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)

Concentric left ventricular hypertrophy was produced in puppies by coarctation banding of the aorta at age 7 weeks. Hemodynamic, morphologic and biochemical studies were carried out 18 months after the operation. Systolic blood pressure proximal to the aortic constriction was 216 +/- 16 mmHg in experimental dogs compared with 115 +/- 5 mmHg in littermate control dogs. Ejection fraction of control and experimental dogs were 59 +/- 4 and 64 +/- 7, respectively. The left ventricular end-diastolic pressure was 6.0 +/- 0.4 in control and 8.4 +/- 1.1 in experimental dogs. There was no sign of overt heart failure in the experimental dogs. Anatomical analysis of different regions of the heart indicated that LV mass in the experimental dogs was increased by about 60%. Ultrastructure of mitochondria in situ, as observed under electron microscope, was normal both in control and hypertrophic hearts. Mitochondria isolated from epicardial and endocardial regions of the stable hypertrophic hearts showed normal rates of respiration, phosphorylation, citrate synthase, and cytochrome c oxidase activities compared to those isolated from hearts of littermate control dogs. It was, therefore, concluded that mitochondrial function is adequately preserved to meet the increased demand for energy in this model of stable cardiac hypertrophy of long duration.
J Mol Cell Cardiol 1983 Apr
PMID:Mitochondrial function in canine experimental cardiac hypertrophy. 630 71

The expression of both mitochondrial and nuclear genes encoding enzymes involved in electron transport and oxidative phosphorylation was examined in bovine cardiac tissue during early growth, development and aging. The steady state level of mRNAs for mitochondrial genes including ATPase 6. COXII and cyt b increased 2.5-4-fold relative to early fetal levels in late fetal and young adult tissues and showed a marked decline (30-50%) in older adult tissues. Similar results were found with the nuclear genes, COXVB and ATP-beta synthase showing coordinate regulation of the two genomes. An increase in mtDNA copy number correlated with the increase in transcript level. Enzyme activity levels for NADH dehydrogenase and cytochrome c oxidase showed a similar trend, albeit of lesser magnitude. These activity levels contrasted with the activity level of an entirely nuclear-encoded mitochondrial enzyme, citrate synthase, which increased not only throughout development but in the older adult tissue. This study indicates that there is a pattern of increasing mitochondrial and nuclear gene expression for OXPHOS enzymes in developing cardiac tissue and decreasing OXPHOS gene expression in the aging heart.
J Mol Cell Cardiol 1994 Aug
PMID:Mitochondrial gene expression during bovine cardiac growth and development. 779 43

The purpose of this study was to investigate whether vitamin D3 deficiency and 1,25-dihydroxyvitamin D3 treatment affect some aspects of heart metabolism in the rat. To this end, five experimental groups were studied: (1) the control group of the vitamin D3 supplemented rats (Group A); (2) rachitic rats (Group B); (3) rachitic rats treated with 1,25-dihydroxyvitamin D3 (Group C); (4) rats fed a vitamin D-deficient diet (Group D); (5) rats fed a vitamin D-deficient diet and treated with 1,25-dihydroxyvitamin D3 (Group E). The five groups were compared by checking in the heart some metabolic parameters, i.e. citrate content, and enzyme activities in cytosol and mitochondria. Citrate content was higher in the heart of treated animals when compared with the control. As regards the enzymatic activities in heart mitochondria, NAD(+)-dependent isocitrate dehydrogenase remarkably decreased in Group B rats and 1,25-dihydroxyvitamin D3 restored quite normal values. NADP(+)-dependent isocitrate dehydrogenase decreased in Group B and Group D animals, and 1,25-dihydroxyvitamin D3 treatment was effective in restoring control values. Cytochrome c oxidase activity did not change, while citrate synthase showed an increase in all the treated rats. As regards the cytosolic enzymes, fructose-6-phosphate kinase increased in the two groups of vitamin D-deplete rats in comparison with the control. Glyceraldehyde-3-phosphate dehydrogenase and 3-phosphoglycerate kinase showed a similar trend: an increase in all the treated animals. In heart homogenate, acylphosphatase and acid phosphatase activities were also determined. Acylphosphatase increased in the treated rats, while acid phosphatase decreased in the rats injected with 1,25-dihydroxyvitamin D3. These results support the hypothesis of a participation of 1,25-dihydroxyvitamin D3 in some aspects of heart metabolism.
J Mol Cell Cardiol 1994 Nov
PMID:Effect of vitamin D deficiency and 1,25-dihydroxyvitamin D3 on rat heart metabolism. 789 66

