Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of sprint training and detraining on supramaximal performances was studied in relation to muscle enzyme adaptations in eight students trained four times a week for 9 weeks on a cycle ergometer. The subjects were tested for peak oxygen uptake (VO2peak), maximal aerobic power (MAP) and maximal short-term power output (Wmax) before and after training and after 7 weeks of detraining. During these periods, biopsies were taken from vastus lateralis muscle for the determination of creatine kinase (CK), adenylate kinase (AK), glycogen phosphorylase (PHOS), hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and its isozymes, 3-hydroxy-acyl-CoA dehydrogenase (HAD) and citrate synthase (CS) activities. Training induced large improvements in Wmax (28%) with slight increases (3%) in VO2peak (P < 0.10). This was associated with a greater glycolytic potential as shown by higher activities for PHOS (9%), PFK (17%) and LDH (31%) after training, without changes in CK and oxidative markers (CS and HAD). Detraining induced significant decreases in VO2peak (4%), MAP (5%) and oxidative markers (10-16%), while Wmax and the anaerobic potential were maintained at a high level. This suggests a high level in supramaximal power output as a result of a muscle glycogenolytic and glycolytic adaptation. A long interruption in training has negligible effects on short-sprint ability and muscle anaerobic potential. On the other hand, a persistent training stimulus is required to maintain high aerobic capacity and muscle oxidative potential. This may contribute to a rapid return to competitive fitness for sprinters and power athletes.
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PMID:Enzyme adaptations of human skeletal muscle during bicycle short-sprint training and detraining. 942 50

Two sisters were investigated at the ages of 20 and 13 years owing to persistently increased serum creatine kinase and recurrent episodes of rhabdomyolysis after emotional stress in the older and myalgias in the younger. The finding of increased levels of cis-5-tetradecenoic acid (C14:1) in plasma, severe hypocarnitinaemia and the absence of a pathological dicarboxylic aciduria in both sisters suggested a very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Reduced [1-(14)C]palmitate oxidation and deficient mitochondrial VLCAD activity in fibroblasts were found. Mutation analysis revealed compound heterozygosity for Asp365His and Arg410His changes. This late-onset, milder clinical presentation differs from the other two more severe infantile phenotypes described, since there is no hypoglycaemia or cardiac disease. Fatty acid oxidation defects should be investigated in all cases with rhabdomyolysis beginning in adolescence or early adulthood.
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PMID:Adolescent myopathic presentation in two sisters with very long-chain acyl-CoA dehydrogenase deficiency. 1051 80

We reported a male infant with multiple acyl CoA dehydrogenase deficiency, probably due to electron transfer flavoprotein dehydrogenase deficiency. He was noted to have severe muscle weakness, a high serum creatine kinase (CK) level up to 6920 IU/L, lipid storage myopathy and fatty liver at 6 months of age. A GC/MS analysis of urinary organic acids showed excess excretion of dicarboxylic acids, including glutaric, 2-hydroxyglutaric, adipic, suberic, sebacic, malonic, ethylmalonic and methylsuccinic acids. On a urinary acylglycine analysis, hexanoylglycine and suberylglycine were increased, but not isovalerylglycine, in amount. No ketosis was noted. The muscle pathology showed increased oil-red O positive lipid droplets of various sizes indicative of lipid storage myopathy. There was diffuse decrease in the activity of cytochrome c oxidase. No ragged-red fibers were noted. His clinical symptoms improved remarkably after the administration of riboflavin (100 mg/day) and L-carnitine (1000 mg/day). He was then diagnosed as having probable riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. The glutaryl CoA dehydrogenase activity in lymphocytes was normal, as were the alpha- and beta-subunits of electron transfer flavoprotein. These findings led us to suspect electron transfer flavoprotein dehydrogenation deficiency. Although he had several episodes of short-term deterioration in clinical and laboratory findings, he developed normally with normal intelligent till 10 years of age.
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PMID:[A case of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II)]. 1072 93

The aim of this study was to evaluate the changes in aerobic and anaerobic metabolism produced by a newly devised short training programme. Five young male volunteers trained daily for 2 weeks on a cycle ergometer. Sessions consisted of 15-s all-out repetitions with 45-s rest periods, plus 30-s all-out repetitions with 12-min rest periods. The number of repetitions was gradually increased up to a maximum of seven. Biopsy samples of the vastus lateralis muscle were taken before and after training. Performance changes were evaluated by two tests, a 30-s all-out test and a maximal progressive test. Significant increases in phosphocreatine (31%) and glycogen (32%) were found at the end of training. In addition, a significant increase was observed in the muscle activity of creatine kinase (44%), phosphofructokinase (106%), lactate dehydrogenase (45%), 3-hydroxy-acyl-CoA dehydrogenase (60%) and citrate synthase (38%). After training, performance of the 30-s all-out test did not increase significantly, while in the maximal progressive test, the maximum oxygen consumption increased from mean (SD) 57.3 (2.6) ml x min(-1) x kg(-1) to 63.8 (3.0) ml min(-1) x kg(-1), and the maximum load from 300 (11) W to 330 (21) W; all changes were significant. In conclusion, this new protocol, which utilises short durations, high loads and long recovery periods, seems to be an effective programme for improving the enzymatic activities of the energetic pathways in a short period of time.
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PMID:A short training programme for the rapid improvement of both aerobic and anaerobic metabolism. 1098 4

