Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the effects of preinduced hypothermia on the physiological and thermoregulatory responses to exercise in the heat rats were intravenously administered either 100 micrograms of chlorpromazine (CPZ) or 200 mg/kg of L-tryptophan (L-Trp) under restraint in a cold (4 degrees C) environment. When rectal temperatures (Tre) reached 32-33 degrees C the rats were removed to a hot environment (35 degrees C) where they ran on a level treadmill (9.14 m/min) to hyperthermic exhaustion (Tre, 42.5-43 degrees C). Both CPZ and L-trp hypothermia was effective in increasing significantly (P less than 0.001) the time to hyperthermic exhaustion. However, the maximal Tre and skin temperatures (Tsk) attained were unaffected by either treatment. When the rats exercised on the treadmill, increments (degrees C/min) in Tre and Tsk were significantly (P less than 0.02, minimal) greater for the initially hypothermic animals compared to normothermic controls. Cooling rates were unaffected by either treatment. We concluded from these studies that, although preinduced hypothermia is extremely effective in prolonging the time to hyperthermic exhaustion, no additional beneficial thermoregulatory responses accrued as a result of this treatment.
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PMID:Hypothermia induced by chlorpromazine or L-tryptophan: effects on treadmill performance in the heat. 51 90

In suckling hyperphenylalaninemic (hyper-Phe) rats, all essential amino acids including tryptophan are depleted in the blood. The inadequate supply of Trp to the developing brain leads to a decline of Trp, of serotonin, and of 5-hydroxyindoleacetic acid. The exhaustion of amino acids in both blood and brain can be restored by administration of Lys. Even though Phe is still elevated in blood and brain, Trp, serotonin and 5-hydroxyindoleacetic acid, are no longer depleted in the brain. This observation contradicts the idea that the serotonin deficit in the developing hyper-Phe brain is caused by competitive uptake inhibition of tryptophan or by the interference of Phe metabolites with the formation of serotonin. Increased accumulation of all large neutral amino acids in peripheral tissues and an impeded intestinal amino acid transport in suckling hyper-Phe rats appear to be responsible for the deficient supply of other amino acids, including Trp, to the developing brain. The availability of Lys for developing extraintestinal tissues seems to be involved in the regulation of intestinal amino acid transport.
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PMID:The depletion of tryptophan and serotonin in the brain of developing hyperphenylalaninemic rats is abolished by the additional administration of lysine. 243 75

Phosphorescence of protein tryptophan was analyzed in sarcoplasmic reticulum vesicles, and in the purified Ca2+ transport ATPase in deoxygenated aqueous solutions at room temperature. Upon excitation with light of 295 nm wavelength, the emission maxima of fluorescence and phosphorescence were at 330 nm and at 445 nm, respectively. The phosphorescence decay was multiexponential; the lifetime of the long-lived component of phosphorescence was approximately equal to 22 ms. ATP and vandate significantly reduced the phosphorescence in the presence of either Ca2+ or EGTA; ADP was less effective, while AMP was without effect. The quenching by ATP showed saturation consistent with the idea that the ATP-enzyme complex had a lower phosphorescence yield. Upon exhaustion of ATP, the phosphorescence returned to starting level. Significant quenching of phosphorescence with a decrease in phosphorescence lifetime was also caused by NaNO2, methylvinyl ketone and trichloroacetate, without effect on ATPase activity; this quenching did not show saturation and was therefore probably collisional in nature.
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PMID:Tryptophan phosphorescence of the Ca2+-ATPase of sarcoplasmic reticulum. 297 55

The performance of strenuous physical exercise is associated with discomfort and pain, the tolerance for that being modulated by the activity of the endogenous opioid systems. As 5-hydroxy-tryptamine (5-HT) affects nociception through its effects on the enkephalin-endorphin system, we have analyzed the effects of a moderate supplementation with L-tryptophan, the immediate precursor of 5-HT, on endurance and sensation of effort. Twelve healthy sportsmen were subjected to a work load corresponding to 80% of their maximal oxygen uptake on two separate trials, after receiving a placebo and after receiving the same amount of L-tryptophan. The subjects ran on a treadmill until exhaustion. Total exercise time, perceived exertion rate, maximum heart rate, peak oxygen consumption, pulse recovery rate, and excess post-exercise oxygen consumption were determined during the two trials. The total exercise time was 49.4% greater after receiving L-tryptophan than after receiving the placebo. A lower rate of perceived exertion was exhibited by the group while on tryptophan although the differences from the control group were not statistically significant. No differences were observed in the other parameters between the two trials. The longer exercise time als well at the total work load performed could be due to an increased pain tolerance as a result of L-tryptophan ingestion.
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PMID:Effect of L-tryptophan supplementation on exercise performance. 324 61

