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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The uremic syndrome is multifactorial, and affects most tissues and organs. Disturbances in protein and amino acid metabolism may play important roles, especially in chronic uremia, either directly or by production of toxic metabolites, with resultant negative nitrogen (N) balance, muscle wasting, reduced protein synthesis, and characteristically abnormal intracellular free amino acid concentrations. There are also grossly abnormal amino acid levels in the plasma of uremic patients, e.g., increases in conjugated amino acids, high levels of several nonessential and low levels of essential amino acids. The ratios of tyrosine/phenylalanine and of valine/glycine are decreased. The low tryptophan levels may contribute to encephalopathy as a result of an imbalance in neurotransmitter synthesis. Citrulline is found in excess; the explanation is unresolved. There are elevated concentrations of the sulfur-containing amino acids: cystine, taurine, cystathionine, and homocysteine. Excess of the latter is implicated in the atherogenesis of renal failure. Disturbed metabolism and interorgan exchange of amino acids in the uremic state explains some of the abnormalities in tissue and plasma concentrations of individual amino acids. Enzymatic defects are involved in the disturbed metabolism of branched chain amino acids (BCAA), with possible antagonism among them, which impairs growth and amino acid utilization. Carbohydrate intolerance, associated with insensitivity of peripheral tissues to insulin and hyperinsulinemia, elicits decreased plasma BCAA. Protein synthesis rates in normal and pathological conditions are more closely related to the intracellular amino acid pool than to plasma amino acid levels. Concentrations of individual amino acids in the plasma pool are poor indicators of their intracellular concentrations. Muscle contains the largest pool of protein and free amino acids in the body. In chronic renal failure patients, the intracellular concentrations of valine, threonine, lysine, and carnosine are low. With low protein diets and in hemodialysis, serine, tyrosine, and taurine often are also low. The low taurine may be related to fatigue and to uremic cardiomyopathies. The commonly used amino acid supplements generally fail to correct the intracellular amino acid deficits. A "New Formula" has been developed to correct these intracellular amino acid abnormalities, and to supplement a low protein diet. It provides more valine than leucine, increased tyrosine and threonine, and less histidine, leucine, isoleucine, lysine, methionine, and phenylalanine than in formulas customarily used for patients with chronic renal failure. It is uncertain whether other ap
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PMID:Amino acid metabolism in uremia. 267 58

To determine the possible role of altered secretion and effects of insulin in fuel homeostasis during heat exposure, the hormonal and metabolic milieu of three groups of rats were studied. The first was placed at 35 degrees C for 12 days (HE), the second was pair-fed (PF) to the first but maintained at 23 degrees C, and the third was allowed to eat ad libitum at 23 degrees C (C). Plasma insulin, glucagon, glucose, and free fatty acids (FFA), and blood lactate, pyruvate, 3-hydroxybutyrate, and individual amino acids were determined. To further characterize glucoregulation, an intraperitoneal glucose tolerance test (1 mg/g body wt) and isotopic glucose turnover (primed infusion of [3-3H]glucose) were performed. In HE rats, weight was constant for the last third of the period, and metabolic state 4 h after food removal was characterized by euglycemia but hypoinsulinemia, elevated blood pyruvate and FFA, and normal 3-hydroxybutyrate compared with C. Lowered levels of branched-chain amino acids and arginine were found. Fourteen hours after food removal glucose turnover was decreased. However, glucose intolerance accompanied by hyperinsulinemia was also found. Many of these changes were also seen in PF, including constant weight, fasting euglycemia, hypoinsulinemia, elevated FFA, and lowered valine and isoleucine. In contrast, pyruvate concentrations were normal, that of 3-hydroxybutyrate was elevated, and the decrement in glucose turnover was smaller than in HE rats. The glucose tolerance was similar to that of HE but accompanied by hypoinsulinemia. The results in HE suggest decreased energy metabolism, insulin secretion altered in a complex manner, and altered insulin action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucoregulatory and metabolic responses to heat exposure in rats. 637 8

