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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationships between Na/K pump activity and adenosine triphosphate (ATP) production were determined in isolated rat brain synaptosomes. The activity of the enzyme was modulated by altering [K+]e, [Na+]i, and [ATP]i while synaptosomal oxygen uptake and lactate production were measured simultaneously. KCl increased respiration and glycolysis with an apparent Km of about 1 mM which suggests that, at the [K+]e normally present in brain, 3.3-4 mM, the pump is near saturation with this cation. Depolarization with 6-40 mM KCl had negligible effect on ouabain-sensitive O2 uptake indicating that at the voltages involved the activity of the Na/K ATPase is largely independent of membrane potential. Increases in [Na+]i by addition of veratridine markedly enhanced glycoside-inhibitable respiration and lactate production. Calculations of the rates of ATP synthesis necessary to support the operation of the pump showed that greater than 90% of the energy was derived from oxidative phosphorylation. Consistent with this: (a) the ouabain-sensitive Rb/O2 ratio was close to 12 (i.e., Rb/ATP ratio of 2); (b) inhibition of mitochondrial ATP synthesis by Amytal resulted in a decrease in the glycoside-dependent rate of 86Rb uptake. Analyses of the mechanisms responsible for activation of the energy-producing pathways during enhanced Na and K movements indicate that glycolysis is predominantly stimulated by increase in activity of phosphofructokinase mediated via a rise in the concentrations of adenosine monophosphate [AMP] and inorganic phosphate [Pi] and a fall in the concentration of phosphocreatine [PCr]; the main moving force for the elevation in mitochondrial ATP generation is the decline in [ATP]/[ADP] [Pi] (or equivalent) and consequent readjustments in the ratio of the intramitochondrial pyridine nucleotides [( NAD]m/[NADH]m). Direct stimulation of pyruvate dehydrogenase by calcium appears to be of secondary importance. It is concluded that synaptosomal Na/K pump is fueled primarily by oxidative phosphorylation and that a fall in [ATP]/[ADP][Pi] is the chief factor responsible for increased energy production.
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PMID:Relationships between the neuronal sodium/potassium pump and energy metabolism. Effects of K+, Na+, and adenosine triphosphate in isolated brain synaptosomes. 215 72

We studied the metabolism of the conduction system and the working myocardium in diabetic rat hearts by enzyme histochemistry. The experiment was performed three weeks following the administration of streptozotocin (65 mg/kg) to male Wistar rats. The hearts were quickly excised and tissue was frozen immediately by immersion in isopentane at -30 degrees C and cut into 16 microns thick sections in a cryostat. The PAS positive reaction was increased in the conduction system compared to the working myocardium in control rats. In diabetic rat hearts, these reactions in the working myocardium and the conduction system were strongly increased compared to control hearts. Several enzyme activities, such as phosphofructokinase, pyruvate dehydrogenase, glucose-6-phosphate dehydrogenase, Na-K ATPase, were reduced in both the working myocardium and conduction system of diabetic rat hearts. These results suggest that the changes in metabolic condition also exist in the conduction system of the diabetic rat hearts as well as the working myocardium.
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PMID:Histochemical studies on the conduction system of diabetic rat hearts. 216 29

We have investigated the metabolic adaptations that occur in the thyroxine-treated rat heart. Rats were made hyperthyroid by daily intra-peritoneal injections of thyroxine (35 micrograms/100 g body weight) over seven days. 31P-NMR investigations of isolated glucose-perfused isometric hearts showed that thyroxine treatment caused an increase in Pi (from 4.9 mumols.(g dry wt.)-1 in control hearts to 11.7 mumols.(g dry wt.)-1 in hyperthyroid hearts), a decrease in phosphocreatine (from 36.5 mumols.(g dry wt.)-1 to 21.8 mumols.(g dry wt.)-1) with no change in ATP or ADP concentrations under the same conditions of cardiac work. The unidirectional exchange flux Pi----ATP was measured by saturation transfer NMR in hyperthyroid rat hearts. This exchange (which has been shown to contain a significant glycolytic component) increased by 2.2-fold in thyroxine-treated hearts in comparison to control hearts (to 3.6 mumols.(g dry wt.)-1.s-1, from 1.6 mumols.(g dry wt.)-1.s-1). In parallel experiments, NMR analysis of extracts from hyperthyroid rat hearts showed significantly elevated levels of glucose 6-phosphate, and fructose 6-phosphate. Measurements of enzyme activities isolated from hyperthyroid and control tissue showed a 40% increase in phosphofructokinase activity. These data together with the increased concentration of Pi show that both glycolytic and glycogenolytic fluxes are increased in the hyperthyroid rat heart. This metabolic adaptation may be necessary to cope with the increased number and activity of Na+/K(+)-ATPase pumps that occur in response to thyroxine treatment.
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PMID:Hyperthyroidism results in increased glycolytic capacity in the rat heart. A 31P-NMR study. 224 80

