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:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies in marine ectotherms from a latitudinal cline have led to the hypothesis that eurythermal adaptation to low mean annual temperatures is energetically costly. To obtain more information on the trade-offs and with that the constraints of thermal adaptation, mitochondrial functions were studied in subpolar lugworms (Arenicola marina L.) adapted to summer cold at the White Sea and were compared with those in boreal specimens from the North Sea, either acclimatized to summer temperatures or to winter cold. During summer, a comparison of mitochondria from subpolar and boreal worms revealed higher succinate oxidation rates and reduced Arrhenius activation energies (Ea) in state 3 respiration at low temperatures, as well as higher proton leakage rates in subpolar lugworms. These differences reflect a higher aerobic capacity in subpolar worms, which is required to maintain motor activity at low but variable environmental temperatures--however, at the expense of an elevated metabolic rate. The lower activity of citrate synthase (CS) found in subpolar worms may indicate a shift in metabolic control within mitochondria. In contrast, acclimatization of boreal lugworms to winter conditions elicited elevated mitochondrial CS activities in parallel with enhanced mitochondrial respiration rates. With falling acclimation temperatures, the significant Arrhenius break temperature in state 3 respiration (11 degrees C) became insignificant (5 degrees C) or even disappeared (0 degrees C) at lower levels of Arrhenius activation energies in the cold, similar to a phenomenon known from hibernating vertebrates. The efficiency of aerobic energy production in winter mitochondria rose as proton leakage in relation to state 3 decreased with cold acclimation, indicated by higher respiratory control ratio values and increased adenosine diphosphate/oxygen (ADP/O) ratios. These transitions indicate reduced metabolic flexibility, possibly paralleled by a loss in aerobic scope and metabolic depression during winter cold. Accordingly, these patterns contrast those found in summer-active, cold-adapted eurytherms at high latitudes.
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PMID:Mitochondrial function in seasonal acclimatization versus latitudinal adaptation to cold in the lugworm Arenicola marina (L.). 1509 38

A canine gracilis model was used to study muscle energy metabolism and enzyme activities after free vascularized muscle transfer. Fifteen male mongrel dogs underwent orthotopic, free transfer of the left gracilis with microneurovascular anastomosis. After a minimum of 10 months' recovery, muscle biopsy specimens were obtained from the transfers and the contralateral controls and analyzed for relative fiber type areas and maximum activities of phosphorylase, hexokinase, phosphofructokinase, glycerol-3-phosphate dehydrogenase (GPDH), pyruvate kinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, 3-hydroxyacyl coenzyme A dehydrogenase (HAD), and creatine phosphokinase. Biopsy specimens obtained before and after a 10 minute, 20-Hz contraction were analyzed for glucose, glycogen, glycolytic intermediates, phosphocreatine, total creatine, and adenine nucleotides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, inosine monophosphate, and inosine). There was no significant transfer versus control difference in type I relative fiber area (45 +/- 4 percent versus 44 +/- 3 percent). Total creatine was significantly reduced in the transferred muscles relative to control (83.1 +/- 3.0 mmol/kg versus 100.6 +/- 5.1 mmol/kg dry weight). Maximal activities of phosphorylase, pyruvate kinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, HAD, and creatine phosphokinase were diminished in transfers relative to controls, although hexokinase activity was significantly higher in the freely transferred gracilis muscles. During the 20-Hz contraction, muscle transfers produced less force initially, although the force/time integral over the 10-minute stimulation was similar in transfers (277 +/- 25 N/g/second) and controls (272 +/- 24 N/g/second). The contraction was associated with significant glvcogen use and lactate accumulation in both transfers and controls, although this was less pronounced for the transfers. Glycolytic flux appeared muted in the transfers relative to controls. Significant, similar high-energy phosphagen reductions and inosine monophosphate accumulation were noted during the contraction in both groups. Contractile activity is associated with the expected pattern of muscle metabolite changes following free vascularized transfer, indicating the components of cellular energy metabolism are not qualitatively altered after microneurovascular muscle transfer. In contrast, quantitative differences suggest that free vascularized muscle transfer can be associated with a muscle enzyme profile consistent with deconditioning and the presence of denervated muscles fibers in the absence of fiber type profile changes.
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PMID:Metabolic characteristics of experimental free vascularized canine gracilis muscle transfers. 1510 85

