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)

1. When Tetrahymena were deprived of nutrients 50% of the polysomes disaggregated within 20 min and 20% of the total RNA broke down in 2 h. Ribosomal RNA accounted for 75% of the RNA breakdown. 2. RNA labelled by a long incubation with [14C]uridine was stable in growing cells and in the presence of actinomycin D, but broke down at the same rate as bulk RNA in starved cells. 3. The following substances inhibited the loss of RNA during starvation: cycloheximide (which inhibited both polysome disaggregation and protein synthesis), inhibitors of energy metabolism and puromycin (all of which caused polysome disaggregation and inhibited protein synthesis), and chloroquine and 7-amino-1-chloro-3-L-tosylamidoheptan-2-one ('TLCK') (neither of which affected polysomes or protein synthesis). 4. Starvation appears to activate a ribosome degradation mechanism that may involve lysosomal and non-lysosomal enzymes.
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PMID:The breakdown of Tetrahymena ribosomes in vivo. The effects of inhibitors. 618 38

Seven strains of normal human cells (fibroblastic, skin epithelioid, and amniotic) ceased to proliferate in medium depleted of free calcium ion by titration with ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), whereas the growth of 9 of 10 human melanoma cell lines was not affected. Fibroblasts showed a rapid drop in thymidine pool size and decreased incorporation of thymidine and uridine when treated with EGTA, followed during the next 48 hr by a decrease in plasma membrane potential and by development of a proliferative block in the G1 phase of the cell cycle. The calcium-independent melanoma line MM96 exhibited an early decrease in thymidine pool size and enhanced incorporation of nucleosides but continued to proliferate with little perturbation of the cell cycle or change in membrane potential. Tumor cell DNA may therefore be selectively labeled in the presence of normal cells. The anomalous, calcium-dependent melanoma line (MM170) showed an immediate increase in the thymidine pool size and in nucleoside incorporation and subsequently accumulated in G1 and G2 with diminution of membrane potential and of DNA and RNA synthesis. The proliferative block in MM170 cells could be reversed by addition of calcium ion or by replacement with control medium. Addition to the medium of all 8 nucleosides (50 microM), singly or together, did not prevent EGTA-induced cytostasis in fibroblasts or MM170; transport of thymidine across the cell membrane was enhanced by 24-hr EGTA treatment in fibroblasts, MM96, and MM170. Thus, although calcium affected thymidine utilization rapidly and differently in each of the three cell types, nucleoside starvation per se did not appear to be responsible for either type of proliferative block.
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PMID:Effects of calcium depletion on human cells in vitro and the anomalous behavior of the human melanoma cell line MM170. 618 41

The correlation between protein synthesis and the nuclear division cycle in Neurospora crassa hyphae was studied by inhibiting protein accumulation by two different experimental procedures: (1) starvation for lysine in a lysine-requiring mutant (lys-1); and (2) addition of cycloheximide. Lysine starvation in a lys-1 strain of N. crassa quickly blocked the nuclear division cycle and nuclei accumulated in G1 phase, as judged by their DNA content. After re-addition of lysine to starved cultures, a discontinuous pattern of uridine incorporation into DNA can be seen, showing that the nuclei were well synchronized. On the other hand, treatment with cycloheximide caused the arrest of a large proportion of the nuclei, also, in the G2 phase of the cell cycle. These results indicate that inhibition of protein synthesis may have multiple effects on the cell cycle in N. crassa and that, while moderate inhibition specifically blocks nuclei at a regulatory point in late G1, strong or complete inhibition demonstrates requirement for protein synthesis at other points in the cycle that are not necessarily regulatory points.
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PMID:Control points in Neurospora crassa nuclear division cycle: different effects of the inhibition of protein accumulation. 622 4

Certain strains of Escherichia coli mistranslate at very high frequencies when starved for asparagine or histidine. This mistranslation is the result of misreading events on the ribosome. The introduction of a hisT mutation into such a strain decreases the frequency of mistranslation during histidine starvation but not during asparagine starvation. The most likely explanation is that the replacement of the pseudouridine residue in the anticodon loop of glutamine specific transfer ribonucleic acid by uridine in hisT mutants leads to an increase in fidelity of transfer ribonucleic acid function. The hisT gene in Escherichia coli has also been more accurately mapped, giving the gene order purF-hisT-aroC-fadL-dsdA.
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PMID:Specific mistranslation in hisT mutants of Escherichia coli. 675 59

