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)

CBL/57 strain db/db mice exhibit type II (noninsulin-dependent) diabetes. The affected mice are markedly hyperinsulinemic, hyperglycemic, and hypercholesterolemic, and their serum K+ levels are decreased. The brains of the diabetic mice are significantly smaller than those of their lean, control littermates, but the protein concentration is normal. The low brain weight is accompanied by a loss of major fatty acid components within the whole brain, nerve endings, and mitochondrial membranes. Cholesterol levels are low in whole brain but are not significantly different from normal in the synaptosomal membranes. The phospholipid concentration is significantly decreased in whole brain homogenates, crude synaptosomal membranes, and crude mitochondrial membranes of the diabetic mice. In addition, the specific activities of membrane-bound synaptosomal acetylcholinesterase, Na+,K(+)-ATPase, and Mg(2+)-ATPase are decreased in crude synaptosomal membranes of the diabetic mice. The specific activities of carnitine palmitoyltransferase I and carnitine acetyltransferase are significantly increased in the crude mitochondrial fraction isolated from the brains of the type II diabetic mice, whereas the specific activity of pyruvate dehydrogenase complex is decreased. The specific activities of two other mitochondrial enzymes--monoamine oxidase B and citrate synthase--and a cytosolic enzyme--lactate dehydrogenase--are unaltered. The ability to synthesize cyclic AMP is markedly decreased in the brains of the diabetic mice. The concentrations of carnitine and of the amino acids, glutamate, aspartate, glutamine, and serine are unaltered, whereas glycine levels are significantly elevated in the brains of the db/db mice. The data suggest that in vivo the brains of the diabetic mice exhibit a decreased capacity for glucose oxidation and increased capacity for fatty acid oxidation. This hypothesis is supported by the finding that cerebral mitochondria isolated from the db/db mice oxidize [1-14C]palmitate to 14CO2 at a rate almost twice that of control mitochondria. The present findings emphasize the potentially serious alteration of brain metabolism in uncontrolled type II diabetes.
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PMID:Lipid metabolism and membrane composition are altered in the brains of type II diabetic mice. 772 1

The postnatal development of the complexes of the electron transport chain in isolated rat brain mitochondria were investigated. Nonsynaptosomal brain mitochondria were isolated from rats aged 1-60 days, and the activities of mitochondrial complexes I, II-III, IV, V and citrate synthase were measured. There was a significant increase in the activity of complex I from postnatal day 1 to day 21, and in the activities of complex II-III, complex IV and citrate synthase from postnatal day 1 to day 60. In contrast, the activity of complex V increased significantly between postnatal day 1 and day 10 where it attained adult levels. These data are consistent with the increasing demand for mitochondrial ATP production as the brain develops and as aerobic glycolysis becomes the major pathway for energy production.
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PMID:Postnatal development of the complexes of the electron transport chain in isolated rat brain mitochondria. 776 12

Idiopathic dilated cardiomyopathy is associated with derangement of myocardial sarcoplasmic Ca-homeostasis and energy production. The molecular mechanism for these changes is unknown. Accordingly, we used genetic and experimentally-induced models of canine dilated cardiomyopathy and tested the hypothesis that these metabolic changes resulted from altered gene expression, as indicated by mRNA content. We studied dilated cardiomyopathy occurring naturally (n = 9) in Doberman pinschers, and in dogs subjected to rapid ventricular pacing (n = 5), in comparison with normal dogs (n = 9). We determined content and integrity of mRNA's using Northern and slot blotting, and measured activities of their translated product for the Ca-release channel and Ca-ATPase of sarcoplasmic reticulum, lactate dehydrogenase of glycolysis, citrate synthase of the tricarboxylic acid cycle, and for myoglobin, ATP-synthetase and the adenine nucleotide transporter, which are integral in oxidative phosphorylation. We found that, whereas both mRNA content and enzyme activity for markers of Ca-cycling, glycolysis, and oxidative phosphorylation were downregulated (20-80%) in dilated cardiomyopathy, they were upregulated (10-15%) for tricarboxylic acid cycling and for ribosomal RNA. RNA from cardiomyopathic tissue was up to 50% more degraded than for normal hearts in association with a 150% increase in ribonuclease activity. Downregulation of the Ca-cycle was asymmetric, with the Ca-channel being 65% more affected than the Ca-ATPase. This work supports the general paradigm that transcriptional and translational responses to pathophysiology are major determinants of the metabolic response seen in cardiac failure.
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PMID:Myocardial mRNA content and stability, and enzyme activities of Ca-cycling and aerobic metabolism in canine dilated cardiomyopathies. 777 66

