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)

Metabolic adaptations were studied in papillary muscle from 18 patients undergoing open-heart surgery for mitral valve disease. Analyses were made of myoglobin (MG), the enzymes lactate dehydrogenase (LD) with its isoenzymes, glyceraldehyde phosphate dehydrogenase (GAPDH), phosphofructokinase (PFK), citrate synthase (CS) and creatine kinase (CK) with its isoenzymes MB (CK-MB) and mitochondrial CK (CK-MIT). Myocardial function was assessed with left ventricular angiography. Positive and significant correlations were found between enzymes of oxidative metabolism, i.e. CS on the one hand and MG (r = 0.76), LD1 (r = 0.68), CK-MIT (r = 0.86) and CK-MB (r = 0.65) on the other. Indicators of glycolysis--PFK, GAPDH and LD3--varied independently of CS. LD3% was directly related to GAPDH (r = 0.66). In a sub-group of 12 patients with isolated mitral regurgitation due to myxomatous valve degeneration, LD3% rose (r = 0.72) with increasing myocardial derangement which, however, showed no relationship with any other marker. Thus the capacities of oxidative and glycolytic pathways did not co-vary. Volume load appeared not to affect oxidative capacity, while the anaerobic fraction of glycolysis was increased.
Scand J Thorac Cardiovasc Surg 1989
PMID:Key enzymes of myocardial energy metabolism in papillary muscle of patients with mitral valve disease--relation to left ventricular function. 252 75

The activity of phosphofructokinase (PFK), citrate synthetase (CS), lactate dehydrogenase (LDH), 3-OH-CoA dehydrogenase (ACDH) and cytochrome-c-oxidase (cyt-ox) was measured in right atrial auricle and abdominal rectal muscle biopsies from 24 children, aged 3-12 years, with congenital heart malformations. Twelve children had cyanotic conditions (tetralogy of Fallot or truncus malformations) and 14 were noncyanotic (septal defects or vascular lesions). The cyt-ox activity was significantly higher in the cyanotic subgroup than in the noncyanotic (skeletal muscle: 55.71 +/- 10.4 vs 19.48 +/- 2.6 mmol/g protein/min, p less than 0.01; auricle: 93.1 +/- 11.8 vs 65.58 +/- 7.5, p less than 0.05). There were no significant differences between the activities of PFK, LDH, CS or ACDH in the cyanotic and noncyanotic groups. Within the normal range of hemoglobin and hematocrit, there was no correlation between these parameters and cyt-ox. On the other hand, above the normal range of hemoglobin and hematocrit a correlation coefficient of 0.89 (p less than 0.01) was observed which suggests the higher cyt-ox activity to be an adaptive phenomenon triggered by reduced availability of oxygen.
Thorac Cardiovasc Surg 1988 Dec
PMID:Enzymatic activities in heart and skeletal muscle of children with cyanotic and noncyanotic congenital heart disease. 285 53

Protein synthesis as assessed by the concentration and size distribution of ribosomes was determined together with citrate synthase activity in papillary muscles obtained at open heart surgery from patients with mitral valve disease. The results were compared with corresponding data from the quadriceps femoris muscle of patients undergoing cholecystectomy. Citrate synthase activity was six times higher in papillary muscle than in skeletal muscle. The total ribosome concentration per mg DNA was similar in the two types of muscle. Compared with skeletal muscle, in papillary muscle polyribosomes constituted a higher proportion of the ribosomes (p less than 0.001), and there was a tendency towards larger polyribosome aggregates. It is proposed that the high concentration of polyribosomes in papillary muscle is related to the high oxidative capacity of that tissue.
Cardiovasc Res 1988 Aug
PMID:Protein synthesis assessed by ribosome analysis in human papillary muscle in relation to oxidative capacity: a comparison with skeletal muscle. 324 96

To determine the adaption of myocardial metabolism in mitral regurgitation and mitral stenosis, human papillary muscles obtained during open heart surgery were analysed to measure selective enzyme activities in energy metabolism. All enzyme activities were expressed per unit dry weight muscle, per unit alkali soluble protein, and per unit total creatine and the different results compared. The activities of enzymes concerned with mitochondrial energy production and energy transfer (namely, citrate synthase and mitochondrial creatine kinase) tended to be higher in papillary muscles from hearts with mitral regurgitation than in those with mitral stenosis. The activities of enzymes concerned with cytoplasmic energy production (creatine kinase MM, lactate dehydrogenase, and phosphofructokinase) did not show statistically significant differences between mitral regurgitation and mitral stenosis. The ratio of creatine kinase MB activity to total creatine content showed the greatest difference when papillary muscles from patients with mitral regurgitation and mitral stenosis were compared (31% higher in mitral regurgitation; p less than 0.001). The specific function of creatine kinase MB, which is located in cytoplasm, is not well defined. Creatine kinase MB activity increases with extreme endurance training of human skeletal muscle. Thus the higher creatine kinase MB activity in papillary muscle of mitral regurgitation may represent an adaptation to increased physical demand.
Cardiovasc Res 1987 Mar
PMID:Myocardial enzyme activities in patients with mitral regurgitation or mitral stenosis. 365 86