The effects of chronic embryonic ethanol exposure were evaluated in chick ventricular muscle. Ethanol treatments were administered on embryonic days 11, 13, 15, and 17 and chicks were sacrificed at various time points following treatments. Fluctuations in embryonic blood ethanol levels were examined following treatments. Developmental increases in the activities of mitochondrial enzymes, cytochrome oxidase (CO) and citrate synthase (CS), were observed. Ethanol exposure resulted in a depression in CO activity, but not CS activity. Since, a maximal depression in CO activity was seen with ethanol treatments of 75 mg/100 g, this dosing paradigm was adopted for subsequent experiments. A tissue-specific effect of ethanol was demonstrated as CO activity was unchanged in atrial, liver, pectoralis, and brain tissues. The role of mitochondrial DNA replication and transcription during the developmental up-regulation and ethanol-induced down-regulation of CO activity was evaluated using a cDNA probe for cytochrome oxidase subunit III (COIII). The relative levels of COIII mRNA and mitochondrial DNA (cpm/mg protein) decreased by 3-fold and 4-fold, respectively, across the developmental time course, while CO activity increased by 3.5-fold. Therefore, increases in mitochondrial DNA and mitochondrial mRNA transcripts are unlikely to be responsible for the developmentally-regulated increases in CO activity. Similarly, embryonic ethanol exposure failed to elicit alterations in COIII mRNA levels, indicating that the ethanol-induced depression in CO activity was not transcriptionally regulated. However, ventricular mitochondrial DNA concentrations were elevated in ethanol-treated embryos, indicating that ethanol-exposure either directly or indirectly induces mitochondrial DNA replication.
J Mol Cell Cardiol 1993 Feb
PMID:Ventricular mitochondrial gene expression during development and following embryonic ethanol exposure. 838 53

Mitochondrial respiratory chain enzyme activities were measured in biopsies of left ventricular myocardium from 25 adults in 3 groups: cardiac transplant recipients with atherosclerotic coronary artery disease (CAD), transplant recipients with idiopathic dilated cardiomyopathy (IDC), and patients with compensatory left ventricular hypertrophy due to aortic valve stenosis (AS). Specific activities of complexes I + III and II + III were 21 +/- 12 and 58 +/- 21 nmol/min/mg of noncollagen protein, respectively, in CAD, and 56 +/- 21 and 96 +/- 57 nmol/min/mg, respectively, in IDC (p < 0.004 and < 0.03, respectively). Specimens from patients with AS had enzyme activities that were intermediate between those from patients with CAD and IDC. Myocardium of patients with transvalvular pressure gradients between 50 and 79 mm Hg showed low activities of complexes I + III and II + III (17 +/- 5 and 62 +/- 17 nmol/min/mg of noncollagen protein, respectively), whereas those with higher pressure gradients between 80 and 100 mm Hg had enzyme activities of complexes I + III and II + III equal to those in IDC (37 +/- 11 and 73 +/- 18 nmol/min/mg, respectively). The same results were obtained when enzyme activities were normalized for the activity of the mitochondrial matrix enzyme citrate synthase. The data suggest that a compensatory metabolic adaptation of the mitochondrial respiratory chain enzymes occurs in both AS and IDC. A reduction in enzyme activities that is observed in heart failure due to CAD and that may explain the contractile dysfunction in these patients cannot be confirmed in IDC. In IDC, the enzyme activities are sustained until very late in the disease.
Am J Cardiol 1993 Aug 15
PMID:Myocardial respiratory chain enzyme activities in idiopathic dilated cardiomyopathy, and comparison with those in atherosclerotic coronary artery disease and valvular aortic stenosis. 839 43