In the rat kidney, NaK-ATPase activity increased between days 19 and 20 of gestation (+50%) and between 1 and 24 h after birth (+20%), requiring an increased energy supply. In order to determine whether mitochondrial changes were involved, renal mitochondrial development was investigated from day 19 of gestation to 1 day after birth. Slot-blot analyses of mitochondrial-DNA/nuclear-DNA ratio and determination of citrate synthase activity showed a doubling in the mitochondrial pool between days 19 and 20 of gestation. In isolated mitochondria, oxygen consumption remained unchanged between days 19 and 20 of gestation, and then it was enhanced between days 20 and 21 of gestation (+70%) and between 1 and 24 h after birth (+50%). We also focused on one of the respiratory-chain complexes, ATP synthase, and measured its activity and content during the perinatal period. We demonstrated increases in both activity and content of ATP synthase between days 20 and 21 of gestation and between 1 and 24 h after birth, thus suggesting that changes in ATP synthase activity are ascribed to an increase in the mitochondrial density of ATP synthase complexes. Moreover, the mitochondrial ATP/ADP ratio only increased between 1 and 24 h (+90%), indicating a critical step in the renal respiratory-chain maturation at that time. We therefore conclude that the postnatal enhancement of renal mitochondrial oxidative capacity might depend on protein synthesis de novo and on changes in the adenine nucleotide concentrations.
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PMID:Perinatal maturation of rat kidney mitochondria. 783 86

Although chronic cocaine use is cardiotoxic, its use remains problematic in athletics. Hence adaptive changes induced in the heart by superimposing chronic cocaine use on an exercise training are of interest but remain poorly understood. Therefore this study investigated the effects of cocaine treatment combined with exercise training on the metabolic and contractile properties of the heart. Male Sprague-Dawley rats were assigned to one of four groups: normal sedentary (NS, n = 6), cocaine sedentary (CS, n = 6), normal trained (NT, n = 6), and cocaine trained (CT, n = 6). Trained animals were sprint trained 4 times/week. CS and CT animals received cocaine (25 mg/kg, ip) 6 times/week, 15 min before each exercise bout and 2 additional times per week. After 12 weeks, all animals were sacrificed, and the hearts were removed and analyzed for citrate synthase activity, 3-hydroxyacyl-CoA dehydrogenase activity, Ca(2+)-activated myofibrillar ATPase activity, and myosin isoform distribution. None of the groups demonstrated altered cardiac metabolic properties, but cocaine alone and in conjunction with exercise reduced myofibrillar ATPase activity (p < 0.05) and increased expression of the low ATPase myosin isoform, V3. These data suggest that the potential of the citric acid cycle and beta-oxidation is not sensitive to chronic cocaine treatment, but the distribution of cardiac myosin among its three isoforms is affected. Furthermore, high-intensity treadmill training does not interact with cocaine to further alter these properties.
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PMID:Effects of long-term cocaine administration and exercise on cardiac metabolism and isomyosin expression. 801 90

Mechanical properties were measured in single skinned fibers from rat hindlimb muscle to test the hypothesis that the fast type IIb fiber exhibits a higher maximal shortening velocity (Vo) than the fast type IIa fiber and that the difference is directly attributable to a higher myofibrillar adenosinetriphosphatase (ATPase) activity in the type IIb fiber. Additional measurements were made to test the hypotheses that regular endurance exercise increases and decreases the Vo of the type I and IIa fiber, respectively, and that the altered Vo is associated with a corresponding change in the fiber ATPase activity. Rats were exercised by 8-12 wk of treadmill running for 2 h/day, 5 day/wk, up a 15% grade at a speed of 27 m/min. Fiber Vo was determined by the slack test, and the ATPase was measured fluorometrically in the same fiber. The myosin isozyme profile of each fiber was subsequently determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The mean +/- SE Vo (7.9 +/- 0.22 fiber lengths/s) of the type IIb fiber was significantly greater than the type IIa fiber (4.4 +/- 0.21 fiber lengths/s), and the higher Vo was associated with a higher ATPase activity (927 +/- 70 vs. 760 +/- 60 microM.min-1.mm-3). The exercise program induced cardiac hypertrophy and an approximately twofold increase in the mitochondrial marker enzyme citrate synthase. Exercise had no effect on fiber diameter or peak tension per cross-sectional area in any fiber type, but, importantly, it significantly increased (23%) both the Vo and the ATPase activity of the slow type I fiber of the soleus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Shortening velocity and ATPase activity of rat skeletal muscle fibers: effects of endurance exercise training. 802

Recent studies have suggested that modifications in mitochondrial F1-adenosinetriphosphatase (ATPase) activity may play an important role in the regulation of myocardial oxidative phosphorylation. The goal of the present study was to develop and characterize an assay of F1-ATPase activity that could be performed repeatedly on an intact heart under various physiological states. With the use of submitochondrial particles prepared from biopsy samples of canine myocardium, we found reproducible F1-ATPase activity when normalized to the activity of the intramitochondrial enzyme citrate synthase. The oligomycin-sensitive component of the ATPase activity was found to be mainly F1-ATPase. F1-ATPase activity of normal myocardium increased by incubation in high salt-pH buffer, suggesting baseline inhibition. Five minutes after global ischemia, F1-ATPase activity decreased to 60% of baseline. Hypoxia for 10 min resulted in no significant change in F1-ATPase activity. With phenylephrine infusion, myocardial oxygen consumption more than doubled, whereas F1-ATPase activity increased by approximately 30%. Both returned to baseline levels after discontinuation of the drug. With the use of an assay developed to measure F1-ATPase activity of intact myocardium, changes of the enzyme activity were found during both ischemia and at increased work loads. These data suggest that alterations of F1-ATPase activity may contribute to the regulation of myocardial oxidative phosphorylation.
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PMID:Mitochondrial F1-ATPase activity of canine myocardium: effects of hypoxia and stimulation. 802 1