Myoglobin, muscle fibre diameter, and citrate synthase activity were measured in leg muscle of untrained and trained men and in the myocardium from the apex of the left ventricle and from papillary muscle in patients subjected to open heart surgery. The citrate synthase (CS) activity was 60% higher in trained than in untrained skeletal muscle. In the myocardium it was around four times greater than in untrained skeletal muscle but there was no difference between the apex of the left ventricle and papillary muscle. The fibre diameter varied almost threefold between the different groups of muscles with the largest diameter in untrained skeletal muscle and the with the largest diameter in untrained skeletal muscle and the smallest in papillary muscle. The myoglobin content in trained skeletal muscle did not differ from that of untrained muscle. In the left ventricle it was only 40% of that found in untrained muscle while papillary muscle had almost twice as high a myoglobin content as did the left ventricle. The ratio between myoglobin and fibre diameter, however, was of similar magnitude in skeletal muscle and the left ventricle while it was twice as high in papillary muscle as in the other muscles. In conclusion, the diffusion distance in terms of fibre diameter decreased with increased oxidative capacity (CS activity), when comparing the statistical means of the four different groups. The capacity for oxygen diffusion in relation to oxygen demand measured as the ratio of myoglobin to fibre diameter appeared to be of similar magnitude in skeletal muscle and left ventricle but was higher in papillary muscle.
Cardiovasc Res 1984 Jul
PMID:Myoglobin content in human skeletal muscle and myocardium: relation to fibre size and oxidative capacity. 674 65

Exercise capacity in patients with several types of cardiovascular disease can be improved with dietary carnitine, or carnitine derivatives. Mechanisms underlying this improvement remain largely unknown in part due to a lack of animal models of cardiac pathology in which carnitine derivatives improve exercise tolerance. Our goal was to evaluate the ability of propionyl-L-carnitine (PLC) to improve exercise tolerance in a rat model of exercise intolerance. Fischer 344 rats were followed after either a moderate size MI (n = 22) or sham MI surgery (n = 14). Starting 10 days post-surgery 10 of the MI and 7 of the sham rats received 100 mg/kg/day PLC in drinking water, which increased plasma and LV total l-carnitine concentrations 15-23% (p < 0.05). Rats were followed longitudinally until a statistically significant decrease in exercise capacity occurred in one of the groups, at which time all rats were sacrificed for study of the isolated perfused hearts. At 12-weeks post-MI exercise capacity had decreased 16 +/- 7% (p < 0.05) in the MI group, but remained within 3% of baseline in the MI group that received PLC and the sham groups. Both MI groups exhibited the same degree of LV dilation, decrease in fractional shortening, and blunting of the response to isoproterenol. We conclude that supplemental dietary PLC attenuates the exercise intolerance that occurs secondary to post-MI heart failure in rats, but that this beneficial effect is not attributable to altered LV remodeling, an improved response to beta-adrenergic stimulation, or increased skeletal muscle citrate synthase activity.
Cardiovasc Drugs Ther 2003 Jan
PMID:Exercise intolerance during post-MI heart failure in rats: prevention with supplemental dietary propionyl-L-carnitine. 1284 82

Hypoxia is a consequence of cardiac disease and downregulates mitochondrial metabolism, yet the molecular mechanisms through which this occurs in the heart are incompletely characterized. Therefore, we aimed to use a contracting HL-1 cardiomyocyte model to investigate the effects of hypoxia on mitochondrial metabolism. Cells were exposed to hypoxia (2% O2) for 6, 12, 24, and 48 hours to characterize the metabolic response. Cells were subsequently treated with the hypoxia inducible factor (HIF)-activating compound, dimethyloxalylglycine (DMOG), to determine whether hypoxia-induced mitochondrial changes were HIF dependent or independent, and to assess the suitability of this cultured cardiac cell line for cardiovascular pharmacological studies. Hypoxic cells had increased glycolysis after 24 hours, with glucose transporter 1 and lactate levels increased 5-fold and 15-fold, respectively. After 24 hours of hypoxia, mitochondrial networks were more fragmented but there was no change in citrate synthase activity, indicating that mitochondrial content was unchanged. Cellular oxygen consumption was 30% lower, accompanied by decreases in the enzymatic activities of electron transport chain (ETC) complexes I and IV, and aconitase by 81%, 96%, and 72%, relative to controls. Pharmacological HIF activation with DMOG decreased cellular oxygen consumption by 43%, coincident with decreases in the activities of aconitase and complex I by 26% and 30%, indicating that these adaptations were HIF mediated. In contrast, the hypoxia-mediated decrease in complex IV activity was not replicated by DMOG treatment, suggesting HIF-independent regulation of this complex. In conclusion, 24 hours of hypoxia increased anaerobic glycolysis and decreased mitochondrial respiration, which was associated with changes in ETC and tricarboxylic acid cycle enzyme activities in contracting HL-1 cells. Pharmacological HIF activation in this cardiac cell line allowed both HIF-dependent and independent mitochondrial metabolic changes to be identified.
J Cardiovasc Pharmacol Ther 2014 Nov
PMID:Investigating mitochondrial metabolism in contracting HL-1 cardiomyocytes following hypoxia and pharmacological HIF activation identifies HIF-dependent and independent mechanisms of regulation. 2460 65