, removing glucose did not improve the calcium rise induced by AMPA or NMDA. The ATP-evoked release of arachidonic acid from striatal astrocytes was not altered by glucose starvation. In summary, glucose deprivation affected two properties of striatal neurons: (a) it induced an NMDA-evoked release of glutamate from striatal neurons and (b) it selectively potentiated the AMPA/(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-evoked release of [3H]arachidonic acid without altering the authentic NMDA-mediated response.
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PMID:Glucose regulates glutamate-evoked arachidonic acid release from cultured striatal neurons. 779 Aug 66

Escherichia coli contains two major systems for transporting inorganic phosphate (P(i)). The low-affinity P(i) transporter (pitA) is expressed constitutively and is dependent on the proton motive force, while the high-affinity Pst system (pstSCAB) is induced at low external P(i) concentrations by the pho regulon and is an ABC transporter. We isolated a third putative P(i) transport gene, pitB, from E. coli K-12 and present evidence that pitB encodes a functional P(i) transporter that may be repressed at low P(i) levels by the pho regulon. While a pitB(+) cosmid clone allowed growth on medium containing 500 microM P(i), E. coli with wild-type genomic pitB (pitA Delta pstC345 double mutant) was unable to grow under these conditions, making it indistinguishable from a pitA pitB Delta pstC345 triple mutant. The mutation Delta pstC345 constitutively activates the pho regulon, which is normally induced by phosphate starvation. Removal of pho regulation by deleting the phoB-phoR operon allowed the pitB(+) pitA Delta pstC345 strain to utilize P(i), with P(i) uptake rates significantly higher than background levels. In addition, the apparent K(m) of PitB decreased with increased levels of protein expression, suggesting that there is also regulation of the PitB protein. Strain K-10 contains a nonfunctional pitA gene and lacks Pit activity when the Pst system is mutated. The pitA mutation was identified as a single base change, causing an aspartic acid to replace glycine 220. This mutation greatly decreased the amount of PitA protein present in cell membranes, indicating that the aspartic acid substitution disrupts protein structure.
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PMID:Characterization of PitA and PitB from Escherichia coli. 1148 53

Eisenstadt, Jerome M. (Brandeis University, Waltham, Mass.) and Harold P. Klein. Evidence for the de novo synthesis of the alpha-amylase of Pseudomonas saccharophila. J. Bacteriol. 82:798-807. 1961.-Chloramphenicol at a concentration of 20 mug per ml inhibited the appearance of the inducible alpha-amylase of Pseudomonas saccharophila. This inhibition was observed when induction was attempted in buffer or in a complete medium. Preinduced cells were also prevented from forming this enzyme under similar conditions. Under all the conditions tested, there was no lag in chloramphenicol inhibition, thus suggesting an absence of any protein precursor in amylase formation. Cells suspended in a complete medium without a nitrogen source lost their capacity to form this enzyme when subsequently induced in buffer. When cells were grown in the presence of radioactive sulfate and then subjected to starvation, the radioactivity of the amino acid pool diminished only slightly. However, examination of the free amino acid pool by paper chromatography showed that the loss of enzyme inducibility was accompanied by the disappearance of glutamine, aspartic acid, and a third, unidentified, compound. Enzyme-forming ability was restored by the addition, to starved cells of casein hydrolysate, glutamate, glutamine, or aspartate. Other amino acids tested were ineffective in this regard. When cells were induced in buffer in the presence of labeled methionine, amylase was formed at a linear rate over a 3-hr period. Furthermore, both the cellular proteins and the extracellular amylase became labeled at a linear rate. These observations are discussed in relation to the problem of protein turnover, and are interpreted as evidence for the de novo synthesis of alpha-amylase in this organism.
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PMID:Evidence for the de novo synthesis of the alpha-amylase of Pseudomonas saccharophila. 1388 95

D-Tyr-tRNATyr deacylase cleaves the ester bond between a tRNA molecule and a D-amino acid. In Escherichia coli, inactivation of the gene (dtd) encoding this deacylase increases the toxicity of several D-amino acids including D-tyrosine, D-tryptophan, and D-aspartic acid. Here, we demonstrate that, in a Deltadtd cell grown in the presence of 2.4 mm D-tyrosine, approximately 40% of the total tRNATyr pool is converted into D-Tyr-tRNATyr. No D-Tyr-tRNATyr is observed in dtd+ cells. In addition, we observe that overproduction of tRNATyr, tRNATrp, or tRNAAsp protects a Deltadtd mutant strain against the toxic effect of D-tyrosine, D-tryptophan, or D-aspartic acid, respectively. In the case of D-tyrosine, we show that the protection is accounted for by an increase in the concentration of L-Tyr-tRNATyr proportional to that of overproduced tRNATyr. Altogether, these results indicate that, by accumulating in vivo, high amounts of D-Tyr-tRNATyr cause a starvation for L-Tyr-tRNATyr. The deacylase prevents the starvation by hydrolyzing D-Tyr-tRNATyr. Overproduction of tRNATyr also relieves the starvation by increasing the amount of cellular L-Tyr-tRNATyr available for translation.
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PMID:Formation of D-tyrosyl-tRNATyr accounts for the toxicity of D-tyrosine toward Escherichia coli. 1529 42


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