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

In submerged grown hyphae of Penicillium cyclopium the activities of seven transport systems could be distinguished which share in the uptake of L-arginine, L-glutamic acid, L-phenylalanine and L-leucine. They include the specific systems a (accepting L-arginine and L-lysine), b (L-phenylalanine, L-tyrosine), c (L-glutamic acid) and d (L-leucine), system I (a 'general amino-acid permease') and the low-affinity systems II and III, which accept acidic or basic amino acids, respectively, but also L-phenylalanine. In nutrient-sufficient cells, systems I, II and III remain repressed; uptake is dominated by the specific systems b, c, d and a, the latter reaching its maximum activity. Nitrogen starvation is the most powerful signal for the development of systems I, II and III, whereas, in carbon-starved cells, systems b, c and d reach maximum activities. The development of the general amino-acid permease in nitrogen-starved cells requires both translational and--with a few hours delay--transcriptional events as indicated by the influence of cycloheximide and 5-fluorouracil. The uptake of all amino acids is accompanied by a transient acidification of the cellular interior. Short-time preaccumulation of several anions, such as citrate, alpha-oxo-glutarate, glutamate (but not glutamine), increases the initial rate of amino-acid uptake at a pH above the optimum. Uncouplers inhibit the uptake not only under aerobic but also under anaerobic conditions, where the ATP content is not influenced by these compounds. These findings point to an H+/amino acid symport, which is tightly connected with the recycling of the incoming protons by the plasmalemma H+-ATPase.
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PMID:Kinetic properties, nutrient-dependent regulation and energy coupling of amino-acid transport systems in Penicillium cyclopium. 256 28

The ARO3 gene encodes one of two 3-deoxy-D-arabino-heptulosonate-7-phosphate isoenzymes in Saccharomyces cerevisiae catalyzing the first step in the biosynthesis of aromatic amino acids. The ARO3-encoded 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (EC 4.1.2.15) is feedback inhibited by phenylalanine; its isoenzyme, the ARO4 gene product, is inhibited by tyrosine. Both genes ARO3 and ARO4 are strongly regulated under the general control regulatory system. Cells carrying only one intact isogene are phenotypically indistinguishable from a wild-type strain when grown on minimal medium. The complete functional ARO3 promoter comprises 231 base pairs and contains only one TGACTA binding site for the general control activator protein GCN4. Mutating this element to TTACTA inhibits binding of GCN4 and results in a decreased basal level of ARO3 gene product and slow growth of a strain defective in its isogene ARO4. In addition, ARO3 gene expression cannot be elevated under amino acid starvation conditions. An ARO3 aro4 strain with gcn4 genetic background has the same phenotype of low ARO3 gene expression and slow growth. The amount of GCN4 protein present in repressed wild-type cells therefore seems to contribute to a basal level of ARO3 gene expression. The general control activator GCN4 has thus two functions: (i) to maintain a basal level of ARO3 transcription (basal control) in the presence of amino acids and (ii) to derepress the ARO3 gene to a higher transcription rate under amino acid starvation (general control).
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PMID:The general control activator protein GCN4 is essential for a basal level of ARO3 gene expression in Saccharomyces cerevisiae. 256 34

The degradation of intracellular protein and other cytoplasmic macromolecules in liver is an ongoing process that regulates cytoplasmic mass and provides amino acids for energy and other metabolic uses early in starvation. Cellular proteins are conveniently divided into two general classes according to readily discernable differences in average rates of turnover. A short-lived class, having a half-life of approximately 10 min, comprises about 0.6% of total protein. Its degradation is not physiologically controlled, and the mechanism is probably nonlysosomal in nature. The second or long-lived group, with an average half-life 250 times greater, constitutes more than 99% of the cell's protein. By contrast, its breakdown is strongly regulated, and the site of catabolism is believed to be the vacuolar-lysosomal system. Cytoplasmic sequestration by lysosomes can be divided into two categories; macro- and microautophagy. The first is induced by amino acid and/or insulin deprivation. Amino acids are considered to be primary regulators, since they can control this process over the full range of induced proteolysis in the absence of hormones. Glucagon, cyclic AMP, and beta-agonists also stimulate macroautophagy in hepatocytes but have opposite effects in myocytes. Micrautophagy differs from the former in that the cytoplasmic "bite" is smaller and the uptake process is not acutely regulated. However, the latter does decrease during starvation in parallel with basal proteolysis, effects that might be linked to the loss of endoplasmic reticulum. The primary control of macroautophagy is accomplished through a small group of direct regulators (Leu, Tyr/Phe, Gln, Pro, Met, His, and Trp) and a specific coregulatory action of alanine. As a group, regulatory amino acids produce direct inhibitory responses in the perfused rat liver that are identical to those of the complete amino acid mixture at 0.5x and 4x (times) normal plasma concentrations. However, they lose effectiveness almost completely within a narrow zone centered at normal levels, a loss that can be abolished by the addition of alanine at its normal plasma concentration (0.5 mM). At this level, alanine does not inhibit directly. Interestingly, this zonal loss is also eliminated by insulin. Glucagon, though, specifically blocks the initial inhibition evoked by 0.5x amino acid mixtures and thus induces maximal rates of protein degradation at normal amino acid concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism and regulation of protein degradation in liver. 264 36