During the fetal and suckling periods of mammalian development, the mother serves as the sole nutritional source for the offspring. As such, the quality of the maternal diet effects growth and development of the offspring during these periods. This study sought to determine if a maternal vitamin D deficiency altered the well characterized development of the neonatal heart. Weaned rat pups (21-day-old) were obtained from mothers who had consumed either a vitamin D-supplemented diet (3000 IU of vitamin D/kg) or a low vitamin D diet (< 200 IU of vitamin D/kg) prior to becoming pregnant and throughout pregnancy and suckling. These pups were sacrificed, hearts excised, and the hearts biochemically analysed for metabolic and contractile protein properties. The pups of dams fed the low vitamin D diet were slightly hypocalcemic relative to those on the supplemented diet (2.28 v 2.41 mumol/l, P < 0.05), had significantly lower body weights (43 v 55 g), heart weights (143 v 174 mg), citrate synthase activity (106 v 147 mumol g-1 min-1), and 3-hydroxyacyl CoA dehydrogenase activity (59 v 91 mumol g-1 min-1). Hexokinase activity (1.98 v 2.02 mumol g-1 min-1), and the distribution of cardiac myosin among its three isoforms (> 85% V1), were unaffected by this dietary deficiency, however myofibrillar protein content was approximately 15% lower in the experimental hearts. These data demonstrate that maternal consumption of a low vitamin D diet results in a general but significant slowing of neonatal cardiac development.
J Mol Cell Cardiol 1995 Jun
PMID:Maternal consumption of a low vitamin D diet retards metabolic and contractile development in the neonatal rat heart. 853 Dec 6

Changes in the capacities of ATP-synthesizing reactions were analysed in residual non-infarcted myocardium following myocardial infarction. Rats were subjected to left coronary artery ligation (MI; n = 11) or to sham operation (sham; n = 18). Two months later, hearts were excised, rinsed and buffer-perfused isovolumically. In vitro pressure-volume relationships were recorded. After separation into left and right ventricles (LV, RV) and atria (LA, RA), samples were analysed for citrate synthase, glycolytic enzymes (phosphofructokinase, glyceraldehyde-3-phosphate-dehydrogenase, lactate dehydrogenase (LDH) and its isoforms) and the creatine kinase (CK) system [total CK, CK isoenzymes (CKBB, CKMB, CKMM and CKmito) and total creatine]. In residual intact heart, citrate synthase activity and activities of most glycolytic enzymes were unchanged, but LDH activity and anaerobic LDH isoenzymes increased significantly. Total creatine kinae activity (6.5 +/- 0.2 IU/mg protein in sham LV) was decreased by chronic myocardial infarction in LV (5.4 +/- 0.3, with P < 0.05 sham v MI) but not in RV (6.2 +/- 0.2). Significant CK isoenzyme shifts occurred in both ventricles "adult" CKmito (32.5 +/- 1.4% in sham LV) was reduced in LV (22.1 +/- 2.1% with P < 0.05 sham v MI) and in RV (19.2 +/- 2.9%, with P < 0.05 sham v MI), "fetal" CKBB and CKMB increased. Total creatine content was reduced by up to 35% in both ventricles. In sham hearts atria had lower total and mitochondrial CK activity, lower total creatine content and higher CKMB and CKBB activity compared to ventricles; however, myocardial infarction induced changes directionally comparable to the changes observed in ventricles. Thus, 2 months after myocardial infarction changes of the capacities of ATP synthesizing reactions are comparable for all heart chambers, with the exception of total CK activity decreasing only in left ventricular tissue.
J Mol Cell Cardiol 1996 Jul
PMID:Regional biochemical remodeling in non-infarcted tissue of rat heart post-myocardial infarction. 884 40