The present study investigated whether blood lactate removal after supramaximal exercise and fatigue indexes measured during continuous and intermittent supramaximal exercises are related to the maximal muscle oxidative capacity in humans with different training status. Lactate recovery curves were obtained after a 1-min all-out exercise. A biexponential time function was then used to determine the velocity constant of the slow phase (gamma(2)), which denoted the blood lactate removal ability. Fatigue indexes were calculated during all-out (FI(AO)) and repeated 10-s cycling sprints (FI(Sprint)). Biopsies were taken from the vastus lateralis muscle, and maximal ADP-stimulated mitochondrial respiration (V(max)) was evaluated in an oxygraph cell on saponin-permeabilized muscle fibers with pyruvate + malate and glutamate + malate as substrates. Significant relationships were found between gamma(2) and pyruvate + malate V(max) (r = 0.60, P < 0.05), gamma(2) and glutamate + malate V(max) (r = 0.66, P < 0.01), and gamma(2) and citrate synthase activity (r = 0.76, P < 0.01). In addition, gamma(2), glutamate + malate V(max), and pyruvate + malate V(max) were related to FI(AO) (gamma(2) - FI(AO): r = 0.85; P < 0.01; glutamate + malate V(max) - FI(AO): r = 0.70, P < 0.01; and pyruvate + malate V(max) - FI(AO): r = 0.63, P < 0.01) and FI(Sprint) (gamma(2) - FI(Sprint): r = 0.74, P < 0.01; glutamate + malate V(max) - FI(Sprint): r = 0.64, P < 0.01; and pyruvate + malate V(max) - FI(Sprint): r = 0.46, P < 0.01). In conclusion, these results suggested that the maximal muscle oxidative capacity was related to blood lactate removal ability after a 1-min all-out test. Moreover, maximal muscle oxidative capacity and blood lactate removal ability were associated with the delay in the fatigue observed during continuous and intermittent supramaximal exercises in well-trained subjects.
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PMID:Relationships between maximal muscle oxidative capacity and blood lactate removal after supramaximal exercise and fatigue indexes in humans. 1520 91

Thyroid hormone (TH) is an important regulator of mitochondrial content and activity. As mitochondrial content and properties differ depending on muscle-type, we compared mitochondrial regulation and biogenesis by T3 in slow-twitch oxidative (soleus) and fast-twitch mixed muscle (plantaris). Male Wistar rats were treated for 21 to 27 days with T3 (200 microg/kg/day). Oxidative capacity, regulation of mitochondrial respiration by substrates and phosphate acceptors, and transcription factors were studied. In soleus, T3 treatment increased maximal oxygen consumption (Vmax) and the activities of citrate synthase (CS) and cytochrome oxidase (COX) by 100%, 45%, and 71%, respectively (P < 0.001), whereas in plantaris only Vmax increased, by 39% (P < 0.01). ADP-independent respiration rate was increased in soleus muscle by 216% suggesting mitochondrial uncoupling. Mitochondrial substrate utilization in soleus was also influenced by T3, as were mitochondrial enzymes. Lactate dehydrogenase (LDH) activity was elevated in soleus and plantaris by 63% and 11%, respectively (P < 0.01), and soleus creatine kinase was increased by 48% (P < 0.001). T3 increased the mRNA content of the transcriptional co-activator of mitochondrial genes, PGC-1alpha, and the I and IV COX subunits in soleus. The muscle specific response to thyroid hormones could be explained by a lower content of TH receptors in plantaris than soleus. Moreover, TRalpha mRNA level decreased further after T3 treatment. These results demonstrate that TH has a major effect on mitochondrial content, regulation and coupling in slow oxidative muscle, but to a lesser extent in fast muscle, due to the high expression of TH receptors and PGC-1alpha transcription factor.
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PMID:Differential effects of thyroid hormones on energy metabolism of rat slow- and fast-twitch muscles. 1560 82