It has previously been shown that the phenylalanine codon UUC encoding residue 8 of the Escherichia coli argI gene product, ornithine transcarbamylase, is misread as leucine at a high frequency during phenylalanine starvation. However, no misreading of the UUU encoding residue 3 was observed under these conditions. Using oligonucleotide-directed, site-specific mutagenesis, we have constructed mutants where these codons have been changed. Using these mutant argI genes we see a high level of mistranslation at position 8 during phenylalanine starvation whether the codon is UUU or UUC. With either codon at position 3 we see no leucine substitution. We also constructed a gene with a leucine codon at position 3. The product of this latter mutated gene is stable and active, indicating that preferential turnover of mistranslated protein is not obscuring an otherwise high rate of misreading. This would seem to indicate that it is the context rather than the particular phenylalanine codon which is important in determining these misreading levels.
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PMID:Context specific misreading of phenylalanine codons. 268 41

We constructed Schizosaccharomyces pombe strains that carry phenylalanine, instead of arginine, as residue 116 of calmodulin by site-directed mutagenesis of the cam1 gene. Whereas haploid strains carrying the mutant allele, designated cam1-F116, exhibit no defects in growth and mating, diploid strains homozygous for cam1-F116 are deficient in sporulation. The four nuclei generated by the two serial meiotic divisions are not encapsulated in these diploids. The mutation is recessive. Semiquantitative analysis using polyclonal antibodies showed that vegetatively growing cam1-F116 cells have a smaller amount of calmodulin than wild-type cells. The quantitative difference becomes more remarkable if the cells are starved for nitrogen, which is a condition for induction of sporulation. In addition to this in vivo observation, we showed in vitro that the mutant protein is susceptible to a proteolytic activity induced by nitrogen starvation that hardly affects the wild-type calmodulin. Thus, the sporulation deficiency of the cam1-F116 mutant may be ascribed to shortage of calmodulin due to proteolysis of the mutant molecules under nitrogen starvation. Two other mutations at position 116 resulted in similar but leakier Spo- phenotypes.
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PMID:Substitution at position 116 of Schizosaccharomyces pombe calmodulin decreases its stability under nitrogen starvation and results in a sporulation-deficient phenotype. 269 71

In this article we summarize evidence for a pathway by which cytosolic proteins can be selectively taken up and degraded within lysosomes. Serum deprivation of cells in culture activates this pathway, and only proteins that contain peptide sequences related to KFERQ (lysine, phenylalanine, glutamic acid, arginine, glutamine) are degraded at enhanced rates. Approximately 30% of intracellular proteins contain such peptide sequences, and we speculate about the physiological relevance of the selective degradation of these proteins in response to serum withdrawal. Several rat tissues also contain proteins with peptide sequences related to KFERQ, and the amount of these proteins is reduced in response to starvation. Finally, we present recent results suggesting that this selective uptake of cytosolic proteins by lysosomes is not through classical macroautophagic pathways. Instead, the selective uptake may be similar to other protein sorting pathways such as protein translocation through the endoplasmic reticulum or protein import into mitochondria.
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PMID:Lysosomal degradation of microinjected proteins. 270 96

Previously we showed that starvation of HL-60 promyelocytic leukemia cells for a single essential amino acid induced irreversible differentiation into more mature monocyte-like cells. Although not an essential amino acid, glutamine is important in the growth of normal and neoplastic cells. The glutamine analogue, alpha S,5S-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) inhibits several glutamine-utilizing enzymes and therefore depletes cells of certain metabolic end products. The current study was designed to examine in vitro the effects of acivicin on growth and differentiation of several established human myeloid leukemia cell lines, including the HL-60 cell line, and of freshly isolated cells from patients with acute nonlymphocytic leukemia (ANLL). Four-day culture of HL-60 cells with acivicin at concentrations of 0.1 to 10.0 micrograms/mL (0.56 to 56 nmol/L) decreased cell growth by 33% to 88% as compared with untreated control cells. Viability of cells was greater than 92% for untreated cells and 93% to 41% for acivicin-treated cells. Cells treated with acivicin differentiated along a monocytic pathway as shown by increased H2O2 production and alpha-naphthyl butyrate esterase (NSE) content. Differentiation was time and dose dependent, and was irreversible. Changes in H2O2 production and NSE content were partially abrogated by co-culture with 10 mmol/L exogenous cytidine and guanosine but not by co-culture with other nucleosides or glutamine. At these concentrations of acivicin, differentiation was associated with expression of the N-formyl-methyl-leucyl-phenylalanine-receptor (FMLP-R) on 8% to 29% of cells as compared with 8% for control cells. Acivicin potentiated the differentiating effects of interferon-gamma, tumor necrosis factor, dihydroxyvitamin D3, dimethylsulfoxide, and retinoic acid. Culture of cells from the U937 (monoblastic), K562 (erythroleukemia), and KG-1 (myeloblastic) cell lines resulted in decreased growth and viability, but not consistently in differentiation. Acivicin decreased survival of freshly isolated ANLL cells and increased their H2O2 production and NSE content. These results suggest that the glutamine analogue acivicin may be useful as a differentiating agent with antileukemia activity in patients with ANLL.
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PMID:Monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells induced by the glutamine antagonist acivicin. 279 Jan 98