When tryptophanyl-tRNA synthetase from Escherichia coli is allowed to react with L-tryptophan and ATP-Mg in the presence of inorganic pyrophosphatase, the fluorescence change of the reaction mixture reveals three or four sequential processes, depending on the buffer used. Quenched-flow and stopped-flow experiments show that the first two processes, which occur in the 0.001-1.0-s time scale, can be correlated to the formation of two moles of tryptophanyl-adenylate per mole of dimeric enzyme. These two processes are reversible by adding PPi, as seen in the fluorimeter. The third process leads to a reaction product that can no longer reform ATP after addition of PPi and that represents tryptophanyl-ATP ester, as demonstrated by thin-layer chromatography. This compound has been previously shown to be formed by tryptophanyl-tRNA synthetase from E. coli [K. H. Muench (1969) Biochemistry 8, 4872-4879]. Its formation is accompanied by a fluorescence decrease which reaches a minimum in about 30 min. The nature of the fourth process depends on the reaction conditions employed. In sodium bicarbonate or potassium phosphate buffer, the fourth process corresponds to the non-enzymatic hydrolysis of tryptophanyl-ATP ester. This spontaneous hydrolysis competes with formation of the ester and limits its concentration. Eventually, the progressive exhaustion of ATP brings the fluorescence intensity of the reaction mixture back to its initial value. In contrast, in ammonium bicarbonate buffer the previous third process is no longer visible, as evidenced by the absence of a fluorescence decrease beyond the fast initial quenching linked to the formation of tryptophanyl-adenylate. Instead, a fluorescence increase is observed. However, unlike the fourth process seen in sodium bicarbonate buffer, the fluorescence increase in ammonium bicarbonate is much larger than the initial fluorescence decrease linked to adenylate formation, the final fluorescence greatly surpassing the starting fluorescence signal. The reaction product of this process is tryptophanamide, as evidenced by high-performance liquid chromatography. Tryptophanamide formation is faster than that of tryptophanyl-ATP ester and is enzyme-catalyzed with a Km of 1 mM for ammonia and a rate constant of 5.7 min-1 at pH 8.3, 25 degrees C. The affinity of tryptophanamide for the protein is too weak to allow the formation of a significant concentration of enzyme-product complex. Tryptophanamide is therefore released in the reaction medium and its concentration reaches that of the limiting substrate.
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PMID:Tryptophanamide formation by Escherichia coli tryptophanyl-tRNA synthetase. 388 Dec 55

1. An increased uptake of tryptophan in the brain may increase serotoninergic activity and recently has been suggested to be a cause of fatigue during prolonged exercise. The present study, therefore, investigates whether ingestion of tryptophan or the competing branched-chain amino acids (BCAAs) affect performance. Ten endurance-trained male athletes were studied during cycle exercise at 70-75% maximal power output, while ingesting, ad random and double-blind, drinks that contained 6% sucrose (control) or 6% sucrose supplemented with (1) tryptophan (3 g l-1), (2) a low dose of BCAA (6 g l-1) or (3) a high dose of BCAA (18 g l-1). 2. These treatments greatly increased the plasma concentration of the respective amino acids. Using the kinetic parameters of transport of human brain capillaries, BCAA supplements were estimated to reduce brain tryptophan uptake at exhaustion by 8-12%, while tryptophan ingestion caused a 7- to 20-fold increase. Exercise time to exhaustion was not different between treatments (122 +/- 3 min). 3. The data suggest that manipulation of tryptophan supply to the brain either has no additional effect upon serotoninergic activity during prolonged exhaustive exercise or that manipulation of serotoninergic activity functionally does not contribute to mechanisms of fatigue.
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PMID:Ingestion of branched-chain amino acids and tryptophan during sustained exercise in man: failure to affect performance. 747 39

SA-FF22 is a lanthionine-containing bacteriocidal peptide isolated from Streptococcus pyogenes strain FF22. The peptide interacts closely with non-energised artificial phospholipid vesicles, as evidenced by a 'blue shift' in the fluorescent emissions associated with a tryptophan residue within the peptide sequence. Furthermore, SA-FF22 induced efflux of radiolabelled amino acids from artificially energised cytoplasmic membrane vesicles and arrested uptake of amino acids by intact cells. By measuring the decrease in membrane potential of both starved and energised SA-FF22-treated cells, and through the use of artificial planar membranes, a potential of approximately 100 mV was deduced as the minimum required to induce pore formation by SA-FF22. This threshold potential is independent of the orientation of the applied voltage (i.e. trans or cis orientations are equally effective). Single channel conductance measurements suggested that the pores formed by SA-FF22 are relatively unstable, short-lived and approximately 0.5-0.6 nm in diameter. This is somewhat smaller than those of the previously described, pore-forming lantibiotics and should not allow significant efflux of large molecules such as ATP. Thus, death of affected cells seems to result from membrane-potential disruption and subsequent exhaustion of the cells.
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PMID:The mode of action of SA-FF22, a lantibiotic isolated from Streptococcus pyogenes strain FF22. 830 35

