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)

The adaptation of mitochondrial ATP production rate (MAPR) to training and detraining was evaluated in nine healthy men. Muscle samples (approximately 60 mg) were obtained before and after 6 wk of endurance training and after 3 wk of detraining. MAPR was measured in isolated mitochondria by a bioluminometric method. In addition, the activities of mitochondrial and glycolytic enzymes were determined in skeletal muscle. In response to training, MAPR increased by 70%, with a substrate combination of pyruvate + palmitoyl-L-carnitine + alpha-ketoglutarate + malate, by 50% with only pyruvate + malate, and by 92% with palmitoyl-L-carnitine + malate. With detraining MAPR decreased by 12-28% from the posttraining rate (although not significantly for all substrates). No differences were found when MAPR was related to the protein content in the mitochondrial fraction. The largest increase in mitochondrial enzyme activities induced by training was observed for cytochrome-c oxidase (78%), whereas succinate cytochrome c reductase showed only an 18% increase. The activity of citrate synthase increased by 40% and of glutamate dehydrogenase by 45%. Corresponding changes in maximal O2 uptake were a 9.6% increase by training and a 6.0% reversion after detraining. In conclusion, both MAPR and mitochondrial enzyme activities are shown to increase with endurance training and to decrease with detraining.
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PMID:Adaptation of mitochondrial ATP production in human skeletal muscle to endurance training and detraining. 147 78

Cardiac hypertrophy was produced in embryonic chicks by decreasing the incubation temperature from 38 degrees C to 32 degrees C on day 11. Increases in ventricular protein, RNA, and DNA support the cardiac enlargement. Cytochrome-c oxidase activity and citrate synthase activity were depressed in hypothermic ventricles by 63% and 56%, respectively. No significant differences were seen in enzyme activities in pectoralis muscles. The involvement of mitochondrial gene replication and transcription was evaluated using a cDNA clone for the mitochondrially encoded subunit III of cytochrome-c oxidase (CO III). Quantitative slot-blot analysis demonstrated that the relative CO III mRNA concentration was reduced in hypothermic ventricles. In contrast, the relative mitochondrial DNA concentration was increased in hypothermic ventricles. Taken together, these data indicate that a hypothermia-induced decrease in cytochrome-c oxidase activity is associated with a decrease in CO III mRNA, which is not coupled to a decrease in the mitochondrial DNA copy number. This dissociation of mitochondrial gene replication and transcription may provide a useful model for examining the regulation of mitochondrial biogenesis.
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PMID:Mitochondrial DNA replication and transcription are dissociated during embryonic cardiac hypertrophy. 166 4

We have studied mitochondrial adaptations in muscle subject to chronic denervation, and their relationship to muscle performance, using a model of unilateral sciatic nerve denervation in rats over periods of 2, 5, 8, 14, 21, 28, 35, and 42 days (n = 5-9 rats/day). Time to peak tension (TPT), one-half relaxation time (1/2RT), and endurance performance were evaluated during in situ stimulation of denervated and contralateral gastrocnemius-plantaris muscles. Denervation led to a 70% decline in muscle mass after 42 days. TPT and 1/2RT increased 17 and 30%, respectively, indicating a transformation toward slower muscle. The activities of the enzymes cytochrome-c oxidase (CYTOX), succinate dehydrogenase, and citrate synthase were decreased by 8-14 days, and by 42 days these were 34-58% of control. The mitochondrial phospholipid cardiolipin was reduced earlier, by 5 days, and gradually decreased to 37% of control. Thus phospholipid removal appears to precede the loss of enzyme activity during decreases in mitochondrial content. Endurance performance was reduced in parallel with decreases in enzyme activity and cardiolipin. Cytochrome c mRNA levels decreased to 52% of control by 5 days. Denervation resulted in coordinated changes in mRNA levels encoding the nuclear-derived CYTOX subunit VIc and the mitochondrially derived CYTOX subunit III. However, changes in CYTOX activity did not always parallel alterations in subunit mRNA levels. Thus transcriptional and translational mechanisms operate in regulating mitochondrial gene expression during denervation.
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PMID:Mitochondrial adaptations in denervated muscle: relationship to muscle performance. 185 Jan 97