Six amino acids are metabolized in resting muscle. They are leucine, isoleucine, valine, asparagine, aspartate, and glutamate. These amino acids provide the amino groups and probably the ammonia required for synthesis of glutamine and alanine, which are released in excessive amounts in the postabsorptive state and during ingestion of a protein-containing meal. Only leucine and part of the isolecine molecule can be oxidized in muscle as they are converted to acetyl-CoA. The other carbon skeletons are used solely for de novo synthesis of TCA-cycle intermediates and glutamine. The carbon atoms of the released alanine originate primarily from glycolysis of blood glucose and from muscle glycogen (about half each in resting conditions). After consumption of a protein-containing meal, BCAA and glutamate are taken up by muscle and their carbon skeletons are used for de novo synthesis of glutamine. About half of the glutamine released from muscle originates from glutamate taken up from the blood, both after overnight starvation, after prolonged starvation, and after consumption of a mixed meal. Glutamine produced by muscle is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and immune system cells, and fulfils several other important functions in human metabolism. The alanine aminotransferase reaction functions to establish and maintain high concentrations of TCA-cycle intermediates in muscle during the first 10 min of exercise. The increase in concentration of TCA-cycle intermediates probably is needed to increase the flux of the TCA-cycle and meet the increased energy demand of exercise. A gradual increase in leucine oxidation subsequently leads to a carbon drain on the TCA-cycle in glycogen-depleted muscles, and may thus reduce the maximal flux in the TCA-cycle and lead to fatigue. Deamination of amino acids and glutamine synthesis present alternative anaplerotic mechanisms in glycogen-depleted muscles, but only allow exercise at 40-50% of Wmax. One-leg exercise leads to the net breakdown of muscle protein. The liberated amino acids are used for synthesis of TCA-cycle intermediates and glutamine. Today, the importance of this process in endurance exercise in the field (running or cycling) in athletes who ingest carbohydrates is not clear. It is proposed that the maximal flux in the TCA-cycle is reduced in glycogen-depleted muscles due to insufficient TCA-cycle anaplerosis, and that this presents a limitation for the maximal rate of fatty acid oxidation. Interactions between the amino acid pool and the TCA-cycle are suggested to play a central role in the energy metabolism of the exercising muscle.
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PMID:Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. 969 93

Muscle proteins turn over slowly and there are minimal diurnal changes in the size of the muscle protein pool in response to feeding and fasting. Nitrogen balance and tracer studies indicate that protein oxidation and net protein breakdown (degradation--synthesis) is not increased during dynamic exercise at intensities of < or = 70% VO2max. An imbalance between muscle protein synthesis and degradation does exist during one leg knee extensor exercise and during two legged cycling in patients with glycogen phosphorylase deficiency. In these latter cases amino acids liberated from the protein pool are used for synthesis of TCA-cycle intermediates and glutamine. Six amino acids are metabolized in resting muscle: leucine, isoleucine, valine, asparagine, aspartate and glutamate. Only leucine and part of the isoleucine molecule can be converted to acetylCoA and oxidized. The carbon skeleton of the other amino acids is used for synthesis of TCA-cycle intermediates and glutamine. The six amino acids provide the amino groups and the ammonia for synthesis of glutamine and alanine, which are released by muscle in excessive amounts. About half of the glutamine release from muscle originates from glutamate taken up from the blood. Glutamine produced by muscle is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and immune system cells and fulfils several other important functions in human metabolism. The alanine aminotransferase reaction functions to establish and maintain high concentrations of TCA-cycle intermediates and a high TCA cycle flux in the first minutes of exercise. A gradual increase in leucine oxidation subsequently leads to a carbon drain on the TCA-cycle in glycogen depleted muscles and may thus reduce the maximal flux in the TCA-cycle and lead to fatigue. Deamination of amino acids and glutamine synthesis present alternative anaplerotic mechanisms in glycogen depleted muscles but only allow exercise at 40-50% of Wmax. It is proposed that the maximal flux in the TCA-cycle is reduced in glycogen depleted muscles due to insufficient TCA-cycle anaplerosis and that this presents a limitation for the maximal rate of fatty acid oxidation. Interactions between the amino acid pool and the TCA-cycle thus seem to play a central role in the energy metabolism of the exercising muscle.
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PMID:Protein and amino acid metabolism in human muscle. 978 36

