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 aim of the present study was to relate changes in muscle oxidative capacity and free fatty acid flux in response to oil supplementation to fuel utilisation during subsequent exercise of varying intensities. Following 10 weeks of oil supplementation there was an increased capacity for fat utilisation during low and moderate intensity exercise as indicated by a lower respiratory exchange ratio (RER) (P<0.05). We suggest that this was contributed to by a parallel increase in the oxidative capacity of muscle as indicated by a significant increase in the activity of muscle citrate synthase (CS) (P<0.05) and trend towards an increase in beta-Hydroxy acyl CoA dehydrogenase (beta-HAD), (P>0.05). In addition, low and moderate intensity exercise was associated with an exercise-induced increase in plasma free fatty acids (FFA) and there was an increased facility for uptake of FFA by working muscle from circulating triglycerides, as suggested by an increase in TL activity (P<0.01). The response to oil supplementation varied between individual horses and the magnitude of response, during the low intensity exercise test, in terms of difference in RER was correlated to the increase in CS activity (r2 = 0.95, P<0.05) following oil supplementation. There was no similar significant correlation with respect to FFA, TL or beta-HAD activity (P>0.05). The hypothesis in this study was that the metabolic adaptation to oil supplementation, in terms of exercise response, was related to individual increases in the activities of CS, beta-HAD or TL. However, the relationship between these parameters was unequivocal and requires further investigation, ideally with a larger group of horses.
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PMID:Effect of dietary lipid on response to exercise: relationship to metabolic adaptation. 1240 63

The objective was to determine the effect of combined antituberculosis (anti-TB) drug therapy and an antioxidant, melatonin, on the free radical and organic acid profiles in an experimental rat model. A combined anti-TB drug, Rifater, consisting of 12.0 mg rifampicin, 0.8 mg isoniazid, and 23.0 mg pyrazinamide and 18.56 microg melatonin/kg body weight per day (corresponding to average physiological human intake) were orally administered to Sprague-Dawley rats. Hydroxyl radical production was monitored by quantifying 2,3-dihydroxybenzoic acid produced after intraperitonial sodium salicylate injections. Organic acid extractions and gas chromatography-coupled mass spectrometry analyses were performed on collected urine samples. The results show hydroxyl radicals (P = 0.0019) and organic acids (P-value range: 0.037 to <0.001), characteristic of a multiple acyl-CoA dehydrogenase defect (MADD), were elevated with Rifater treatment and these elevations were significantly lowered with melatonin pretreatment (P-value range: 0.031 to <0.001), probably because of its inherent antioxidant activity. We conclude that hydroxyl radical production and an increased organic acid profile induced by anti-TB medication indicates inhibition of the electron transport chain. We also conclude that free radicals leading to clinical symptoms associated with an MADD metabolic profile induced by anti-TB treatment could be alleviated by melatonin intervention.
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PMID:Melatonin prevents the free radical and MADD metabolic profiles induced by antituberculosis drugs in an animal model. 1568 64

Glu376, the base involved in substrate alphaH+ abstraction at the active center of medium-chain acyl-CoA dehydrogenase (MCAD), has been mutated to Gln and Gly. The mutants are active; however, their rates of dehydrogenation are lowered by approximately 5 orders of magnitude. Binding of the substrate octanoyl-CoA to Glu376Gln-MCAD involves (at least) two steps. The ensuing dehydrogenation reaction that corresponds to reduction of the flavin cofactor also occurs in two phases. These are interpreted to consist of a first, reversible step, followed by a slower, practically irreversible one. For Glu376Gln-MCAD, the log of the rates of dehydrogenation increases linearly with pH (slope = 1) in the pH range of 6-10, suggesting HO- as a reactant. The rates of the same reactions in D2O have the same pD profile and reflect a solvent kinetic isotope effect (SKIE) of approximately 8.5. Glu376Gln+Glu99Gly-MCAD (studied to assess the role of Glu99 also present at the bottom of the active center cavity) has activities and activity profiles similar to those of Glu376Gln-MCAD. This excludes Glu99 as the active center base for Glu376Gln-MCAD catalysis. Proton inventories for the two phases of the dehydrogenation reaction were investigated at 4 and 25 degrees C. The inventories at 25 degrees C reflect a SKIE of approximately 4.5; the profiles are "bowl-shaped", in which a transition-state contribution predominates. The profiles for the 4 degrees C reaction are very unusual. That for the first phase can be analyzed on a two-step model with one step (80% rate-limiting) having a conformational reorganization with an isotope effect of 90-100, from small isotope effects at many protein sites, and the other step (20% rate-limiting) having an inverse isotope effect of ca. 2, characteristic of the reaction of hydroxide ion as a base. For the second phase, only a contribution from many protein sites with a KIE of approximately 4.5 is observed. The results are compatible with a very rigid active site framework that must undergo rearrangements for dehydrogenation to take place, and specifically to allow access of HO-, the reactant that must neutralize the H+ abstracted from the alphaC-H substrate. The large isotope effects are attributed to the changes in state of several H-bonds that occur during the process.
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PMID:Solvent isotope effects in reactions of human medium-chain acyl-CoA dehydrogenase active site mutants. 1728 88