We present here a detailed analysis of the effect of amino acid starvation and the addition of cycloheximide on RNA metabolism of yeast cells and spheroplasts. These effects have been studied at the level of uridine phosphorylation, methylation of rRNA, and biosynthesis of 35 S, 4 S, and 5 S RNA species. Amino acid starvation inhibits the phosphorylation of uridine assigned for RNA synthesis more than that for other metabolic processes. This implies that a salvage pathway for the synthesis of UMP and CMP is regulated by the rate of transcription and perhaps is localized in the nucleus. The rate of rRNA methylation is not coupled with the rate of transcription; therefore, quantitation of 35 S RNA synthesis (yeast rRNA primary transcript by [methyl-3H]methionine labeling is unreliable. Biosynthesis of 35 S RNA ceases immediately after the cells are transferred to an amino-acid-deficient medium; at a later time 4 S and 5 S RNAs are also inhibited. Therefore, coordination and noncoordination in the stringent response of these RNA species depend upon the time of starvation. Although addition of a small dose (less than 1.0 microgram/ml) of cycloheximide to starved yeast spheroplasts does not alter the rate of uridine phosphorylation, it increases the rate of entrance of uridine into total RNA. This effect is of greater magnitude in 4 S and 5 S than in 35 S RNA. Since the drug does not alter the rate of decay of 35 S RNA that takes place in starvation, it has a selective effect on transcription. A similar small dose, however, produces inhibition of transcription of all these RNA species in nonstarved conditions. This opposite effect of the drug appears to be a characteristic feature of RNA metabolism in eukaryotes.
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PMID:The stringent and relaxed phenomena in Saccharomyces cerevisiae. 698 74

PALA (N-phosphonoacetyl-L-aspartate) impairs de novo pyrimidine biosynthesis by inhibiting the enzyme aspartate transcarbamylase. During cancer chemotherapy trials the drug was given by weekly intravenous infusion. Seizures developed in 9 (11%) of the first 80 patients to receive a total dose of 9 gm/m2 or more. Seven of the affected patients had structural brain lesions; they developed seizures at a lower total dose (median of 16.4 gm/m2) than the 2 patients without clinically detectable brain lesions (115 to 130 gm/m2). Reversible encephalopathy was observed in 6 (7.5%) additional patients without clinically detectable cause other than PALA. Both seizures and encephalopathy began after the second dose of PALA or later. Experiments in rats demonstrated similar delayed-onset seizures after two or three combined systemic and intracerebral doses of PALA at 4-day intervals. Concurrent administration of uridine or carbamyl aspartate prevented the development of seizures in rats, indicating that pyrimidine starvation of the central nervous system was responsible for PALA neurotoxicity.
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PMID:Neurotoxicity of the pyrimidine synthesis inhibitor N-phosphonoacetyl-L-aspartate. 712 6

Continuously regenerating stratified squamous epithelia form an interesting model for examining mechanisms controlling the balance between rates of cell formation and cell maturation and death. Previous investigations of epidermal metabolism have been mainly based on single enzyme assays which may not form a reliable guide to changing rates of flux through metabolic pathways. Methods for in vitro assays of rates of glycolysis, protein synthesis and RNA synthesis of epidermal sheets free from dermal contamination were developed and used to examine rates of epidermal metabolism after experimental alteration of rates of epidermal proliferation. Starvation resulted in a 45-53% reduction in the in vivo epidermal labeling index and a 49-56% reduction in glycolysis and incorporation of amino acids assayed in vitro. Induction of epidermal hyperplasia with hexadecane resulted in a 4-fold increase in labeling index, a 6-fold increase in vitro glycolysis and a 3 to 4-fold increase in in vitro assays of incorporation of amino acids and uridine. Hyperplastic epidermis also showed an increased rate of incorporation of histidine (a marker for keratokyalin synthesis) relative to leucine (a marker for basal cell protein synthesis) indicating a change in maturation. The results suggest mechanisms linking rates of cell proliferation and death and indicate the possible value of such assays investigating these mechanisms.
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PMID:An examination of the relationship between experimentally altered rates of epidermal proliferations and rates of epidermal metabolism assayed in vitro. 738 Dec 31