Chronic, rapid ventricular pacing produces congestive heart failure in dogs. The objectives of this study were to determine whether or not (i) in vitro myocardial biochemical alterations reported for heart failure by volume or pressure overload also occurred with heart failure due to rate overload, and (ii) these biochemical alterations were related to relevant in vivo cardiac physiologic alterations. We compared 27 dogs that were paced to advanced heart failure with 21 sham-operated dogs. Dogs with heart failure had 55% lower left ventricular ejection fraction (22.5 +/- 7.6 vs. 50.5 +/- 5.1%) and cardiac index (81 +/- 22 vs. 178 +/- 48 mL.min-1.kg-1), 287% higher pulmonary capillary wedge pressure (27.5 +/- 6.8 vs. 7.1 +/- 3.4 mmHg; 1 mmHg = 133.3 Pa), and 64% greater left ventricular diastolic area (18.4 +/- 3.7 vs. 11.2 +/- 1.3 cm2) (all p less than 0.05). Dogs with heart failure also had (i) 69% lower norepinephrine (232 +/- 139 vs. 747 +/- 220 ng/g protein), (ii) 25-50% lower activities of myofibrillar Ca ATPase (0.188 +/- 0.026 vs. 0.253 +/- 0.051 U/mg myofibrils), sarcoplasmic reticulum Ca-transport ATPase (0.155 +/- 0.074 vs. 0.288 +/- 0.043 U/mg membrane), and the glycolytic enzyme phosphofructokinase (33.4 +/- 10.0 and 47.7 +/- 15.8 U/g), (iii) 32% higher activity of the beta-oxidation enzyme hydroxyacyl-CoA dehydrogenase (11.43 +/- 1.48 vs. 8.67 +/- 1.70 U/g), and (iv) 60% higher activity of Krebs cycle oxoglutarate dehydrogenase (2.89 +/- 0.77 vs. 1.81 +/- 0.95 U/g) (all p less than 0.05). No differences between groups were observed for isozyme patterns and ATPase activity of myosin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies. 232 42

Isoproterenol or forskolin induce a 10-15-fold increase in concentration of cyclic AMP in rat reticulocytes as compared with the basal level of 2.3 +/- 0.3 microM. Glycolysis is stimulated by both compounds transiently more than 2-fold with a peak after 7.5 min followed by an exponential decline. The glycolytic rate in the presence of 10 microM isoproterenol or 10 microM forskolin did not return to basal levels within 60 min of incubation, but was depressed by as much as 50% under the influence of 100 microM forskolin. This phenomenon is designated as metabolic desensitization. The stimulation of glycolysis is probably due to activation of phosphofructokinase as well as to stimulation of Na+,K+-ATPase. The diminished glycolytic flux during the period of metabolic desensitization is accompanied by a decline of glucose 6-phosphate and in the presence of high concentrations of forskolin also by a decrease in glucose 1,6-bisphosphate. A lower rate of influx of glucose is postulated.
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PMID:Activation and desensitization of glycolysis by stimulation of adenylate cyclase in rat reticulocytes. 243 74