Skeletal muscle biopsies (vastus lateralis) were performed in 12 patients (mean age 47 +/- 11 years) before and at 3 and 12 months after cardiac transplantation. Fiber type analysis revealed a predominance of type II fibers before cardiac transplantation (66 +/- 10%); the ratio did not change after transplantation. Fiber cross-sectional area increased by 35% to 39% in all fiber types by 12 months after cardiac transplantation. Fiber cross-sectional area, however, remained below the reported normal values. The number of capillaries surrounding each fiber did not change after cardiac transplantation. Skeletal muscle enzyme activity of phosphofructokinase, citrate synthase, and beta-hydroxyacyl coenzyme A dehydrogenase increased by 26%, 47%, and 63%, respectively, after cardiac transplantation (p < 0.05). Peak oxygen uptake also increased significantly after cardiac transplantation (19.5 +/- 8.1 ml/kg/min at 12 months vs 9.8 +/- 1.4 ml/kg/min before transplant, p < 0.01); however, uptake remained 40% below that of predicted. Thus, significant improvement in skeletal muscle morphology and biochemistry occurs in the first year after cardiac transplantation in association with improved exercise capacity. Recovery, however, may be incomplete, which could explain residual impairment of exercise capacity in these patients.
Am J Cardiol 1997 Mar 01
PMID:Changes in skeletal muscle morphology and biochemistry after cardiac transplantation. 906 22

Despite reported benefits of exercise training in men with chronic congestive heart failure (CHF) and in both men and women with coronary artery disease, the effects of training in women with CHF have not been throughly investigated. Therefore, 16 women (62 +/- 10 years [mean +/- SD]) with stable, moderate, chronic CHF (left ventricular ejection fraction 28 +/- 8%) were studied in a randomized crossover trial with 8 weeks of knee extensor endurance training and 8 weeks of nontraining. The effects of the exercise-based rehabilitation were assessed in skeletal muscle metabolic capacity, exercise tolerance, and quality of life. The compliance rate in training was 98% and no adverse events occurred during the study period. Training increased the activity of citrate synthase (44%, p <0.0001) and lactate dehydrogenase (23%, p <0.002) in the trained muscles, and an improved oxidative capacity in relation to the glycolytic capacity (23%, p <0.002) was found. Peak oxygen uptake (14%, p <0.0005) and peak work rate (43%, p <0.0001) during incremental exercise increased, and blood lactate concentration during standardized submaximal exercise and during the recovery phase decreased (17%, p <0.05). The distance ambulated during 6 minutes (p <0.03), and the overall (p <0.01), physical (p <0.05), and psychosocial (p <0.03) health-related quality of life improved. Because the skeletal muscle endurance training improved peripheral oxidative capacity, exercise tolerance, and the health-related quality of life without any adverse events, this mode of training can be recommended for women with chronic heart failure.
Am J Cardiol 1997 Oct 15
PMID:Skeletal muscle endurance training improves peripheral oxidative capacity, exercise tolerance, and health-related quality of life in women with chronic congestive heart failure secondary to either ischemic cardiomyopathy or idiopathic dilated cardiomyopathy. 935 72

We have investigated the effect of chronic exposure of rats to an hypoxic environment (10% O2; 3 weeks), on the first step of the intracellular energy transfer process in the myocardium, i.e. the transfer at mitochondrial level of high energy bonds from ATP to creatine. In the left ventricles from rats adapted to normobaric hypoxia, we observed, using the permeabilized fiber technique, that the stimulatory effect of creatine on the mitochondrial respiration in presence of a low ADP concentration (0.1 mM) was attenuated when compared to control. Furthermore, the creatine-induced decrease of the apparent K(m) for ADP of the mitochondrial respiration, which is observed in control, was significantly reduced. Both the basal and maximal respiratory rates of the fibers were unchanged by the hypoxic exposure of the rats. A significant decrease of the total creatine kinase activity from 755 to 630 IU/g wet weight (for control and hypoxic rats, respectively) was detected and was accompanied by a 25% decrease in mitochondrial isoform activity (mitoCK) and in the mitoCK/citrate synthase ratio. In the right ventricles, identical alterations in the effect of creatine on apparent K(m) for ADP were observed while we did not detect any changes in CK activity. The decrease in mitoCK activity and the fall in the reactivity of respiration to creatine could be interpreted as a mechanism for downregulating oxygen demand during chronic hypoxia. The consequences of such alterations on energy metabolism of cardiomyocytes under conditions of reduced oxygen supply are discussed.
J Mol Cell Cardiol 1998 Jul
PMID:Chronic exposure of rats to hypoxic environment alters the mechanism of energy transfer in myocardium. 971 Jul 98


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