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)

Neuroblastoma cells were synchronized by a combined isoleucine plus glutamine starvation. Adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] was measured under basal conditions and in the presence of dopamine, adenosine and prostaglandin (PG) E1. A clear dissociation occurred between the respective evolution patterns of basal and agonist-stimulated adenylate cyclase activities. The magnitudes of the enzyme response to PGE1, adenosine, and dopamine also exhibited different evolution patterns during the cell cycle. Evolution of adenylate cyclase responsiveness to PGE1 during the cell cycle exhibited striking similarities with the intracellular 3':5'-cyclic AMP changes observed elsewhere. Use of theophylline and fluphenazine as specific inhibitors of adenosine and dopamine, respectively, made it possible to demonstrate that adenosine, dopamine, and PGE1 stimulated adenylate cyclase through independent receptor sites. Furthermore, whatever the stage of the cell cycle, responses to these three agonists were not additive, indicating that the receptors of adenosine, dopamine, and PGE1 control the same adenylate cyclase moieties. The data suggest that adenylate cyclase cell content and enzyme responsiveness to specific agonists can be independently controlled.
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PMID:Adenylate cyclase from synchronized neuroblastoma cells: responsiveness to prostaglandin E1, adenosine, and dopamine during the cell cycle. 26 97

The intracellular concentrations of the adenine nucleotides were determined in suspension cultures of WRL-10A cells, a subline of the L-929 mouse fibroblasts, during the progression of the cells from exponential growth to high-density, nonproliferating populations. The development of the nonproliferating state was associated with a 50% reduction of the adenine nucleotide pool, whereas the energy charge remained at values above 0.90. This change was also observed in the early phase of starvation of low-density cultures and could be reproduced by selective simultaneous withdrawal of glucose and glutamine, which indicated interference with the de novo synthesis of purines. In this respect, therefore, nonproliferating populations of WRL-10A cells resemble purine-limited bacterial systems but not density-inhibited normal fibroblasts in which the size of the adenine nucleotide pool is known to remain unchanged. This difference in the physiologic state of nonproliferating normal and neoplastic cells is potentially significant for tumor chemotherapy.
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PMID:Nonproliferating neoplastic cells in culture: behavior of the adenine nucleotides. 28 95

HS3, a highly phosphorylated dinucleoside originally purified from the fungus Achlya, has been isolated from Chinese hamster ovary cells undergoing glutamine starvation. The HS3 compounds obtained from the fungal and mammalian sources exhibited similar physical and chemical properties. This unusual dinucleotide may be an important regulator of eucaryotic ribonucleoside diphosphate reductase activity; for 50 micrometer HS3, isolated from either mammalian or fungal cells, significantly inhibited CDP reduction in Achlya or hamster cell preparations, but only marginally affected the activity of the enzyme from E. coli. Studies with HS3 isolated from Achlya and partially purified mammalian ribonucleotide reductase indicated that the compound noncompetitively inhibited the reduction of varying concentrations of the substrates CDP, ADP and GDP with Ki values of 23 micrometer, 14 micron and 16 micron respectively. These inhibitor concentrations are well below the estimated intracellular levels of HS3 in glutamine starved cells and suggest that HS3 inhibition of ribonucleotide reduction may be responsible for the rapid inhibition of DNA synthesis seen under these culture conditions.
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PMID:Inhibition of mammalian ribonucleotide reductase by a dinucleotide produced in eucaryotic cells. 33 19

The rate of de novo purine biosynthesis was measured in a series of hypoxanthine guanine phosphoribosyl transferase deficient (HGPRT-) cells from a variety of sources, including human Lesch-Nyhan cells. Under optimum growth conditions, no enhanced purine biosynthesis was detected (in contrast to previous reports). An 'elevated' level of de novo purine biosynthesis could be detected in mutants following starvation for glutamine. However, this was the result of depression of purine biosynthesis in normal cells, with a resulting artifactual overproduction in mutants.
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PMID:Lack of enhanced purine biosynthesis in HGPRT- and Lesch-Nyhan cells. 46 79