The aim of this study was to evaluate whether food intake modulates experimental tumour growth by acute alterations in the energy state and blood flow of the tumour, and if so whether such changes are related to alterations in the enzyme ornithinedecarboxylase (ODC) and DNA synthesis. Inbred mice (C57BL/J) bearing a syngeneic undifferentiated and rapidly growing tumour were used. The tumour levels of high energy phosphates were measured in vivo by 31-P-NMR spectroscopy and biochemically following tissue extraction. DNA synthesis was estimated by measuring the incorporation of bromodeoxy-uridine into tumour DNA. Difluoro-methylornithine (DFMO) was used to inhibit ODC-activity. Tumour blood flow was estimated by a 132Xe local clearance technique. Tumour progression was associated with a significant decrease in tumour tissue high energy phosphates. Acute starvation decreased DNA-synthesis and tumour energy charge as well as its PCr/Pi which were rapidly normalised during subsequent refeeding. These changes were related to similar alterations in tumour blood flow. The inorganic phosphate (Pi) resonance and the resonances in the phosphomonoester (PME) region were considerably increased in tumour tissue. Inhibition of ODC-activity by DFMO decreased DNA-synthesis, which was associated with a secondary increase in tumour high energy phosphates probably due to a lowered energy demand for tumour cell division. The results demonstrate that host undernutrition was translated into retarded tumour growth associated with a decrease in the energy state and blood flow of the tumour. The results have bearing for the evaluation and planning of all treatment protocols with potential influence on food intake in experimental tumour-bearing animals.
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PMID:Energetics of nutrition and polyamine-related tumor growth alterations in experimental cancer. 839 89

Phosphoribosyl diphosphate-lacking (delta prs) mutant strains of Escherichia coli require NAD, guanosine, uridine, histidine, and tryptophan for growth. NAD is required by phosphoribosyl diphosphate-lacking mutants because of lack of one of the substrates for the quinolinate phosphoribosyltransferase reaction, an enzyme of the NAD de novo pathway. Several NAD-independent mutants of a host from which prs had been deleted were isolated; all of them were shown to have lesions in the pstSCAB-phoU operon, in which mutations lead to derepression of the Pho regulon. In addition NAD-independent growth was dependent on a functional quinolinate phosphoribosyltransferase. The prs suppressor mutations led to the synthesis of a new phosphoryl compound that may act as a precursor for a new NAD biosynthetic pathway. This compound may be synthesized by the product of an unknown phosphate starvation-inducible gene of the Pho regulon because the ability of pst or phoU mutations to suppress the NAD requirement requires PhoB, the transcriptional activator of the Pho regulon.
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PMID:Phosphoribosyl diphosphate synthetase-independent NAD de novo synthesis in Escherichia coli: a new phenotype of phosphate regulon mutants. 855 May 5

Isoprinosine (IPS) is a synthetic drug whose antiviral effect on rotavirus replication in vitro has been characterized in terms of the decrease in metachromasia after acridine orange staining. The present study describes the effect of IPS on the synthesis of viral RNA in vitro. MA-104 cell cultures infected with simian rotavirus strain SA-11 were incubated with zero, 250, 500 and 1,000 micrograms/ml IPS and 22, 24, 48, 52, 72 and 76 h after infection the cultures were submitted to a 1-h starvation period, followed by a 2-h pulse with 10 microCi/ml of [3H]-uridine. The homogenates of virus-infected cultures treated or not with IPS were submitted to phenol/chloroform extraction followed by polyacrylamide gel electrophoresis. The amount of radioactivity in viral RNA eluted from the gel strips was determined. Inhibition of viral RNA synthesis was highest at the IPS concentration of 1,000 micrograms/ml at 72 h after infection, corresponding to 78% inhibition. Although the results obtained in vitro suggest that IPS may be useful for the treatment of rotavirus infection, an in vivo demonstration of its efficacy is needed.
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PMID:Effect of isoprinosine on rotavirus replication in vitro. 873 52


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