Starvation for phenylalanine led to leucine misincorporation frequencies of 0.1 and 0.6 at UUC codons in the argI transcript of Escherichia coli, but no detectable misincorporation at a UUU codon. Under similar starvation conditions the relative synthesis of full sized MS2 coat protein, encoded by the RNA virus or a DNA copy, is greatly reduced, preventing analysis of the protein. This reduction in amount is unaffected by a rpsL mutation.
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PMID:Mistranslation during phenylalanine starvation. 301 46

When amino acids that are generally transported through the A system are added to derepressed cultures of CHO-K1 cells or to cultures that are undergoing starvation-derepression, as in the co-repressor (co-r), co-inactivator (co-i), (co-ri) assay, the A system undergoes trans-inhibition, inactivation, and repression. The effect of inactivation and repression is not related to the ability of amino acids to bind to the A system transporter but supports a model in which these amino acids act as co-r's/co-i's, and by binding to a aporepressor/inactivator (apo-ri), the product of gene R1, convert it into a repressor/inactivator (ri). For example, beta-alanine acts as a strong co-r but does not inhibit proline transport through the A system. Hydroxyproline and histidine, although poor inhibitors of proline transport, are very effective as co-ri's. Diaminobutyrate, phenylalanine, alpha-keto-glutarate, pyro-glutamate, isoleucine, and valine, compounds that inhibit A system transport, listed in decreasing order of effectiveness, are all equally poor as co-ri's. Also the Km for the transport of 2-(methylamino)isobutyric acid (MeAIB) through the A system is two times the concentration of MeAIB required to produce one-half inactivation. Amino acid effectors and mutation can modify the conversion of the apo-ri to repressor (r) and inactivator (i). The apo-ri is converted by alanine, serine, proline, and MeAIB to ri, by beta-alanine and tryptophane to r, and by hydroxyproline to r and reduced i. The full constitutive and partial constitutive mutants alar4 and alar2, respectively, are in the same complementation group. Alar4 has no active apo-ri while the rate of derepression of alar2 is twice and the inactivation rate is equal to that of the parent culture.
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PMID:Regulation of the A system of amino acid transport in Chinese hamster ovary cells, CHO-K1: the difference in specificity between the apo-repressor inactivator (apo-ri) and the transporter and the characterization of the proposed apo-ri. 308 25

The continuous turnover of intracellular protein and other macromolecules is a basic cellular process that serves, among other functions, to regulate cytoplasmic content and provide amino acids for ongoing oxidative and biosynthetic reactions during nutrient deprivation. The intensity of breakdown and pattern of regulation, though, vary widely among cells. Rat hepatocytes, for example, exhibit high absolute rates of proteolysis and regulatory effects that diminish during starvation, while corresponding responses in skeletal and cardiac muscle move in the opposite direction. It is also becoming apparent that effects of insulin and other acute regulatory agents on muscle breakdown are limited to nonmyofibrillar components. The latter may be sequestered and degraded within autophagic vacuoles, whereas myofibrillar proteins require an initial attack by calcium-dependent proteases in the cytosol. By contrast, most if not all of the breakdown of resident (long-lived) proteins as well as RNA in the hepatocyte can be explained by lysosomal mechanisms. The uptake of cytoplasmic components by lysosomes can be divided into two major categories, macroautophagy and micro- or basal autophagy. The first is induced by amino acid or insulin/serum deprivation. In the hepatocyte, amino acids alone can regulate this process almost instantaneously over two thirds of the full range of proteolysis, 4.5% to 1.5% per hour. Glucagon, cyclic AMP, and beta-agonists also stimulate macroautophagy in hepatocytes but have opposite effects in skeletal and cardiac myocytes. Basal autophagy differs from the macro type in that the cytoplasmic "bite" is smaller and sequestration is not acutely regulated. It is, however, adaptively decreased during starvation in parallel with absolute rates of basal turnover. Since endoplasmic reticulum comprises an appreciable fraction of the vacuolar content, volume sequestration would be compatible with the known heterogeneity of individual protein turnover if some proteins (or altered proteins) selectively bind to membranes. The amino acid control of macroautophagy in the hepatocyte is accomplished by a small group of direct inhibitors (Leu, Tyr/Phe, Gln, Pro, Met, Trp, and His) and the permissive effect of alanine whereas only leucine is involved in myocytes and adipocytes. Of unusual interest is the fact that the inhibitory amino acid group alone evokes responses in perfused livers that are identical to those of a complete plasma mixture at 0.5 and 4 times normal plasma levels but loses effectiveness almost completely at normal concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intracellular protein catabolism and its control during nutrient deprivation and supply. 330 Jul 46


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