In vitro translation of maize scutellar polysome-bound RNA and poly(A)+RNA produces a precursor for the mitochondrial superoxide dismutase (SOD-3) of maize, which can be immunoprecipitated with SOD-3 monospecific antibodies. The precursor SOD-3 (preSOD-3) has both a greater molecular weight and a more positive isoelectric point than the mature (purified) SOD-3. These differences were not observed for the cytosolic isozyme (SOD-4) which was similarly synthesized and isolated. PreSOD-3 specifically associates with maize mitochondria when incubated in vitro, whereas SOD-4 does not. The ionophore valinomycin (at concentrations of over 1 microM) inhibits the uptake of preSOD-3 into mitochondria. The integrity of the mitochondrial preparations was determined by assay of oxygen consumption, citrate synthase, and cytochrome-c oxidase activity.
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PMID:In vitro synthesis, importation and processing of Mn-superoxide dismutase (SOD-3) into maize mitochondria. 244 81

1. The activities of phosphofructokinase (PFK), citrate synthetase (CS), lactate dehydrogenase (LDH), 3-hydroxyacyl-CoA dehydrogenase (ACDH) and cytochrome-c oxidase(Cyt-ox) in the calf muscle tissue were compared in subjects with intermittent claudication (n = 38) and controls (n = 20). The activities of CS, ACDH and Cyt-ox were increased and the activity of Cytox was positively correlated to the maximal walking distance (MWD) in the patients. 2. Thirty-three patients with intermittent claudication were randomized to three treatment groups: (1) operative surgery, (2) operative surgery supplemented with physical training and (3) physical training alone. Before and after 6-12 months of treatment, symptom-free walking distance (SFWD), MWD, ankle-brachial blood pressure quotient (ankle index), maximal plethysmographic calf blood flow (MPBF) and the activities of PFK, CS, LDH, ACDH and Cyt-ox were measured. 3. SFWD and MWD increased in all three groups. Ankle index and MPBF increased in groups 1 and 2, but were unchanged in group 3. The activities of Cyt-ox and CS decreased with operation, but the activity of Cyt-ox was further augmented with training in group 3. Overall, the change in ankle index explained 80-90% of the variability in walking performance. In a separate analysis, the increased activity of Cyt-ox in group 3 was positively correlated to, and explained 31% of the variability in, the improvement in SFWD. 4. These findings indicate that both physical activity and a reduced calf blood flow are necessary conditions for the enzymatic adaptation to take place. A causal relationship between metabolic adaptation in the muscle tissue and walking performance is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscle enzyme adaptation in patients with peripheral arterial insufficiency: spontaneous adaptation, effect of different treatments and consequences on walking performance. 255 5

The purpose of this study was to determine whether severe iron deficiency alters the adaptive response of skeletal muscle fibers to a sustained increase in tonic contractile activity. Seven weanling rabbits consumed a low iron diet and underwent phlebotomy twice weekly for 6 mo, resulting in severe anemia (mean Hb 5.5 g/dl). Compared with control animals, tibialis anterior skeletal muscles of iron-deficient animals exhibited reduced concentrations of cytochrome c (4.4 +/- 0.7 vs. 8.6 +/- 0.7 nmol/g tissue; P less than 0.01), and reduced activities of citrate synthase (83 +/- 10 vs. 133 +/- 13 mU/mg protein; P less than 0.01) and cytochrome-c oxidase (2.2 +/- 0.2 vs. 3.6 +/- 0.5 U/mg protein; P less than 0.05). In these muscles mitochondria were swollen and displayed deformed cristae. Less severe biochemical abnormalities were observed in cardiac and soleus skeletal muscles. Ten days of continuous electrical stimulation of the motor nerve supplying anterior compartment muscles of iron-deficient rabbits increased expression of mitochondrial proteins: cytochrome c was increased to 154% of control levels (P less than 0.05), and cytochrome-c oxidase and citrate synthase activities were increased to 199 and 272% of control levels, respectively (P less than 0.005). In addition, electrical pacing increased the fractional volume of mitochondria observed by electron microscopy and reduced the activity of aldolase A by 28% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activity-induced adaptations in skeletal muscles of iron-deficient rabbits. 284 18