Adult female Aedes aegypti (L.), the vector of dengue and yellow fever viruses, have an affinity for feeding on human blood and a tendency to forego feeding on sugar. This observation challenges two tenets of mosquito biology: (1) mosquitoes imbibe plant carbohydrates for synthesis of energy reserves and blood for reproduction and (2) egg production is reduced when mosquitoes feed on human blood compared with blood from other species. Sub-optimal amounts of the amino acid isoleucine in human blood (particularly free isoleucine in plasma) are thought to be responsible for lowered egg production when human blood is ingested. We tested the hypothesis that feeding on human blood is associated with a selective advantage for Ae. aegypti and is an underlying reason for this mosquito's intimate and epidemiologically important relationship with human beings. Our five experiments examined the effects of different isoleucine concentrations on accumulated energy reserves, frequency of host contact, survival, and egg production. When mosquitoes imbibed blood meals over a 7- to 10-d period and were not fed sugar, increased isoleucine concentration decreased energy reserves and did not increase egg production. Aedes aegypti took smaller but more frequent blood meals when feeding on a low-isoleucine human host daily compared with a high-isoleucine mouse host. Previous reports that isoleucine enhances egg production were confirmed only when females were fed sugar, an unusual behavior for most domestic Ae. aegypti populations. Females fed human blood and water had greater age-specific survival (l(x)), reproductive output (m(x)), and cumulative net replacement (R0) than cohorts fed human blood plus sugar or isoleucine-rich mouse blood with or without access to sugar. The unique isoleucine concentration of human blood is associated with Ae. aegypti's unusual propensity to feed preferentially and frequently on humans--a behavior that increases this mosquito's fitness, synthesis of energy reserves, and contact with human hosts, making it an especially effective disseminator of human pathogens.
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PMID:Why do female Aedes aegypti (Diptera: Culicidae) feed preferentially and frequently on human blood? 1137 67

Individual amino acid supplementation affects various types of athletic performance. However, little information on combinations of amino acids is currently available. This study evaluated an amino acid mixture containing L-leucine, L-isoleucine, L-valine, L-arginine, and L-glutamine to 3.6 g of total amino acids per dose. Twenty-three rugby players were given 3.6 g, twice, daily of the amino acid mixture for 90 days (June-August 1994) and blood samples were collected for analyses in September 1993, March 1994, September 1994, and September 1995. After 90 days of supplementation, almost all of the athletes reported improvement in vigor and earlier recovery from fatigue. Significant increases (P<0.05) were observed in hemoglobin, RBC count, hematocrit, and serum iron by amino acid supplementation. Significant increases (P<0.05) were also noted in total cholesterol and low-density lipoprotein along with decreased (P<0.05) alkaline phosphatase. All values reverted to original levels when measured after one year of continued training without supplementation.
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PMID:Amino acid supplementation affects hematological and biochemical parameters in elite rugby players. 1167 7

During long-distance exercise, branched-chain amino acid (BCAA) catabolism could lead to an increase in the blood tryptophan/BCAA ratio and an early onset of 'central fatigue'. Based on these considerations, we studied the modifications of blood serum BCAA and tryptophan (Try) levels in 30 endurance horses competing in rides varying in distance from 20 to 72 km. From all horses, blood samples were drawn just before and just after the end of the ride. Samples were analysed for their leucine (Leu), valine (Val), isoleucine (Iso) and Try levels. Data were processed by anova, using sampling moment and ride as factors, and by LSD post hoc test. Significant differences were recorded among the different distance rides for Leu, Val, Iso, Try, Try/BCAA ratio; the same trend was recorded between samples taken at the start and the end of the race for Val and Leu. The main effect observed was an increase of BCAA levels for all rides, except the 72-km ride; for Try, a significant increase was present in all races, except the 50-km ride. The Try/BCAA ratio decreased in 20- and 50-km races and increased in the others. These data confirm that long-distance exercise involves a mobilization of BCAA. The utilization of BCAA seems to be important in prolonged exercise: in the 72-km ride, we observed a decrease in BCAA blood serum levels, while a major role of Try was indicated by its increase, resulting in a rise of the Try/BCAA ratio.
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PMID:Blood serum branched chain amino acids and tryptophan modifications in horses competing in long-distance rides of different length. 1505 43

