Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic fatigue is a characteristic muscle response to intense exercise that has outstripped the rate of ATP replacement. The accumulation of metabolic by-products, namely hydrogen ions and diprotonated phosphate, interferes with actin-myosin interaction, effectively preserving muscle ATP levels by preventing further ATP hydrolysis. Muscle force and metabolite concentrations return to normal in about 5 minutes. Less intense exercise causes a more subtle, non-metabolic fatigue due to a still-undefined disturbance of excitation-contraction coupling, which can last for several hours. In this type of fatigue, greater effort is required to generate submaximal forces. Endurance exercise is mainly limited by the size of muscle glycogen stores and how efficiently they are used. Endurance training permits an athlete to work aerobically at high rates, consuming a mixture of lipid and carbohydrate fuels. When muscle glycogen is used up, exercise can only continue at the relatively low rate supportable by lipid metabolism. Anaerobic exercise is also limited by subjective factors such as dyspnoea and muscle pain, which have objective determinants. Extremely prolonged exercise can lead to general collapse because of dehydration, hyperthermia, or hypoglycaemia. None of these factors explains the phenomenon of asthenia, a subjective sense of exhaustion that produces no objective impairment of physical performance. The metabolic myopathies are experiments of nature that promise to shed new light on the biochemical basis of muscle fatigue. This will require quantitative studies of the kind provided by topical magnetic resonance spectroscopy, correlating physiology and metabolism in vivo.
 ...
PMID:Muscle metabolism during fatigue and work. 226 24

The fluorescent dye 10-N-nonyl acridine orange (NAO), known as specifically associated with mitochondria, has been reported to have a cytotoxic effect when high doses were applied to cells. Presently, the biochemical basis of its toxicity was investigated on isolated rat liver mitochondria. At low concentrations, NAO strongly inhibited state 3 respiration and ATP synthesis. At high concentrations, electron transport, ATP hydrolysis, Pi-transport and adenine nucleotide activities were also decreased. All these inhibitions can be explained by probe-cardiolipin interactions which could induce the collapse of energy conversion and/or the modification of membrane fluidity.
 ...
PMID:Specific interaction of the new fluorescent dye 10-N-nonyl acridine orange with inner mitochondrial membrane. A lipid-mediated inhibition of oxidative phosphorylation. 229 1

The quantitative importance of glycolysis in cardiomyocyte reenergization and contractile recovery was examined in postischemic, preload-controlled, isolated working guinea pig hearts. A 25-min global but low-flow ischemia with concurrent norepinephrine infusion to exhaust cellular glycogen stores was followed by a 15-min reperfusion. With 5 mM pyruvate as sole reperfusion substrate, severe contractile failure developed despite normal sarcolemmal pyruvate transport rate and high intracellular pyruvate concentrations near 2 mM. Reperfusion dysfunction was characterized by a low cytosolic phosphorylation potential [( ATP]/[( ADP][Pi]) due to accumulations of inorganic phosphate (Pi) and lactate. In contrast, with 5 mM glucose plus pyruvate as substrates, but not with glucose as sole substrate, reperfusion phosphorylation potential and function recovered to near normal. During the critical ischemia-reperfusion transition at 30 s reperfusion the cytosolic creatine kinase appeared displaced from equilibrium, regardless of the substrate supply. When under these conditions glucose and pyruvate were coinfused, glycolytic flux was near maximum, the glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase reaction was enhanced, accumulation of Pi was attenuated, ATP content was slightly increased, and adenosine release was low. Thus, glucose prevented deterioration of the phosphorylation potential to levels incompatible with reperfusion recovery. Immediate energetic support due to maximum glycolytic ATP production and enhancement of the glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase reaction appeared to act in concert to prevent detrimental collapse of [ATP]/[( ADP][Pi]) during creatine kinase dysfunction in the ischemia-reperfusion transition. Dichloroacetate (2 mM) plus glucose stimulated glycolysis but failed fully to reenergize the reperfused heart; conversely, 10 mM 2-deoxyglucose plus pyruvate inhibited glycolysis and produced virtually instantaneous de-energization during reperfusion. The following conclusions were reached. (1) A functional glycolysis is required to prevent energetic and contractile collapse of the low-flow ischemic or reperfused heart (2). Glucose stabilization of energetics in pyruvate-perfused hearts is due in part to intensification of glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase activity. (3) 2-Deoxyglucose depletes the glyceraldehyde-3-phosphate pool and effects intracellular phosphate fixation in the form of 2-deoxyglucose 6-phosphate, but the cytosolic phosphorylation potential is not increased and reperfusion failure occurs instantly. (4) Consistent correlations exist between cytosolic ATP phosphorylation potential and reperfusion contractile function. The findings depict glycolysis as a highly adaptive emergency mechanism which can prevent deleterious myocyte deenergization during forced ischemia-reperfusion transitions in presence of excess oxidative substrate.
 ...
PMID:Glucose requirement for postischemic recovery of perfused working heart. 231 14