Concentrations of high-energy phosphates and activities of key enzymes of energy metabolism were assessed in hearts from species with differing levels of cardiac power output. Positive correlations were found between resting power output and the total adenylate pool and between citrate synthase activity and the total adenylate pool. Maximum in vitro activity levels of enzymes from energy metabolism were compared with calculated resting cardiac power output and maximal cardiac power output (as reflected by total oligomycin-insensitive adenosine-triphosphatase activity). Three indexes of carbohydrate metabolism (hexokinase, pyruvate kinase, and L-lactate dehydrogenase) all plateau at relatively low levels of energy demand. In contrast, enzymes required for aerobic fatty acid metabolism, (carnitine palmitoyltransferase and 3-hydroxyacyl-CoA dehydrogenase) and for tricarboxylic acid and electron transport (citrate synthase and cytochrome-c oxidase) show consistent increases as ATP demand is elevated. It appears that as capacity for power development by vertebrate hearts, increases across taxa, the elevated demand for ATP is met by expansion of fatty acid based aerobic metabolism and not carbohydrate metabolism.
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PMID:Matching of vertebrate cardiac energy demand to energy metabolism. 295 61

Hepatocytes were prepared from 15 degrees C acclimated catfish (Ictalurus punctatus) and maintained in primary culture for 20 days on biomatrix at 7, 15, and 25 degrees C without hormones or serum to determine if cells can directly adapt to temperature. Specific activities of cytochrome-c oxidase, NADH-cytochrome c reductase, citrate synthase, and glucose-6-phosphate dehydrogenase showed acclimatory rate compensation (7 greater than 15 greater than 25 degrees C cultured); 6-phosphogluconate dehydrogenase had activity changes of 15 greater than 7 greater than 25 degrees C cultured; activity of lactate dehydrogenase occurred in the series 7 greater than 15 = 25 degrees C. Protein synthesis of freshly isolated hepatocytes from catfish acclimated to the three temperatures exhibited acclimatory rate compensation. In contrast, protein synthesis of cultured hepatocytes occurred in the series 15 greater than 25 greater than 7 degrees C cultured. Protein degradation was highest at 25 degrees C followed by cells at 15 and 7 degrees C. Cultured hepatocytes showed incomplete temperature acclimation in vitro by way of enzyme activity changes and of protein synthesis. This suggests that some factor(s), such as hormones, is probably necessary to mediate the full temperature-acclimation process.
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PMID:Can cultured teleost hepatocytes show temperature acclimation? 300 35

The purpose of the study was to verify the influence of several weeks of chronic low-frequency electrical stimulation (LFES) on the metabolic profile and functional capacity of human skeletal muscle. Knee extensor muscles (KEM) of eight subjects were electrically stimulated at 8 Hz for 8 h/day and 6 days/wk. Vastus lateralis muscle samples were taken before, after 4 wk, and after 8 wk of LFES, and activities of anaerobic (creatine kinase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase) and aerobic-oxidative (citrate synthase, 3-hydroxyacyl-CoA dehydrogenase, cytochrome-c oxidase) enzyme markers were determined. KEM dynamic performance was also assessed before, after 4 wk, and after 8 wk of LFES. Activity levels of anaerobic enzymes were not altered, whereas the activity levels of citrate synthase (29%),3-hydroxyacyl-CoA dehydrogenase (22%), and cytochrome-c oxidase (25%) were significantly increased after 4 wk of LFES but were not further increased after 4 additional wk of LFES. KEM performance was also improved (P < 0.05) but leveled off after 4 wk of LFES. Although significant changes were observed, the results of the present study suggest that the muscle characteristics investigated in the current study have a limited capacity of adaptation in response to this form of chronic LFES.
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PMID:Human skeletal muscle adaptation in response to chronic low-frequency electrical stimulation. 783 13

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism. 2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio. 3. Fifty-eight percent of patients reported an uncharacterized 'viral infection' before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase). 4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.
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PMID:Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. 877 36


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