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)

The intact extensor digitorum longus (EDL) preparation in rat is a well-documented model for assessing protein synthesis in skeletal muscle. Human muscle biopsy material has also been used, but the extent to which biopsy material is representative for evaluation of muscle protein synthesis has not been established. Therefore, the aim of this study was to compare protein synthesis in intact muscle and in muscle biopsy material simultaneously in rats. The animals (70 g) were divided into three groups: fed (n = 22), starved for 36 hours (n = 22), and refed for 24 hours (n = 19). Protein synthesis and RNA content were measured in each group. Protein synthesis was determined as the incorporation of 14-C-phenylalanine into muscle protein in the intact EDL muscle from one leg and in a muscle biopsy from the contralateral EDL muscle. The incorporation of 14-C-phenylalanine was linear over time in both preparations, but was consistently lower in the muscle biopsy compared with the intact muscle. The relative change in incorporation, in % of that obtained in the fed state, showed a decrease in incorporation after 36 hours of starvation, in both intact muscle and in muscle biopsy material, 33% +/- 10% and 42% +/- 6%, respectively. After 24 hours of refeeding, an overshoot in protein synthesis was seen, to 136% +/- 6% in the intact muscle and to 133% +/- 6% in the muscle biopsy, as compared with the fed state. The RNA content decreased during the starvation period from 21.6 +/- 0.7 to 14.5 +/- 0.4 mg RNA/g protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein synthesis in skeletal muscle during starvation and refeeding: comparison of data from intact muscle and muscle biopsy material. 170 Feb 58

With an in vitro poly(Phe) synthesis system we have tested recent models concerning translational accuracy in the stringent response during aminoacid starvation. We have found that cognate, deacylated tRNA of very high concentrations is unable to block the A-site. No influence of EF-Tu.ppGpp on ribosomal proofreading has been found. Alternative mechanisms to keep translational errors low by the stringent response are discussed.
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PMID:How does ppGpp affect translational accuracy in the stringent response? 172 24

Previous work suggested that the structural gene for the A system transporter and the mRNA for the alpha subunit of the Na+,K(+)-ATPase in Chinese hamster ovary cells CHO-K1 [wild type (WT)] are coordinately controlled by regulatory gene R1. This conclusion was based on analysis of a mutant for the A system, alar4. This mutant had a constitutive level of A system transport activity equal to the level found in derepressed WT cells and a 4 times increase in abundance of the alpha 1 subunit of Na+,K(+)-ATPase mRNA over that found in repressed WT. The level of Na+ per cell in alar4 was not significantly greater than that found in the WT. To further characterize the likely coregulation of both genes, we have studied the A system activity and Na+,K(+)-ATPase mRNA alpha 1-subunit levels in cells grown under various conditions that result in repression or derepression of the A system in the WT. System A activity increased up to 2-3 times the basal transport rate (repressed state) and Na+,K(+)-ATPase mRNA alpha 1-subunit levels showed a 3-fold increase after amino acid starvation (derepressed state). These changes occurred along with a decrease in intracellular Na+ levels. N-Methyl-alpha-aminoisobutyric acid and beta-alanine, previously shown to be corepressors for the A system, prevented to a similar extent A system derepression and Na+,K(+)-ATPase mRNA alpha 1-subunit accumulation. On the other hand, phenylalanine and lysine, amino acids that are not corepressors of the A system, failed to significantly prevent derepression of both genes. Hybrids between the WT and alar4 have the phenotype of the WT when grown under repressed conditions. These results give further support to the proposition that both the A system transporter and mRNA for the alpha 1 subunit of the Na+,K(+)-ATPase are coordinately controlled by regulatory gene R1 and elevated Na+ concentrations are not involved. No Na+,K(+)-ATPase activity was detected in derepressed cells. Activity was restored by the addition of monensin. However, this activity was no greater than that obtained in repressed cells. Indications are that the reduced Na+ content in derepressed cells inhibits Na+,K(+)-ATPase activity and that conditions that favored derepression do not allow for de novo synthesis of the Na+,K(+)-ATPase.
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PMID:Evidence for coordinate regulation of the A system for amino acid transport and the mRNA for the alpha 1 subunit of the Na+,K(+)-ATPase gene in Chinese hamster ovary cells. 184 56

This review focuses on the gene-enzyme relationships and the regulation of different levels of the aromatic amino acid biosynthetic pathway in a simple eukaryotic system, the unicellular yeast Saccharomyces cerevisiae. Most reactions of this branched pathway are common to all organisms which are able to synthesize tryptophan, phenylalanine, and tyrosine. The current knowledge about the two main control mechanisms of the yeast aromatic amino acid biosynthesis is reviewed. (i) At the transcriptional level, most structural genes are regulated by the transcriptional activator GCN4, the regulator of the general amino acid control network, which couples transcriptional derepression to amino acid starvation of numerous structural genes in multiple amino acid biosynthetic pathways. (ii) At the enzyme level, the carbon flow is controlled mainly by modulating the enzyme activities at the first step of the pathway and at the branch points by feedback action of the three aromatic amino acid end products. Implications of these findings for the relationship of S. cerevisiae to prokaryotic as well as to higher eukaryotic organisms and for general regulatory mechanisms occurring in a living cell such as initiation of transcription, enzyme regulation, and the regulation of a metabolic branch point are discussed.
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PMID:Aromatic amino acid biosynthesis in the yeast Saccharomyces cerevisiae: a model system for the regulation of a eukaryotic biosynthetic pathway. 194 92

