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

Endogenous excretion of nitrogenous products was studied during early starvation in six healthy, nonobese subjects after six days on a well-defined diet, designed to achieve net protein balance and an adequate calorie supply. The diet contained 0.5 g myofibrillar-free protein and 35 kcal/kg body weight. The subjects then fasted for three days. Urine was collected for 24-hour periods and analyzed for urea, ammonia, 3-methylhistidine, and 1-methylhistidine. Blood glucose and serum urea levels were measured daily. In a second group of subjects, muscle biopsies for determination of free amino acid concentrations were taken in the overnight fasted state and after three days of fasting. During the period with a balanced diet, urea production fell initially and stabilized after two to three days at a level of 146 +/- 15 mmol/24 h. During the period of fasting, serum urea increased from 3.0 +/- 0.4 to a maximum value of 6.2 +/- 0.7 mmol/L and urea production rose markedly, to a peak of 293 +/- 16 mmol/24 h. Ammonia excretion was 24 +/- 2 mmol/24 h before and 71 +/- 13 mmol/24 h after three days of fasting. 3-Methylhistidine excretion was stable before fasting and then rose from 154 +/- 17 to 198 +/- 17 mumol/24 h. 1-Methylhistidine excretion was unchanged during fasting. Blood glucose levels were stable at 4.8 +/- 0.2 mmol/L before fasting and then fell to 3.7 +/- 0.3 mmol/L. Intracellular concentrations of amino acids in skeletal muscle decreased markedly during fasting; after three days of fasting the glutamine concentration had fallen by 34%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein and amino acid metabolism during early starvation as reflected by excretion of urea and methylhistidines. 259 32

Periplasmic permeases are composed of four proteins, one of which has an ATP-binding site that has been postulated to be involved in energy coupling. Previous data suggested that these permeases derive energy from substrate level phosphorylation (Berger, E. A. (1973) Proc. Natl. Acad. Sci. U.S.A. 70, 1514-1518); however, conflicting results later cast doubt upon this hypothesis. Here, we make use of two well characterized periplasmic permeases and of a well characterized unc mutant (ATPase-) to examine this energetics problem in depth. We have utilized the histidine and maltose periplasmic permeases in Escherichia coli as model systems. Isogenic unc strains were used in order to study separately the effect of the proton-motive force and of ATP on transport. These parameters were analyzed concomitantly with transport assays. Starvation experiments indicate that both histidine and maltose transport require ATP generation and that a normal level of delta psi is not sufficient. Uncouplers such as carbonyl cyanide-m-chlorophenylhydrazone and 2,4-dinitrophenol dissipated the delta psi without decreasing the ATP level and without significant effect on these permeases, showing that delta psi is not needed. Inhibition of ATP synthesis by arsenate eliminates transport through both permeases, confirming the need for ATP. In agreement with previous results with the glutamine permease (Plate, C. A. (1979) J. Bacteriol. 137, 221-225), valinomycin plus K+ dissipates delta psi without affecting ATP levels and inhibits histidine transport; however, maltose transport is not inhibited under these conditions. This result is discussed in terms of the artefactual side effects caused by valinomycin/K+ treatment on some periplasmic permeases. Histidine transport is also shown to be sensitive to changes in the cytoplasmic pH. It is concluded that periplasmic permeases indeed have an obligatory requirement for ATP (or a closely related molecule), whereas the proton-motive force is neither sufficient nor essential.
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PMID:Energy coupling in bacterial periplasmic transport systems. Studies in intact Escherichia coli cells. 264 55

This article reviews work we have carried out to investigate (1) the transport mechanisms responsible for the high distribution ratio of free glutamine commonly observed in skeletal muscle; (2) the fall in the distribution ratio that accompanies starvation, injury and chronic disease, whether directly involving muscle or not; and (3) the effect of modulation of intracellular free-glutamine concentration on protein synthesis and breakdown in skeletal muscle. We suggest that the results are consistent with the controlling role of the muscle membrane glutamine-sodium cotransporter in the regulation of the intracellular glutamine pool, the existence of pathophysiological mechanisms for the modulation of intramuscular glutamine and anabolic effects of glutamine in promoting protein synthesis, with a smaller effect in reducing protein breakdown. The mechanisms by which glutamine affects skeletal muscle protein turnover, and thus muscle protein balance, and the extent of the net flow of amino acids between the periphery and the viscera are unknown as yet, but the results suggest that modulation of transporter activity may offer the possibility of therapeutic intervention to reduce muscle wasting associated with injury and disease.
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PMID:Skeletal muscle glutamine transport, intramuscular glutamine concentration, and muscle-protein turnover. 266 3

A comparison of the changes in the concentration of glutamine [Gln] in skeletal muscle in a variety of catabolic states with the attendant changes in rates of protein synthesis and degradation indicates a number of substantial correlations which provide insight into both the way in which [Gln] is regulated in muscle and possible regulatory influences of [Gln] on protein balance. There is a striking direct correlation between [Gln] and the rate of protein synthesis in the whole data set. Further examination of this relationship in protein deficiency shows that the changes in [Gln] correlate mainly with the reductions in ribosomal concentration (RNA/protein) and with the decrease in the rate of protein degradation. Because the fall in [Gln] in protein deficiency is also correlated with the decrease in free T3 concentrations, it is suggested that in this case the correlations of [Gln] with rates of protein turnover may be incidental, reflecting thyroidal influences on both protein turnover and glutamine transport. In contrast, in endotoxemia the changes in [Gln] were highly correlated with the ribosomal activity, kRNA, and in this case [Gln] was inversely correlated with the rate of protein degradation. Similar correlated changes occur in starvation and in response to glucocorticoids, and it is suggested that the reductions in [Gln] in endotoxemia could be causally related to the development of insulin resistance and the inhibition of the translational phase of protein synthesis which occurs in these circumstances. The mechanism of the reduction in [Gln] and any linked inhibition of protein synthesis is unknown, but it is shown to be independent of prostaglandin production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscle glutamine concentration and protein turnover in vivo in malnutrition and in endotoxemia. 266 4