The maximal rates (Vmax) of some enzyme activities related to synaptosomal energy metabolism were studied in different types of synaptosomes from cerebellar cortex of Macaca Fascicularis (Cynomolgus monkey). Different synaptosomal populations, namely "large" and "small" synaptosomes, were isolated from the anterior lobule of the cerebellar cortex of monkeys treated p.o. with dihydroergocriptine at the dose of 12 mg/kg/day before and during the induction of a Parkinson's-like syndrome by MPTP administration (i.v., 0.3 mg/kg/day for 5 days). The enzymes were chosen according to their regulatory role and as markers of the following metabolic pathways: (a) glycolysis ((hexokinase, phosphofructokinase, lactate dehydrogenase), (b) Krebs' (TCA) cycle (citrate synthase, malate dehydrogenase), (c) amino acid, glutamate metabolism (glutamate dehydrogenase, glutamate-pyruvate- and glutamate-oxaloacetate-transaminases), (d) acetylcholine catabolism (acetylcholinesterase) and (e) ATPases, i.e. Na(+)-K(+)-ATPase, Mg(2+)-ATP synthetase, Mg(2+)-ATPase, Ca(2+)-Mg(2+)-ATPase and Ca(2+)-ATPase Low and High affinity for Ca2+. The MPTP administration modified the activities of citrate synthase, malate dehydrogenase, Na(+)-K(+)-ATPase, acetylcholinesterase and glutamate-oxaloacetate transaminase only on selected types of synaptosomes. Pharmacological treatment by dihydroergocriptine was able to recovery at the steady-state levels the activities of these enzymes, thus demonstrating a partial protective effect on these biochemical parameters.
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PMID:Parkinson-like disease by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in Macaca fascicularis: synaptosomal metabolism and action of dihydroergocriptine. 817 63

To investigate the effect of exercise training on calcium movements by isolated cardiac sarcoplasmic reticulum (SR), mongrel dogs either remained sedentary (S) or were exercise-trained (E) via running for a period of 8-10 wk. The trained state was confirmed by the increase in skeletal muscle citrate synthase activity and decreases in submaximal exercise heart rates in the E group but not in the S dogs. The properties of isolated cardiac SR were identical between the groups. The variables tested included ATP-dependent calcium transport and calcium-stimulated ATPase activity. Importantly, there was no difference in spontaneous calcium release which occurred after peak ATP-dependent calcium accumulation was reached. Calcium release from passively loaded vesicles induced by calcium and ionophore also did not differ in the SR isolated from the E dogs. The change in the affinity of the SR Ca ATPase for calcium after the addition of the polyanion, heparin, was similar in both groups, indicating that the regulation of calcium-stimulated ATPase activity by the SR protein, phospholamban, is not modified by exercise training. We conclude that exercise training of 8-10 wk duration does not alter the calcium handling properties of cardiac SR isolated from mongrel dogs.
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PMID:Canine cardiac sarcoplasmic reticulum is not altered with endurance exercise training. 828 11

To investigate the relationship among fibre type, oxidative potential, and Na(+)-K+ ATPase concentration in skeletal muscle, adult male Wistar rats weighing 259 +/- 8 g (mean +/- SE) were sacrificed and the soleus (SOL), extensor digitorum longus (EDL), red vastus lateralis (RV), and white vastus lateralis (WV) removed. These muscles were chosen as being representative of the two major fibre type populations: slow twitch (SOL) and fast twitch (EDL, RV, WV) and exhibiting either a high (SOL, EDL, RV) or low (WV) oxidative potential. Na(+)-K+ ATPase concentration (pmol.g-1 wet weight), measured by the [3H]ouabain binding technique, differed (p < 0.01) only between the WV (238 +/- 7.9) and the SOL (359 +/- 9.6), EDL (365 +/- 10), and RV (403 +/- 12). Similarly, muscle oxidative potential as measured by the maximal activity of citrate synthase was different (p < 0.01) only between the WV and the other three muscles. Citrate synthase activity (mumol.min-1.g-1 wet weight) was 4.0 +/- 0.7, 12.3 +/- 0.9, 9.1 +/- 0.7, and 11.3 +/- 1.0 in the WV, SOL, EDL, and RV, respectively. These results indicate that Na(+)-K+ ATPase concentration is not related to the speed of contraction but to the oxidative potential of the muscle. Since chronic activity is a primary determinant of oxidative potential, it would be expected that increases in Na(+)-K+ ATPase would accompany increases in muscle utilization.
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PMID:Na(+)-K+ ATPase concentration in different adult rat skeletal muscles is related to oxidative potential. 830 1


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