EC:2.3.3.1 - FACTA Search

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)

This study tested the hypothesis that alterations in the metabolic integrity of grafted muscle contribute to its diminished ability to sustain power. Compared with control muscles, muscles studied 120 days after the grafting procedure had lower specific force and sustained power. The sustained power protocol resulted in a depletion of muscle glycogen in control (83%) and grafted (85%) animals. Grafts had lower pre- and poststimulation glycogen, diminished citrate synthase activity, and greater hexokinase activity. No differences were observed in phosphofructokinase activity, glucose transporter GLUT-4 content, fiber type, beta-adrenergic-receptor (beta-AR) density, or binding affinity. Isoproterenol-stimulated adenylyl cyclase activity was lower in grafted vs. control muscle, suggesting an uncoupling of the beta-AR-effector complex. Thus the diminished ability of the grafted muscle to sustain power may be explained, in part, by a decrease in energy available from glycogen stores and/or a decrease in oxidative capacity.
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PMID:Functional deficits in medial gastrocnemius grafts in rats: relation to muscle metabolism and beta-AR regulation. 921 46

Chronic isoproterenol administration produces a rapid, highly reproducible rodent model of cardiac hypertrophy. Yet, despite widespread use of this model, the effects of isoproterenol on in vivo cardiac function and substrate metabolism are unknown. Isoproterenol (5 mg.kg(-1).day(-1)) was infused for 7 days in male Wistar rats (n = 22). In vivo magnetic resonance imaging (MRI) showed that left ventricular mass increased by 37% and end-diastolic and systolic volumes increased by 33% and 73%, respectively, following isoproterenol infusion. Cardiac function at the base of the left ventricle was normal, but apical ejection fraction decreased from 90% to 31% and apical free wall thickening decreased by 94%, accompanied by increased fibrosis and inflammation. Myocardial palmitate oxidation rates were 25% lower, and citrate synthase and medium chain acyl-coenzyme A dehydrogenase activities were reduced by 25% and 29%, respectively, following isoproterenol infusion. Fatty acid transporter protein levels were 11-52% lower and triglyceride concentrations were 55% lower in isoproterenol-infused rat hearts. Basal glycolysis and glycogen concentration were not changed, yet insulin stimulated glycolysis was decreased by 32%, accompanied by 33% lower insulin stimulated glucose transporter, GLUT4, protein levels in rat hearts following isoproterenol infusion, compared with controls. In conclusion, isoproterenol infusion impaired in vivo cardiac function, induced hypertrophy, and decreased both fatty acid and glucose metabolism, changes similar in direction and magnitude to those found in the rat heart following moderate severity myocardial infarction.
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PMID:Isoproterenol induces in vivo functional and metabolic abnormalities: similar to those found in the infarcted rat heart. 1982 79

Hypothyroidism (Hypo) is a risk factor for cardiovascular diseases, including heart failure. Hypo rapidly induces Ca²⁺ mishandling and contractile dysfunction (CD), as well as atrophy and ventricular myocytes (VM) remodeling. Hypo decreases SERCA-to-phospholamban ratio (SERCA/PLB), and thereby contributes to CD. Nevertheless, detailed spatial and temporal Ca²⁺ cycling characterization in VM is missing, and contribution of other structural and functional changes to the mechanism underlying Ca²⁺ mishandling and CD, as transverse tubules (T-T) remodeling, mitochondrial density (D_mit) and energy availability, is unclear. Therefore, in a rat model of Hypo, we aimed to characterize systolic and diastolic Ca²⁺ signaling, T-T remodeling, D_mit, citrate synthase (CS) activity and high-energy phosphate metabolites (ATP and phosphocreatine). We confirmed a decrease in SERCA/PLB (59%), which slowed SERCA activity (48%), reduced SR Ca²⁺ (19%) and blunted Ca²⁺ transient amplitude (41%). Moreover, assessing the rate of SR Ca²⁺ release (dRel/dt), we found that early and maximum dRel/dt decreased, and this correlated with staggered Ca²⁺ transients. However, dRel/dt persisted during Ca²⁺ transient relaxation due to abundant late Ca²⁺ sparks. Isoproterenol significantly up-regulated systolic Ca²⁺ cycling. T-T were unchanged, hence, cannot explain staggered Ca²⁺ transients and altered dRel/dt. Therefore, we suggest that these might be caused by RyR2 clusters desynchronization, due to diminished Ca²⁺-dependent sensitivity of RyR2, which also caused a decrease in diastolic SR Ca²⁺ leak. Furthermore, D_mit was unchanged and CS activity slightly decreased (14%), however, the ratio phosphocreatine/ATP did not change, therefore, energy deficiency cannot account for Ca²⁺ and contractility dysregulation. We conclude that decreased SR Ca²⁺, due to slower SERCA, disrupts systolic RyR2 synchronization, and this underlies CD.
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PMID:Underlying mechanism of the contractile dysfunction in atrophied ventricular myocytes from a murine model of hypothyroidism. 2974 31