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

The colonic mucosa may be especially vulnerable during starvation and malnutrition, as luminal nutrients make the greatest contribution to its energy production. To investigate possible metabolic changes in the colonic mucosa during nutrient restriction, we studied substrate utilization by colonocytes isolated from three groups of 6-wk-old rats: control, fasted (72 h), and chronically malnourished animals. Isolated colonocytes were incubated with nonlabeled and 14C-labeled substrates (glucose, glutamine, n-butyrate, or beta-hydroxybutyrate). Substrate oxidation and net increase of intermediary metabolites were reduced in fasted and malnourished animals. The effect of fasting on substrate oxidation was greater than that of chronic malnutrition for all substrates tested except n-butyrate. The total ketone body concentrations and beta-hydroxybutyrate to acetoacetate ratios were higher in the fasted and malnourished groups than in controls. The findings suggest that the colonic mucosa responds to nutrient deprivation by a general reduction of oxidative metabolism that is associated with an altered redox state.
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PMID:Isolated colonocyte metabolism of glucose, glutamine, n-butyrate, and beta-hydroxybutyrate in malnutrition. 275 23

The effect of 36-hour starvation on the net uptake/release of amino acids and glucose by interscapular brown adipose tissue (IBAT) of the rat has been studied by means of the determination of the arterio-venous differences in their blood concentrations. Starvation induced a net release of non-essential amino acids by the tissue, mainly alanine, glutamine, glycine and citrulline. In food deprived animals there was not a net glucose uptake by the IBAT. The results obtained in this study are in accordance with a typical peripheral tissue metabolic pattern of IBAT under food deprivation situations.
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PMID:Effect of 36-hour starvation on in vivo amino acid and glucose uptake by rat brown adipose tissue. 278 46

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

The state of adenylylation, n, of glutamine synthetase (GS) in Pseudomonas fluorescens has been determined as a function of growth conditions. Compared to the behavior of Escherichia coli, atypical responses to either carbon or nitrogen starvation were observed when P. fluorescens was grown with either succinate, malate, or fumarate as the sole source of carbon and energy. Under conditions of carbon starvation (high NH4+, low dicarboxylic acid substrate), the value of n falls rapidly from 10 to 1.0 during prolonged incubation in the stationary phase, whereas the value of n is unexpectedly high (ca. 10) in extracts of nitrogen-starved cells. These abnormal responses are attributable to particular permeability properties of P. fluorescens cells compared to E. coli. The unusual changes in nitrogen-starved cells are related to the release of alpha-ketoglutarate by such cells during incubation or washing procedures. These changes can be prevented by the addition of cetyltrimethylammonium bromide (CTAB) to the cultures 5 min prior to harvesting the cells, or by freezing the cell pellets just after centrifugation and sonication within 3 min of suspension in buffer, or by suspending freshly harvested cells in buffer containing alpha-ketoglutarate and orthophosphate (i.e., effectors that favor deadenylylation of glutamine synthetase). The abnormal changes which occur during carbon starvation in the presence of excess NH4+ can be prevented by addition of ATP and glutamine to the buffer in which the freshly harvested cells are suspended prior to sonication. The results suggest that during the stationary phase of growth on succinate, fumarate, or malate (but not on glucose), the cellular membrane becomes permeable to small molecules that regulate the adenylylation cascade, and indeed, it was observed that such whole cells expressed, without any chemical or physical treatment, more than 50% of the glutamine synthetase activity they contained. Such cells may be useful in studies to examine the effects of multiple metabolites on the regulation of glutamine synthetase adenylylation in situ.
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PMID:Adenylylation state of glutamine synthetase and permeability properties of Pseudomonas fluorescens. 287 12

The activities of alanine and aspartate transaminases, adenylate deaminase, glutamine synthetase and glutamate and xanthine dehydrogenases have been measured in liver, yolk sac membrane, intestine and breast and leg muscle of domestic fowl hatchlings receiving for 3 or 5 days either a standard diet or hard boiled eggwhite as well as in 3 or 5 days starved animals. The patterns of activation of amino acid metabolism enzymes were fully comparable in protein-fed and starved groups with respect to fed controls; the differences with respect to the latter became more marked in 5- than in 3-days old chicks. In 5-days old chicks intestine alanine transaminase activity increased in parallel to that of liver in protein-fed animals but not in those starved, in agreement with an enhanced alanine transfer between both organs under this situation. Both, starvation and protein-feeding, induced a general decrease in the amino acid metabolizing ability of muscle. Glutamine (but not alanine) synthetizing capabilities were enhanced.
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PMID:Effect of starvation and a protein diet on the amino acid metabolism enzyme activities of the organs of domestic fowl hatchlings. 287 42


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