Venous plasma and urine amino acids and urea were measured in ten well-trained men, aged 23--45 years, in connection with a 70 km cross-country ski race, lasting 4.39--6.04 h, leading to slight dehydration. The estimated urea production rate during the race was of the order 7.6 mumol/min, kg b.wt, i.e. twice the rate for such men on ordinary protein intake, during ordinary activity, thus suggesting increased protein catabolism. The race led to a fall of the total plasma amino acid concentration to about 60% of the pre-race level. In particular, the branched chain amino acids (valine, iso-leucine, leucine) and alanine were markedly reduced, whereas the S-containing amino acids (taurine, cystine, methionine) and the aromatic (phenylalanine, tyrosine, trytophan, histidine) and glutamine/glutamate were increased, unchanged or only moderately reduced. It is concluded that prolonged heavy exercise is accompanied by increased protein catabolism and changes in the plasma amino acid concentrations similar to those observed during prolonged starvation, but differing from those seen at heavy exercise of less than 2 h duration or prolonged exercise of moderate intensity.
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PMID:Changes in plasma amino acid distribution and urine amino acids excretion during prolonged heavy exercise. 52 87

When guinea-pig lymph node cells were exposed to ConA in a culture medium lacking glutamine or cysteine, no DNA synthesis occurred. The addition of the missing acid to ConA-treated lymphocytes submitted to glutamine or cysteine starvation for 40 h allowed the synthesis of DNA to take place after a period of only 10-12 h. The synthesis of DNA is preceded by a rapid increase of 3H-uridine incorporation into RNA and of 3H-leucine incorporation into protein which occurred a few hours after addition of the missing amino acid. When cycloheximide was added to lymphocytes exposed to ConA in a glutamine or cysteine deprived medium, a relative enhancement of uridine incorporation was observed. No such effect was provoked by puromycin. These results suggest the possibility of a control system in lymphocytes similar to those described in microbial cells for amino acid control of RNA synthesis.
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PMID:Influence on certain amino acids on steps leading to DNA synthesis in concanavalin A-treated guinea-pig lymphocytes. 59 38

In vitro studies have suggested that catabolism of branched chain amino acids is linked with alanine and glutamine formed in, and released from, muscle. To explore this possibility in vivo, static and kinetic studies were performed in three patients with classical, and one patient with partial, branched chain alpha-ketoacid decarboxylase deficiency (maple syrup urine disease, MSUD) and compared to similar studies in eight age-matched controls. The subjects underwent a 24-30-h fast, and a glucose-alanine flux study using stable isotopes. Basal plasma leucine concentrations were elevated (P <0.001) in patients with MSUD (1,140+/-125 muM vs. 155+/-18 muM in controls); and in contrast to the controls, branched chain amino acid concentrations in plasma increased during the fast in the MSUD patients. Basal plasma alanine concentrations were lower (P <0.01) in patients with classical MSUD (153+/-8 muM vs. 495+/-27 muM in controls). This discrepancy was maintained throughout the fast despite a decrease in alanine concentrations in both groups. Plasma alanine and leucine concentrations in the patient with partial MSUD were intermediate between those of the controls and the subjects with the classical form of the disease. Circulating ketone bodies and glucoregulatory hormones concentrations were similar in the MSUD and normal subjects during the fast. Alanine flux rates in two patients with classical MSUD (3.76 and 4.00 mumol/Kg per min) and the patient with partial MSUD (5.76 mumol/Kg per min) were clearly lower than those of the controls (11.72+/-2.53 [SD] mumol/Kg per min). After short-term starvation, glucose flux and fasting concentrations were similar in the MSUD patients and normal subjects.These data indicate that branched chain amino acid catabolism is an important rate limiting event for alanine production in vivo.
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PMID:Glucose and alanine metabolism in children with maple syrup urine disease. 67 Apr

The amino acid pattern following total hip replacement is characterized by increases in muscle of the branched chain amino acids (leucine, isoleucine and valine), the aromatics (phenylalanine and tyrosine) as well as methionine. The nonessential amino acids in muscle tend to decline, glutamine having the most marked change. Plasma levels of the essential amino acids increase while the nonessentials tend to decrease. This pattern differs from that observed in other catabolic states (uremia, starvation, untreated diabetes) and is significantly different from the effects of inactivity and starvation combined. This suggests that injury can be characterized by a unique pattern of muscle and plasma amino acids.
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PMID:Muscle and plasma amino acids after injury: the role of inactivity. 73 57