The purpose of this study was to investigate the hypothesis that cycling efficiency in vivo is related to mitochondrial efficiency measured in vitro and to investigate the effect of training status on these parameters. Nine endurance trained and nine untrained male subjects (V(O2peak) = 60.4 +/- 1.4 and 37.0 +/- 2.0 ml kg(-1) min(-1), respectively) completed an incremental submaximal efficiency test for determination of cycling efficiency (gross efficiency, work efficiency (WE) and delta efficiency). Muscle biopsies were taken from m. vastus lateralis and analysed for mitochondrial respiration, mitochondrial efficiency (MEff; i.e. P/O ratio), UCP3 protein content and fibre type composition (% MHC I). MEff was determined in isolated mitochondria during maximal (state 3) and submaximal (constant rate of ADP infusion) rates of respiration with pyruvate. The rates of mitochondrial respiration and oxidative phosphorylation per muscle mass were about 40% higher in trained subjects but were not different when expressed per unit citrate synthase (CS) activity (a marker of mitochondrial density). Training status had no influence on WE (trained 28.0 +/- 0.5, untrained 27.7 +/- 0.8%, N.S.). Muscle UCP3 was 52% higher in untrained subjects, when expressed per muscle mass (P < 0.05 versus trained). WE was inversely correlated to UCP3 (r = -0.57, P < 0.05) and positively correlated to percentage MHC I (r = 0.58, P < 0.05). MEff was lower (P < 0.05) at submaximal respiration rates (2.39 +/- 0.01 at 50% V(O2max)) than at state 3 (2.48 +/- 0.01) but was neither influenced by training status nor correlated to cycling efficiency. In conclusion cycling efficiency was not influenced by training status and not correlated to MEff, but was related to type I fibres and inversely related to UCP3. The inverse correlation between WE and UCP3 indicates that extrinsic factors may influence UCP3 activity and thus MEff in vivo.
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PMID:Cycling efficiency in humans is related to low UCP3 content and to type I fibres but not to mitochondrial efficiency. 1646 76

We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3 content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria. Respiration was normalized to citrate synthase activity (mitochondrial content) in isolated mitochondria. Maximal ADP-stimulated respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese subjects (all P < 0.05). There were no differences in respiration with palmitoyl-l-carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between the groups. In the whole group, state 3 respiration with pyruvate plus malate and respiration through ETC were negatively associated with A1C, and the proportion of type 2X fibers correlated with markers of insulin resistance (P < 0.05). In conclusion, we provide evidence for a functional impairment in mitochondrial respiration and increased amount of type 2X fibers in muscle of type 2 diabetic patients. These alterations may contribute to the development of type 2 diabetes in humans with obesity.
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PMID:Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. 1735 Nov 50

Creatine kinase (CK) is a phosphotransfer kinase that catalyzes the reversible transfer of a phosphate moiety between ADP and creatine and that is highly expressed in skeletal muscle. In fast glycolytic skeletal muscle, deletion of the cytosolic M isoform of CK in mice (M-CK-/-) leads to a massive increase in the oxidative capacity and of mitochondrial volume. This study was aimed at investigating the transcriptional pathways leading to mitochondrial biogenesis in response to CK deficiency. Wild type and M-CK-/- mice of eleven months of age were used for this study. Gastrocnemius muscles of M-CK-/- mice exhibited a dramatic increase in citrate synthase (+120%) and cytochrome oxidase (COX, +250%) activity, and in mitochondrial DNA (+60%), showing a clear activation of mitochondrial biogenesis. Similarly, mRNA expression of the COXI (mitochondria-encoded) and COXIV (nuclear-encoded) subunits were increased by +103 and +94% respectively. This was accompanied by an increase in the expression of the nuclear respiratory factor (NRF2alpha) and the mitochondrial transcription factor (mtTFA). Expression of the co-activator PGC-1alpha, a master gene in mitochondrial biogenesis was not significantly increased while that of PGC-1beta and PRC, two members of the same family, was moderately increased (+45% and +55% respectively). While the expression of the modulatory calcineurin-interacting protein 1 (MCIP1) was dramatically decreased (-68%) suggesting inactivation of the calcineurin pathway, the metabolic sensor AMPK was activated (+86%) in M-CK-/- mice. These results evidence that mitochondrial biogenesis in response to a metabolic challenge exhibits a unique pattern of regulation, involving activation of the AMPK pathway.
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PMID:Mitochondrial biogenesis in fast skeletal muscle of CK deficient mice. 1805 21