Vitreoscilla is a Gram-negative bacterium with unique respiratory physiology in which Na+ was implicated as a coupling cation for the generation of a transmembrane electrical gradient (delta psi). Thus, cells respiring in the presence of 110 mM Na+ generated a delta psi of -142 mV compared to only -42 and -56 mV for Li+ and choline, respectively, and even the -42 and -56 mV were insensitive to the protonophore 3,5-di-tert-butyl-4-hydroxybenzaldehyde (DTHB). The kinetics of delta psi formation and collapse correlated well with the kinetics of Na+ fluxes but not with those of H+ fluxes. Cyanide inhibited respiration, Na+ extrusion, and delta psi formation 81% or more, indicating that delta psi formation and Na+ extrusion were coupled to respiration. Experiments were performed to distinguish among three possible transport systems for this coupling: (1) a Na(+)-transporting ATPase; (2) an electrogenic Na+/H+ antiport system; (3) a primary Na+ pump directly driven by the free energy of electron transport. DCCD and arsenate decreased cellular ATP up to 86% but had no effect on delta psi, evidence against a Na(+)-transporting ATPase. Low concentrations of DTHB had no effect on delta psi; high concentrations transiently collapsed delta psi, but led to a stimulation of Na+ extrusion, the opposite of that expected for a Na+/H+ antiport system. Potassium ion, which collapses delta psi, also stimulated Na+ extrusion. The experimental evidence is against Na+ extrusion by mechanisms 1 and 2 and supports the existence of a respiratory-driven primary Na+ pump for generating delta psi in Vitreoscilla.
 ...
PMID:Respiratory-driven Na+ electrical potential in the bacterium Vitreoscilla. 237 55

Correlations were made among ATP synthesis, transmembrane K+ gradients, and leakage of three amino acid neurotransmitters, gamma-aminobutyric acid (GABA), aspartate, and glutamate, in rat brain synaptosomes incubated under normoxic and respiration-limited conditions. Even under normoxic conditions, a substantial proportion of total ATP synthesis (8%) was provided by glycolysis. Limitation of respiration by approximately 30% through addition of amobarbital (Amytal) caused a twofold decrease in the creatine phosphate/creatine ([CrP]/[Cr]) ratio, and consequently the [ATP]/[ADP] ratio, and a threefold increase in lactate production. There was a detectable decrease in intracellular [K+] and small rises in external GABA, aspartate, and glutamate concentrations. More severe limitations in ATP synthesis caused larger declines in the [CrP]/[Cr] ratio and progressive leakage of K+ and neurotransmitter amino acids. A comparison of delta GATP and delta GNa, K showed the former to be larger by 6 kcal, which indicates that the plasma membrane Na+/K+ pump operates at far from equilibrium. Under respiration-limited conditions, even when total ATP synthesis decreased by approximately 80% and [ATP] declined to less than 0.4 mM, delta GATP was still larger than delta GNa,K. It is suggested that during hypoxia and ischemia, the activity of the plasma membrane Na+/K+ pump in brain becomes limited by [ATP], which falls below the Km value for the low-affinity regulatory site on the enzyme. This failure of the pump and consequent collapse of the ion gradients may contribute to the leakage of neurotransmitter amino acids that occurs in these pathological states.
 ...
PMID:Relationships among ATP synthesis, K+ gradients, and neurotransmitter amino acid levels in isolated rat brain synaptosomes. 244 8

The nucleoside analog 3'-deoxyadenosine (cordycepin) rapidly collapses the intermediate filaments into juxtanuclear caps in interphase fibroblasts and keratinocytes. A minimum of 80 micrograms/ml cordycepin or 20 micrograms/ml cordycepin in combination with 2 micrograms/ml of the deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenosine (EHNA) to inhibit its degradation is required to see these effects. This is the same concentration required for cordycepin to arrest cells at the onset of mitosis and depolymerize the microtubules to small asters. Cordycepin enters the cells rapidly and is phosphorylated to 3'-dATP with a concomitant drop in ATP levels. However, the direct reduction of ATP levels does not mimic the same rapid effects of cordycepin on either the intermediate filaments or microtubules. In addition, similar effects are not produced by a variety of other adenosine analogs with alterations in the 2'- and 3'-ribose positions. Although other pharmacological reagents result in alterations of the fibroblastic intermediate filaments, cordycepin is unusual because of the rapidity with which the fibroblastic intermediate filaments collapse into the juxtanuclear caps. The juxtanuclear caps have a morphology different from that of the perinuclear bundles of intermediate filaments that arise after long-term depolymerization of the microtubules. The keratin fibers in the epidermal cells retract to a perinuclear ring when treated with cordycepin.
 ...
PMID:Cordycepin rapidly collapses the intermediate filament networks into juxtanuclear caps in fibroblasts and epidermal cells. 245 49