1. Neither alloxan-diabetes nor starvation affected the rate of glucose production in hepatocytes incubated with lactate, pyruvate, propionate or fructose as substrates. In contrast, glucose synthesis with either alanine or glutamine was increased nearly 3- and 12-fold respectively, in comparison with that in fed rabbits. 2. The addition of amino-oxyacetate resulted in about a 50% decrease in glucose formation from lactate in hepatocytes isolated from fed, alloxan-diabetic and starved rats, suggesting that both mitochondrial and cytosolic forms of rabbit phosphoenolpyruvate carboxykinase function actively during gluconeogenesis. 3. Alloxan-diabetes resulted in about 2-3-fold stimulation of urea production from either amino acid studied or NH4Cl as NH3 donor, whereas starvation caused a significant increase in the rate of ureogenesis only in the presence of alanine as the source of NH3. 4. As concluded from changes in the [3-hydroxybutyrate]/[acetoacetate] ratio, in hepatocytes from diabetic animals the mitochondrial redox state was shifted toward oxidation in comparison with that observed in liver cells isolated from fed rabbits.
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PMID:Effect of alloxan-diabetes on gluconeogenesis and ureogenesis in isolated rabbit liver cells. 74 58

A system for in situ perfusion of rat hindquarters using a fluorocarbon for oxygen and CO2 exchange, and a polyol to provide oncotic pressure is described. Perfusion with glucose plus insulin resulted in no significant change in the tissue level of citrate cycle intermediates, phosphocreatine, ATP, ADP, AMP, and glycogen. Glucose was consumed at a linear rate, and lactate, pyruvate, alanine, glutamine, glutamate, and citrate were released into the perfusing medium. Inclusion of pyruvate resulted in elevation of citrate cycle intermediates and alanine, whereas acetate elevated the level of cycle intermediates without significant effect on tissue alanine or its release. Radioactivity from NaH[14C]O3 was incorporated into citrate cycle intermediates, glutamate, aspartate, and lactate by glucose-perfused hindquarters, the extent of which was markedly elevated as the tissue pyruvate was increased. When pyruvate was in the physiological range, acetate caused elevation in incorporation of CO2 into these metabolites, increased the concentration of citrate, and doubled the concentration of acetyl-CoA. Thirty-five to forty-four per cent of 14C incorporated into citrate was retained after enzymic degradation to 2-oxoglutarate. Perfusion with [2-14C-]propionate led to elevation in the level of citrate cycle intermediates, and radioactivity was incorporated into the latter, as well as glutamate, aspartate, lactate, pyruvate, alanine, and CO2. Two independent calculations estimated the rate of flux of 4-carbon cycle intermediates to 3-carbon metabolites of about 68 mumol/h (approximately 38 nmol/min/g of tissue), a rate in excess of those reported for alanine release from human or rat muscle during starvation. Arsenite blocked carbohydrate flux through the citrate cycle and effected accumulation of lactate, pyruvate, alanine, and 2-oxoglutarate. Flux from 4- to 3-carbon acids was diminished by arsenite, apparently as a result of lowered substrate concentration for decarboxylation. 3-Mercaptopicolinic acid, an inhibitor of phosphoenolpyruvate carboxykinase, was without effect on the parameters studied, suggesting that this enzyme is not involved in the decarboxylation reaction. It is concluded that (a) a constant level of citrate cycle intermediates is maintained in part by continuous flux of carbon into and out of the cycle by carboxylation and decarboxylation reactions; (b) the carbon skeleton of alanine released from skeletal muscle is derived in part from other amino acids which are catabolized to cycle intermediates; and (c) the subsequent removal of these intermediates is probably mediated by malic enzyme(s) (EC 1.1.1.40, or 1.1.1.36, or both.
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PMID:Carboxylation and decarboxylation reactions. Anaplerotic flux and removal of citrate cycle intermediates in skeletal muscle. 76 69


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