In a 14-year-old Japanese girl, manifested recurrent myalgia with elevated serum creatine kinase after moderate exercise became evident, and she was diagnosed as having a myopathic form of very-long chain acyl-CoA dehydrogenase deficiency. Her first clinical symptom of the disease was evident when she was 6 y of age. She had never had hypoglycemic attacks, and hepatomegaly and cardiomyopathy were absent. The diagnosis was suspected on the basis of the urinary organic acid profile after a 36-h fast, long-chain fatty acid-loading test, and the blood acylcarnitine profile. Acyl-CoA dehydrogenase activity with palmitoyl-CoA as a substrate was severely decreased in her fibroblasts, and the amount of very-long chain acyl-CoA dehydrogenase protein was reduced. She was a compound heterozygote of A416T from her father and R450H from her mother. Transient expression of mutant A416T cDNA retained a significant residual acyl-CoA dehydrogenase activity of 10% and 20% normal at 37 degrees C and 30 degrees C, respectively. Specific activity of A416T mutant protein was calculated to be one fifth that of control. In the case of R450H mutant expression, a low residual acyl-CoA dehydrogenase activity of 5% normal was detected at 30 degrees C although significant activity was absent at 37 degrees C. The R450H protein was not detected at 37 degrees C but was clearly detected at one fourth the normal amount at 30 degrees C. These results indicate that both mutations were temperature-sensitive mild mutations, the result being the mildest phenotype of very-long chain acyl-CoA dehydrogenase deficiency.
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PMID:Myopathic form of very-long chain acyl-coa dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl. 1115 18

Short-chain acyl-CoA dehydrogenase deficiency is an inherited metabolic disorder biochemically characterized by tissue accumulation of ethylmalonic (EMA) and methylsuccinic (MSA) acids and clinically by severe neurological symptoms. In the present study we investigated the in vitro effects of EMA and MSA on the activity of creatine kinase (CK) in homogenates from cerebral cortex, skeletal and cardiac muscle of rats. EMA significantly inhibited CK activity from cerebral cortex, but did not affect this activity in skeletal and cardiac muscle. Furthermore, MSA had no effect on this enzyme in all tested tissues. Glutathione (GSH), ascorbic acid and alpha-tocopherol, and the nitric oxide synthase inhibitor L-NAME, did not affect the enzyme activity per se, but GSH fully prevented the inhibitory effect of EMA when co-incubated with EMA. In contrast, alpha-tocopherol, ascorbic acid and L-NAME did not influence the inhibitory effect of the acid. The data suggest that inhibition of brain CK activity by EMA is possibly mediated by oxidation of essential groups of the enzyme, which are protected by the potent intracellular, endogenous, naturally occurring antioxidant GSH.
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PMID:Inhibition of creatine kinase activity in vitro by ethylmalonic acid in cerebral cortex of young rats. 1251 16

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an inherited metabolic disorder biochemically characterized by tissue accumulation of predominantly ethylmalonic acid (EMA) and clinically by neurological dysfunction. In the present study we investigated the in vitro effects of EMA on the activity of the mitochondrial (Mi-CK) and cytosolic (Cy-CK) creatine kinase isoforms from cerebral cortex, skeletal muscle, and cardiac muscle of young rats. CK activities were measured in the mitochondrial and cytosolic fractions prepared from whole-tissue homogenates of 30-day-old Wistar rats. The acid was added to the incubation medium at concentrations ranging from 0.5 to 2.5 mM. EMA had no effect on Cy-CK activity, but significantly inhibited the activity of Mi-CK at 1.0 mM and higher concentrations in the brain. In contrast, both Mi-CK and Cy-CK from skeletal muscle and cardiac muscle were not affected by the metabolite. We also evaluated the effect of the antioxidants glutathione (GSH), ascorbic acid, and alpha-tocopherol and the nitric oxide synthase inhibitor L-NAME on the inhibitory action of EMA on cerebral cortex Mi-CK activity. We observed that the drugs did not modify Mi-CK activity per se, but GSH and ascorbic acid prevented the inhibitory effect of EMA when co-incubated with the acid. In contrast, L-NAME and alpha-tocopherol could not revert the inhibition provoked by EMA on Mi-CK activity. Considering the importance of CK for brain energy homeostasis, it is proposed that the inhibition of Mi-CK activity may be associated to the neurological symptoms characteristic of SCAD deficiency.
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PMID:Ethylmalonic acid inhibits mitochondrial creatine kinase activity from cerebral cortex of young rats in vitro. 1271 29