Chlorotriethylphosphine gold(I) (TEPAu) is an organo-gold compound that has therapeutic activity in animal models of rheumatoid arthritis. Initial studies have suggested that TEPAu is a potent cytotoxic compound in vitro against a variety of cultured cell types and isolated hepatocytes. Mitochondrial dysfunction induced by this compound has been suggested as a primary biochemical alteration which may result in lethal cell injury in isolated hepatocytes. The purpose of this study was, therefore, to determine the mechanism of TEPAu-induced dysfunction of isolated rat liver mitochondria. TEPAu induced a rapid, concentration-related collapse of the mitochondrial inner membrane potential (EC50 = 24.7 +/- 2.5 microM) which was potentiated in Ca2+ loaded mitochondria (EC50 = 11.3 +/- 3.8 microM). TEPAu-induced collapse of the membrane potential was partially inhibited in the presence of ruthenium red or EGTA. TEPAu caused the rapid release of mitochondrially sequestered Ca2+ which was not inhibited by ruthenium red and, thus, was not via a reversal of the Ca2+ uniporter. TEPAu caused mitochondrial swelling, increased permeability of the inner membrane, and the oxidation/hydrolysis of endogenous mitochondrial pyridine nucleotides. Addition of exogenous ATP slightly reversed the effects of TEPAu on pyridine nucleotides. TEPAu-induced mitochondrial alterations were reversed or inhibited by exposure to the sulfhydryl reducing agent, dithiothreitol. Also, the TEPAu-induced collapse of the mitochondrial membrane potential was partially inhibited by dibucaine, a non-specific inhibitor of phospholipases. These data suggest that TEPAu-induced mitochondrial dysfunction is sulfhydryl dependent. TEPAu-induced mitochondrial dysfunction results in dissipation of the potential difference across the inner mitochondrial membrane which inhibits mitochondrial oxidative phosphorylation. The mechanism by which TEPAu induces the collapse of the membrane potential may be mediated by a sulfhydryl-dependent increase in permeability of the inner membrane to protons.
 ...
PMID:The mechanism of acute cytotoxicity of triethylphosphine gold(I) complexes. III. Chlorotriethylphosphine gold(I)-induced alterations in isolated rat liver mitochondrial function. 247 Dec 92

To determine the possible role of acidic lysosomal vesicles in the transcellular transport of Ca, bidirectional Ca fluxes were measured across intestinal segments in vitro in the absence of electrochemical gradients. Mucosal addition of the weak base quinacrine (0.2 mM) caused a 67% decline in the mucosal-to-serosal Ca flux (Jm----s) across duodenum (175 +/- 34 vs. 58 +/- 9 nmol.cm-2.h-1, P less than 0.007) and reduced cecal Ca Jm----s (177 +/- 15 vs. 45 +/- 4, P less than 0.0001). Higher concentrations of up to 2.0 mM caused no further decline in cecal Ca Jm----s. Inhibition of cecal Ca Jm----s by mucosal chloroquine (0.1 mM) or ammonium chloride (10 mM) varied from 37 to 50%. Addition in vitro of quinacrine to enterocyte basolateral membrane vesicles failed to inhibit ATP-dependent Ca uptake. The present studies demonstrate that agents that collapse lysosomal pH gradients inhibit transcellular Ca transport. These observations are consistent with the hypothesis that Ca destined for transcellular transport is functionally associated with acidic lysosomes and that these organelles play an important role in transepithelial Ca translocation.
 ...
PMID:Effects of quinacrine on calcium active transport by rat intestinal epithelium. 259 12

Isolated rat hepatocytes were incubated with ATP to induce high intracellular free Ca2+ concentrations as determined with the Quin-2 method. Immediately after addition of ATP, the intracellular concentration of Ca2+ rose from 200 nM to more than 2.5 microM. It stayed at this value during the first 1/2 h; the rise was absolutely dependent on extracellular Ca2+. After the first 1/2 h the Ca2+ concentration decreased to 1-2 microM (5-10 times the control value). These high intracellular free Ca2+ concentrations did not lead to an immediate loss of cell viability. Only after 2 h of incubation a substantial number of cells lost viability. This was preceded by a decrease in cellular NADH (greater than 40%) and accompanied by a sharp increase in the intracellular Ca2+ concentration. Under these conditions the NADPH concentration was not affected. Cellular GSH was decreased to 30% of the initial value, but no lipid peroxidation or protein-thiol depletion was observed. Intracellular ATP, ADP and AMP were increased in the presence of extracellular ATP. Ca2+-dependent proteases seemed not to be involved in cell death. These observations are consistent with a collapse of mitochondrial functions as a final trigger of cell death.
 ...
PMID:Prolonged high intracellular free calcium concentrations induced by ATP are not immediately cytotoxic in isolated rat hepatocytes. Changes in biochemical parameters implicated in cell toxicity. 259 7

The efficiency of 31P homonuclear decoupling in vivo is demonstrated. In low-field clinical situations, when JPP is equal to or greater than delta v, significant improvements in the precision of measuring the ATP resonance area can be expected upon decoupling due to the increase in signal-to-noise produced upon collapse of the J coupling. The sensitivity loss due to time sharing between the decoupler and receiver is discussed.
 ...
PMID:Improvement in 31P NMR signal-to-noise for ATP in vivo using homonuclear decoupling. 261 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>