Several factors have been identified to cause peripheral fatigue during exercise, whereas the mechanisms behind central fatigue are less well known. Changes in the brain 5-hydroxytryptamine (5-HT) level is one factor that has been suggested to cause fatigue. The rate-limiting step in the synthesis of 5-HT is the transport of tryptophan across the blood-brain barrier. This transport is influenced by the fraction of tryptophan available for transport into the brain and the concentration of the other large neutral amino acids, including the BCAAs (leucine, isoleucine, and valine), which are transported via the same carrier system. Studies in human subjects have shown that the plasma ratio of free tryptophan (unbound to albumin)/BCAAs increases and that tryptophan is taken up by the brain during endurance exercise, suggesting that this may increase the synthesis of 5-HT in the brain. Ingestion of BCAAs increases their concentration in plasma. This may reduce the uptake of tryptophan by the brain and also 5-HT synthesis and thereby delay fatigue. Accordingly, when BCAAs were supplied to human subjects during a standardized cycle ergometer exercise their ratings of perceived exertion and mental fatigue were reduced, and, during a competitive 30-km cross-country race, their performance on different cognitive tests was improved after the race. In some situations the intake of BCAAs also improves physical performance. The results also suggest that ingestion of carbohydrates during exercise delays a possible effect of BCAAs on fatigue since the brain's uptake of tryptophan is reduced.
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PMID:A role for branched-chain amino acids in reducing central fatigue. 1642 44

Metabolism of the colonic mucosa of patients with ulcerative colitis (UC; n=31) and Crohn's disease (CD; n=26) and normal mucosa (control, n=26) was investigated using in vitro high-resolution proton magnetic resonance spectroscopy. Of the 31 UC patients, 20 were in the active phase and 11 were in the remission phase of the disease. Out of 26 CD patients, 20 were in the active phase, while 6 were in the remission phase of the disease. Twenty-nine metabolites were assigned unambiguously in the perchloric acid extract of colonic mucosa. In the active phase of UC and CD, significantly lower (P<or=.05) concentration of amino acids (isoleucine, leucine, valine, alanine, glutamate and glutamine), membrane components (choline, glycerophosphorylcholine and myo-inositol), lactate and succinate were observed compared to normal mucosa of controls. Patients in the active phase of UC and CD also showed increased level of alpha-glucose compared to normal mucosa. Altered level of metabolites indicates decreased protein and carbohydrate metabolism, thereby decreased energy status and deterioration of mucosa integrity during chronic inflammation. In the remission phase of UC and CD, the concentration of most of the metabolites was similar to controls except for lower values of lactate, glycerophosphorylcholine and myo-inositol in UC and Lac in CD. Formate was significantly lower in patients with the active phase of UC compared to patients with the active phase of CD, suggesting the potential of in vitro MRS in the differentiation of these two diseases.
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PMID:Metabolism of the colonic mucosa in patients with inflammatory bowel diseases: an in vitro proton magnetic resonance spectroscopy study. 1859 42

The aim of the present study was to investigate the effect of protein diets, rich in branched chain amino acids (BCAA) on perceived exertion, mental and physical performance during an offshore sailing race that lasted 32 h. Twelve sailors were randomly allocated into one of two groups [Control (CON) and BCAA: n = 6/group]. The BCAA group consumed a standard diet of 11.2 MJ day(-1) (58% carbohydrate, 30% fat, 12% Protein) along with a high-protein supplement of 1.7 MJ day(-1) (40% carbohydrate, 35% protein, 25% fat) and 1.7 MJ day(-1) composed of 50% valine, 35% leucine, and 15% isoleucine. CON was given a standard diet of 14.5 MJ day(-1) (58% carbohydrate, 30% fat and 12% protein). During the race, heart rate was monitored. Subjects self-evaluated their feeling of fatigue every 3 h, and 12 samples of saliva from each subject were collected to perform cortisol assays. Before and after the race a vertical jump and a handgrip test were performed, and mental performance was evaluated with a standardized battery of tests. A significant increase in the feeling of fatigue was noted on the second day (D2) of race in both groups; the increase was higher in CON (P < 0.05). For both groups, salivary cortisol concentration followed a nycthemeral rhythm, with an alteration during the race as evidenced by high midnight cortisol levels between D1 and D2, and significantly decreased cortisol levels observed on D2 (P < 0.05). There was no change in physical performance at the end of the race in both groups. As a significant decrease (P < 0.05) in short-term memory performance was observed only in the CON group. These data indicate that an offshore sailing race enhances the feeling of fatigue, and decreases short-term memory performance. These detrimental consequences are reduced by a high-protein diet with BCAA.
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PMID:Effects of branched-chain amino acids supplementation on physiological and psychological performance during an offshore sailing race. 1870 84


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