Regulation of somatostatin gene expression was studied in the rat gastric antrum. Antral total RNA was isolated from animals during starvation and after refeeding, or under gastric neutralization by fundectomy or by omeprazole treatment. Northern blot analysis using cRNA probe synthesized from a cloned rat somatostatin cDNA demonstrated a single hybridizing band, approximately 850 nucleotides in length, which is present in the antrum. Quantitative slot blot analyses were able to detect significant changes of somatostatin mRNA levels in total RNA as low as 5 micrograms. Somatostatin mRNA levels increased significantly after 12 hours of fasting (144% of control) and remained elevated throughout the 4-day fasting period. Upon refeeding with solid food and phenylalanine, antral somatostatin returned to the prefasted level in 2 hours. Refeeding with olive oil or saline depressed somatostatin mRNA significantly within 30 to 60 minutes but did not attain the prefasted state. Fundectomy and omeprazole resulted in maximal inhibition of antral somatostatin mRNA levels by 77% and 78%, respectively. The present in vivo results indicate that somatostatin gene expression in the stomach is regulated by luminal factors that include pH and specific nutrients. Future studies based on this phenomenon can expand knowledge of the interactions between gastric endocrine cells and the gastric environment.
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PMID:Regulation of gastric somatostatin gene expression. 197 6

We review evidence for a pathway by which specific cytosolic proteins are targeted to lysosomes for degradation in cultured cells in response to serum withdrawal. This pathway is also activated by starvation in several rat tissues. The enhanced degradation is specific for a class of intracellular proteins containing peptide sequences related to residues 7 to 11 of ribonuclease A (RNase A). The amino acid sequence of this pentapeptide is lysine-phenylalanine-glutamate-arginine-glutamine, or, in single letter amino acid abbreviations, KFERQ. A heat shock protein of 73 kDa binds to such peptide regions in proteins and somehow mediates their transfer to lysosomes for degradation. The recent reconstitution of this lysosomal pathway of proteolysis in vitro should permit detailed mechanistic analysis of how proteins are directed to and translocated across lysosomal membranes.
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PMID:Targeting of cytosolic proteins to lysosomes for degradation. 207 87

Lysosomes take up and degrade intracellular proteins in cultured cells in response to serum deprivation, and in tissues of organisms in response to starvation. One mechanism by which proteins enter lysosomes for subsequent degradation requires that substrate proteins contain peptide sequences biochemically related to Lys-Phe-Glu-Arg-Gln (KFERQ).
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PMID:Peptide sequences that target cytosolic proteins for lysosomal proteolysis. 220 56

Although starvation is known to impair insulin-stimulated glucose disposal, whether it also induces resistance to insulin's antiproteolytic action on muscle is unknown. To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using [3H]phenylalanine (Phe) and [14C]leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150-min basal period, forearm local insulin concentration was selectively raised by approximately 25 muU/ml for 150 min by intra-arterial insulin infusion (0.02 mU.kg-1. min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P less than 0.02). Post-absorptively, forearm muscle exhibited a net release of Phe and Leu, which increased two- to threefold after the 60-h fast (P less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 0.02). After the 60-h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. We conclude that in short-term fasted humans 1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and 2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action.
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PMID:Effect of starvation on human muscle protein metabolism and its response to insulin. 222 Oct 49

Serum aminogram changes were prospectively studied in 95 patients with enteric fistula and intraabdominal infection who was under total parenteral nutrition (TPN) therapy with Anfuming 14s. In patients with sepsis and starvation, the aminogram showed remarkably low total free amino acids before TPN therapy. In 81 survivors, free amino acids increased gradually to normal in 2 weeks after use of TPN and in 14 dead cases increased rapidly to a significantly higher peak at terminal stage. Both in survivors and nonsurvivors, phenylalanine level remained high during the study. In response to infection, proline was also elevated but to a lesser degree; the ratio of branched chain amino acid (BCAA) to aromatic amino acid (AAA) was lower than normal and the decrease of arginine was parallel to the severity of infection. We conclude that the ideal amino acids preparation for the starvated and septic patients should be high in BCAA and arginine but low in phenylalanine, administration of inappropriate exogenous amino acids in decompensated metabolic septic patients may bring about more harm than benefit, and in septic patients that the levels of serum phenylalanine and proline are elevated persistently along with the decrease of arginine level is a useful prognostic indication.
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PMID:[Changes in serum amino acids in total parenteral nutrition supported patients with intra abdominal infection]. 251 49

Plasma aminogram changes were prospectively studied in 95 patients with external enteric fistula and intraabdominal infection who were under total parenteral nutrition (TPN) therapy with anfuming 14s. Plasma amino acids and albumin were determined before the administration of TPN, weekly and at the end of the therapy or 2 to 5 days before death of patients. In patients with sepsis and starvation, the aminogram showed remarkably low total free amino acids before TPN therapy. In survivors, free amino acids increased gradually to normal in 2 weeks after use of TPN and in the dead increased rapidly to a significantly high peak at the terminal stage. In both survivors and deceased, phenylalanine level remained high during the study. In response to infection, proline was also elevated but to a lesser degree; the ratio of branched chain amino acid (BCAA) to aromatic amino acid (AAA) was lower than normal and the decrease of arginine was parallel to the severity of infection. We conclude that the ideal amino acid preparation for the starved, septic patients should be high in BCAA and arginine but low in phenylalanine; the administration of inappropriate exogenous amino acids in metabolically decompensated septic patients may bring about more harm than benefit; and in septic patients the persistently elevated level of plasma phenylalanine and proline along with decrease of arginine is a useful prognostic sign.
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PMID:Changes of plasma amino acids in total parenteral nutrition-supported patients with intraabdominal infection. 251 37


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