Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acyl dithioesters of CoA have been synthesized by transesterification. The alpha-hydrogens have a spectrally determined pKa of 12.5 +/- 0.14. The hydroxide catalyzed enolization rate is estimated to be 600 M-1.s-1. The absorbance of the dithioester, lambda max = 306 nm, can be used to monitor both the condensation and transesterification reactions that use CoA-Ac as a substrate. For citrate synthase at pH 7.4 Vmax = (4.0 +/- 0.4).10(-4) s-1 and Km = 53 +/- 7.5 microM, which are 2.10(-6) and 3.3-times the Vmax and Km values observed for CoAS-Ac, while for Ac-CoA: choline O-acetyltransferase (EC 2.3.1.6) at pH 7.0 Vmax = (1.1 +/- 0.2).10(-2) mumol.s-1.(mg protein)-1 and Km = 83 +/- 33 microM, which are 0.077 and 10-times the values observed with CoAS-Ac, respectively. The CoA dithioesters are stable at low pH, but hydrolyze with a second-order rate constant of 8.2.10(-2) M-1.s-1 at pH 11.4. The spectral properties of these dithioesters should allow these analogs to be used as probes of the structure of enzyme bound intermediates.
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PMID:Coenzyme A dithioesters: synthesis, characterization and reaction with citrate synthase and acetyl-CoA:choline O-acetyltransferase. 333 28

The developmental patterns of the overall fatty acid elongation and of the last two partial activities of microsomal elongase (dehydration and reduction of 3-hydroxyacyl-CoA) were investigated in the PNS of normal and Trembler mice. Unexpectedly, Trembler microsomes synthesized normal C22-CoA amounts from 3-hydroxyeicosanoyl-CoA (3-OHC20-CoA), a C18-CoA elongation intermediate. Hydroxy- acyl-CoA dehydrase and enoyl-CoA reductase activities were found to be higher in the mutant than in the control, whatever the stage of development. Moreover, C20-CoA elongation led to normal C22-CoA and C24-CoA formation in the mutant whereas C20-CoA formation from C18-CoA was always far lower in Trembler than in control. C18-CoA condensing enzyme emerges as the only elongation step involved in the VLCFA deficit evidenced in Trembler PNS.
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PMID:High metabolism and subsequent elongation of 3-hydroxyeicosanoyl-CoA in very-long-chain fatty acid deficient PNS of Trembler mice. 1050 44

Mitochondria are one of the enzymatic sources of reactive oxygen species (ROS) and could also be a major target for ROS-mediated damage. We hypothesized that ROS may induce mitochondrial DNA (mtDNA) damage, which leads to defects of mtDNA-encoded gene expression and respiratory chain complex enzymes and thus may contribute to the progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). In a murine model of MI and remodeling created by the left anterior descending coronary artery ligation for 4 weeks, the LV was dilated and contractility was diminished. Hydroxyl radicals, which originated from the superoxide anion, and lipid peroxide formation in the mitochondria were both increased in the noninfarcted LV from MI mice. The mtDNA copy number relative to the nuclear gene (18S rRNA) preferentially decreased by 44% in MI by a Southern blot analysis, associated with a parallel decrease (30% to 50% of sham) in the mtDNA-encoded gene transcripts, including the subunits of complex I (ND1, 2, 3, 4, 4L, and 5), complex III (cytochrome b), complex IV (cytochrome c oxidase), and rRNA (12S and 16S). Consistent with these molecular changes, the enzymatic activity of complexes I, III, and IV decreased in MI, whereas, in contrast, complex II and citrate synthase, encoded only by nuclear DNA, both remained at normal levels. An intimate link among ROS, mtDNA damage, and defects in the electron transport function, which may lead to an additional generation of ROS, might play an important role in the development and progression of LV remodeling and failure.
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PMID:Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. 1124 77

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