Patients with muscular dystrophy have abnormal cardiac function and decreased high-energy phosphate metabolism. Here, we have determined whether the 8 month old mdx mouse, an animal model of muscular dystrophy, also has abnormal cardiac function and energetics. In vivo cardiac MRI revealed 33% and 104% larger right ventricular end-diastolic and end-systolic volumes, respectively, and 17% lower right ventricular ejection fractions in mdx mice compared with controls. Evidence of left ventricular diastolic dysfunction included 18% lower peak filling rates in mdx mouse hearts. Abnormal cardiac function was accompanied by necrosis and lower citrate synthase activity in the mdx mouse heart, suggesting decreased mitochondrial content. Decreased mitochondrial numbers were associated with 38% lower phosphocreatine concentration, 22% lower total creatine, 36% higher cytosolic free ADP concentration and 1.3 kJ/mol lower free-energy available from ATP hydrolysis in whole isolated, perfused mdx mouse hearts than in controls. Transsarcolemmal creatine uptake was 12% lower in mdx mouse hearts. We conclude that the absence of dystrophin in adult mdx mouse heart, as in the heart of human patient, is associated with right ventricular dilatation, left ventricular diastolic dysfunction and abnormal energy metabolism.
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PMID:Abnormal cardiac morphology, function and energy metabolism in the dystrophic mdx mouse: an MRI and MRS study. 1892 69

Latitudinal comparisons of the Southern Ocean limpet, Nacella concinna, and clam, Laternula elliptica, acclimated to 0.0 degrees C, were used to assess differences in thermal response to two regimes, 0.0, 5.1 to 10.0 degrees C and 2.5, 7.5 to 12.5 degrees C, raised at 5.0 degrees C per week. At each temperature, tissue energy status was measured through a combination of O(2) consumption, intracellular pH, cCO(2), citrate synthase (CS) activity, organic acids (succinate, acetate, propionate), adenylates (ATP, ADP, AMP, ITP, PLA (phospho-L-arginine)) and heart rate. L. elliptica from Signy (60 degrees S) and Rothera (67 degrees S), which experience a similar thermal regime (-2 to +1 degrees C) had the same lethal (7.5-10.0 degrees C), critical (5.1-7.5 degrees C) and pejus (<5.1 degrees C;=getting worse) limits with only small differences in biochemical response. N. concinna, which experiences a wider thermal regime (-2 to +15.8 degrees C), had higher lethal limits (10.0-12.5 degrees C). However, at their Northern geographic limit N. concinna, which live in a warmer environment (South Georgia, 54 degrees S), had a lower critical limit (5.1-10.0 degrees C; O(2), PLA and organic acids) than Rothera and Signy N. concinna (10.0-12.5 degrees C). This lower limit indicates that South Georgia N. concinna have different biochemical responses to temperatures close to their thermal limit, which may make them more vulnerable to future warming trends.
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PMID:Geographical variation in thermal tolerance within Southern Ocean marine ectotherms. 1953 33

In this study, we investigated the hypothesis that the metabolic adaptations observed during steady-state exercise soon after the onset of training would be displayed during the nonsteady period of moderate exercise and would occur in the absence of increases in peak aerobic power (Vo2peak) and in muscle oxidative potential. Nine untrained males [age = 20.8 +/- 0.70 (SE) yr] performed a cycle task at 62% Vo2peak before (Pre-T) and after (Post-T) training for 2 h/day for 5 days at task intensity. Tissue samples extracted from the vastus lateralis at 0 min (before exercise) and at 10, 60, and 180 s of exercise, indicated that at Pre-T, reductions (P < 0.05) in phosphocreatine and increases (P < 0.05) in creatine, inorganic phosphate, calculated free ADP, and free AMP occurred at 60 and 180 s but not at 10 s. At Post-T, the concentrations of all metabolites were blunted (P < 0.05) at 60 s. Training also reduced (P < 0.05) the increase in lactate and the lactate-to-pyruvate ratio observed during exercise at Pre-T. These adaptations occurred in the absence of change in Vo2peak (47.8 +/- 1.7 vs. 49.2 +/- 1.7 mlxkg(-1)xmin(-1)) and in the activities (molxkg protein(-1)xh(-1)) of succinic dehydrogenase (3.48 +/- 0.21 vs. 3.77 +/- 0.35) and citrate synthase (7.48 +/- 0.61 vs. 8.52 +/- 0.65) but not cytochrome oxidase (70.8 +/- 5.1 vs. 79.6 +/- 6.6 U/g protein; P < 0.05). It is concluded that the tighter metabolic control observed following short-term training is initially expressed during the nonsteady state, probably as a result of increases in oxidative phosphorylation that is not dependent on changes in Vo2peak while the role of oxidative potential remains uncertain.
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PMID:Time-dependent effects of short-term training on muscle metabolism during the early phase of exercise. 1971 Mar 84


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