The objective of the present study was to investigate the in vitro effects of octanoic acid, which accumulates in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and in Reye syndrome, on key enzyme activities of energy metabolism in the cerebral cortex of young rats. The activities of the respiratory chain complexes I-IV, creatine kinase, and Na+,K(+)-ATPase were evaluated. Octanoic acid did not alter the electron transport chain and creatine kinase activities, but, in contrast, significantly inhibited Na+,K(+)-ATPase activity both in synaptic plasma membranes and in homogenates prepared from cerebral cortex. Furthermore, decanoic acid, which is also increased in MCAD deficiency, and oleic acid strongly reduced Na+,K(+)-ATPase activity, whereas palmitic acid had no effect. We also examined the effects of incubating glutathione and trolox (alpha-tocopherol) alone or with octanoic acid on Na+,K(+)-ATPase activity. Tested compounds did not affect Na+,K(+)-ATPase activity by itself, but prevented the inhibitory effect of octanoic acid. These results suggest that inhibition of Na+,K(+)-ATPase activity by octanoic acid is possibly mediated by oxidation of essential groups of the enzyme. Considering that Na+,K(+)-ATPase is critical for normal brain function, it is feasible that the significant inhibition of this enzyme activity by octanoate and also by decanoate may be related to the neurological dysfunction found in patients affected by MCAD deficiency and Reye syndrome.
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PMID:Evidence that antioxidants prevent the inhibition of Na+,K(+)-ATPase activity induced by octanoic acid in rat cerebral cortex in vitro. 1289 42

Patients affected by medium-chain acyl CoA dehydrogenase (MCAD) deficiency, a frequent inborn error of metabolism, suffer from acute episodes of encephalopathy. However, the mechanisms underlying the neuropathology of this disease are poorly known. In the present study, we investigated the in vitro effect of the medium-chain fatty acids (MCFA), at concentrations varying from 0.01 to 3 mM, accumulating in MCAD deficiency on some parameters of energy metabolism in cerebral cortex of young rats. (14)CO(2) production from [U(14)] glucose, [1-(14)C] acetate and [1,5-(14)C] citrate was evaluated by incubating cerebral cortex homogenates from 30-day-old rats in the absence (controls) or presence of octanoic acid, decanoic acid or cis-4-decenoic acid. OA and DA significantly reduced (14)CO(2) production from acetate by around 30-40%, and from glucose by around 70%. DA significantly reduced (14)CO(2) production from citrate by around 40%, while OA did not affect this parameter. cDA inhibited (14)CO(2) production from all tested substrates by around 30-40%. The activities of the respiratory chain complexes and of creatine kinase were also tested in the presence of DA and cDA. Both metabolites significantly inhibited cytochrome c oxidase activity (by 30%) and complex II-III activity (DA, 25%; cDA, 80%). Furthermore, only cDA inhibited complex II activity (by 30%), while complex I-III and citrate synthase were not affected by these MCFA. On the other hand, only cDA reduced the activity of creatine kinase in total homogenates, as well as in mitochondrial and cytosolic fractions from cerebral cortex (by 50%). The data suggest that the major metabolites which accumulate in MCAD deficiency, with particular emphasis to cDA, compromise brain energy metabolism. We presume that these findings may contribute to the understanding of the pathophysiology of the neurological dysfunction of MCAD deficient patients.
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PMID:Inhibition of energy metabolism in cerebral cortex of young rats by the medium-chain fatty acids accumulating in MCAD deficiency. 1556 46

The effect of dietary starch and fat content on serum creatine kinase (CK) activity and substrate availability was evaluated in 4 mares of Quarter Horse-related breeds with polysaccharide storage myopathy (PSSM). Four isocaloric diets ranging in digestible energy (DE) from 21.2% (diet A), 14.8% (B), 8.4% (C), to 3.9% (D) for starch, and 7.2% DE (diet A), 9.9% (B), to 12.7% DE (diet C and D) for fat were fed for 6-week periods (4 weeks with exercise) using a 4 X 4 Latin square design. Postprandial glucose and insulin responses were measured, and 4 hours postexercise, serum CK activity, glucose, insulin, free fatty acids (FFA), and beta-hydroxybutyrate (beta-HBA) were analyzed. Glycogen, glucose-6-phosphate, citrate synthase, 3-hydroxy-acyl-CoA dehydrogenase, lactate dehydrogenase as well as abnormal polysaccharide and lipid content were measured in middle gluteal muscle samples. Postprandial insulin and glucose response was higher for diet A versus D. Log CK activity was higher with diets A, B, and C versus D. Daily insulin was higher and FFA lower on diet A versus B, C, and D, whereas glucose varied only slightly with diet. Muscle oxidative capacity and lipid stores were low in PSSM horses and muscle glycogen and abnormal polysaccharide content high on both diets A and D. Individual variation occurred in the response of PSSM horses to diets differing in starch and fat content. However, for those horses with clinical manifestations of PSSM, a diet with <5% DE starch and >12% DE fat can reduce exertional rhabdomyolysis, potentially by increasing availability of FFA for muscle metabolism.
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PMID:The effect of varying dietary starch and fat content on serum creatine kinase activity and substrate availability in equine polysaccharide storage myopathy. 1563 74


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