Tryptophan is the precursor of the neurotransmitter 5-hydroxytryptamine (5-HT), known to be involved in sleep and fatigue. In the blood, tryptophan binds to albumin, and that which does not, free tryptophan, competes with branched chain amino acids (BCAA) for entry into the brain. The plasma concentrations of albumin, free tryptophan, total tryptophan, and BCAA were measured before and after major surgery in nine elderly and nine coronary artery bypass graft (CABG) patients. In both the elderly and the CABG patients plasma free tryptophan concentrations were increased after surgery, compared with baseline levels; the plasma free tryptophan/BCAA concentration ratio was also increased significantly after surgery. Plasma albumin concentrations were decreased significantly after surgery in both the elderly and the CABG patients. Plasma BCAA concentrations were not affected by surgery in either group. The effect of exercising to exhaustion on 5-HT and tryptophan were investigated in Nagase analbuminemic rats (NAR). The intrasynaptosomal concentration of tryptophan, 5-hydroxy-tryptophan, and 5-HT was increased by fatigue after exercise. In addition, running time to exhaustion was shortened in NAR. These data suggest that free tryptophan uptake and 5-HT synthesis were enhanced in the nerve terminal. A decrease in plasma albumin may account for the increase in plasma-free tryptophan levels. An increase in plasma free tryptophan, resulting in an enhanced plasma concentration ratio of free tryptophan/BCAA, may lead to a higher 5-HT concentration in some parts of the brain and, consequently, to central fatigue. It is suggested that provision of BCAA as a dietary supplement may counteract the increase in plasma free tryptophan and thus improve the status of some patients after major surgery.
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PMID:Changes in the albumin binding of tryptophan during postoperative recovery: a possible link with central fatigue? 920 93

This study investigated the effects of pre-exercise branched-chain amino acid (BCAA) administration on blood ammonia levels and on time to exhaustion during treadmill exercise in rats. Adult female Wistar rats were trained on a motor driven treadmill. After a 24-h fast, rats were injected intraperitoneally (i.p.) with 1 mL of placebo or BCAA (30 mg), 5 min before performing 30 min of submaximal exercise (N = 18) or running to exhaustion (N = 12). In both cases, rats were sacrificed immediately following exercise, and blood was collected for the measurement of glucose, nonesterified fatty acid (NEFA), lactic acid, BCAA, ammonia, and free-tryptophan (free-TRP) levels. Control values were obtained from sedentary rats that were subjected to identical treatments and procedures (N = 30). Plasma BCAA levels increased threefold within 5 min after BCAA administration. Mean run time to exhaustion was significantly longer (P < 0.01) after BCAA administration (99 +/- 9 min) compared with placebo (76 +/- 4 min). During exercise, blood ammonia levels were significantly higher (P < 0.01) in the BCAA treated compared with those in the placebo treated rats both in the 30-min exercise bout (113 +/- 25 mumol.L-1 (BCAA) vs 89 +/- 16 mumol.L-1) and following exercise to exhaustion (186 +/- 44 mumol.L-1 (BCAA) vs 123 +/- 19 mumol.L-1). These data demonstrate that BCAA administration in rats results in enhanced endurance performance and an increase in blood ammonia during exercise.
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PMID:Pre-exercise branched-chain amino acid administration increases endurance performance in rats. 930 29

We hypothesized that central fatigue may have a role in limiting the endurance capacity of horses. Therefore, we tested the effect of infusing tryptophan and/or glucose on endurance time and plasma concentrations of free tryptophan and other substrates thought to affect tryptophan uptake into the brain of seven mares (3-4 yr of age, 353-435 kg) that ran on a treadmill at 50% of maximal O2 consumption to fatigue. With use of a counterbalanced crossover design, the horses were infused with tryptophan (100 mg/kg in saline solution) or a similar volume of saline solution (placebo) before exercise. During exercise, horses received infusions of glucose (2 g/min, 50% wt/vol) or a similar volume of saline. Thus the treatments were 1) tryptophan and glucose (T & G), 2) tryptophan and placebo (T & P), 3) placebo and glucose (P & G), and 4) placebo and placebo (P & P). Mean heart rate, hematocrit, and concentration of plasma total solids before and during exercise were similar for all trials. Mean time to exhaustion was reduced (P < 0.05) for T & P and T & G compared with P & P [86.1 +/- 6.9 and 87.1 +/- 6.8 vs. 102.3 +/- 10.3 (SE) min], whereas endurance for P & G (122.4 +/- 11.9 min) was greater than for all other trials (P < 0.05). Compared with nontryptophan trials, during the tryptophan trials plasma prolactin increased (P < 0.05) nearly threefold before exercise and almost twofold early in exercise. Muscle glycogen concentrations were reduced (P < 0.05) below preexercise values in the P & G and P & P trials only. However, glucose infusions (P & G) did not affect (P > 0.05) concentrations of plasma free fatty acids or ratios of branched-chain amino acids to free tryptophan. In conclusion, tryptophan infusion reduced endurance time, which was consistent with the central fatigue hypothesis. The failure of glucose infusion to alleviate the effects of tryptophan and the absence of significant muscle glycogen reduction in the tryptophan trials suggest that the early onset of fatigue in the tryptophan trials is not due to a lack of readily available substrate.
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PMID:Effect of tryptophan and of glucose on exercise capacity of horses. 972 51


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