Heart transplantation involves chronic effects due to denervation, rejection, and treatment of rejection. The chronically denervated dog heart provides a model for the effects of denervation alone. These hearts have been shown to contain intrinsic neurons with VIP and NPY as possible neurotransmitters. Myocardial tissue noradrenaline concentration falls to very low levels after degeneration of postganglionic sympathetic neurons, but dopamine remains in near-normal concentration and is probably synthesized extraneuronally. ANP is present and released normally; however, the natriuretic response to atrial distension is blunted, suggesting that this response is mainly due to a reflex mechanism. Chronically denervated myocardial tissue exhibits increased oxygen consumption in vitro and increased Na-K, ATPase activity but has normal tissue levels of ATP and creatine phosphate. Glucose oxidation is inhibited in vivo, associated with increased levels of fructose-6-phosphate but normal glucose-6-phosphate, suggesting inhibition of phosphofructokinase activity. However, the enzyme protein concentration of phosphofructokinase, as judged by maximal in vitro activity, is normal. Maximal in vitro activities of succinate dehydrogenase, cytochrome oxidase, monoamine oxidase, calcium-dependent ATPase, and glyceraldehyde-3-dehydrogenase are also normal. From these findings, we would predict that patients with transplanted hearts are likely to show myocardial metabolic inefficiency.
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PMID:Cellular abnormalities in chronically denervated myocardium. Implications for the transplanted heart. 253 6

Compensatory hypertrophy of the rat plantaris muscle (PLT) was induced by ipsilateral gastrocnemius muscle ablation. Following 8 weeks (wks) of hypertrophy, hindlimbs were cast immobilized (HI) for 4 weeks after which weight bearing was unrestricted for 8 wks (recovery). Compensatory hypertrophy increased PLT wet weight/body weight ratio (83%), muscle fiber cross-sectional areas (1.5 to 2 fold), and the percent of slow oxidative (%SO) fibers (2 fold) in the experimental compared to the contralateral sham control muscle. PLT protein content and maximal activities of phosphofructokinase (PFK), mitochondrial glycerol phosphate dehydrogenase, and succinate dehydrogenase were unaltered with muscle hypertrophy. HI produced significant decreases in PFK activity (50%) and muscle fiber cross-sectional areas (50%) but did not significantly change the histochemical myofibrillar ATPase profile. Following remobilization, muscle weight/body weight ratio and maximal enzyme activities recovered to that of aged matched controls. Muscle fiber areas returned to pre-immobilization sizes but were approximately 25% smaller than aged matched control hypertrophy muscles. The %SO fibers in the hypertrophied muscle remained higher than controls but did not return to pre-immobilization values. These results indicate that biochemical and histochemical characteristics of hypertrophied rat PLT recover from HI during 8 wks of normal weight bearing similar to that of normal control muscle. However, the recovery time period was insufficient to allow complete compensation of fiber size to that of the age-matched control animals.
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PMID:Effect of hindlimb immobilization and recovery on compensatory hypertrophied rat plantaris muscle. 253 7

Cell-free extracts of two strictly anaerobic mollicutes, Anaeroplasma intermedium 5LA and Asteroleplasma anaerobium 161T, were tested for enzymic activities of intracellular carbohydrate metabolism. Asteroleplasma anaerobium was also tested for enzymes of purine and pyrimidine metabolism. Both organisms had enzymic activities associated with the nonoxidative portion of the pentose phosphate pathway, and with the Embden-Meyerhoff-Parnas pathway. The 6-phosphofructokinase (PFK) of Asteroleplasma anaerobium was ATP-dependent, whereas the PFK of Anaeroplasma intermedium was PPi-dependent. The two anaerobic mollicutes also differed with respect to the enzymes that converted phosphoenolpyruvate (PEP) to pyruvate; Anaeroplasma intermedium had pyruvate kinase activity, but Asteroleplasma anaerobium had pyruvate, orthophosphate dikinase activity (PPi-dependent). Both organisms had lactate dehydrogenase activity which was activated by fructose 1,6-bisphosphate (Fru-1,6-P2). Anaeroplasma intermedium had activity for PEP carboxykinase (activated by Fru-1,6-P2), but Asteroleplasma anaerobium did not. PEP carboxytransphosphorylase activity was not detected in either organism. Anaeroplasma intermedium had malate dehydrogenase and isocitrate dehydrogenase activities, but it had no activities for the three other tricarboxylic acid cycle enzymes examined; Asteroleplasma anaerobium had malate dehydrogenase activity only. Asteroleplasma anaerobium had enzymic activities for the interconversion of purine nucleobases, (deoxy)ribonucleosides, and (deoxy)ribomononucleotides, including PPi-dependent nucleoside kinase, reported heretofore only in some other mollicutes. Asteroleplasma anaerobium could synthesize dTDP by the thymine salvage pathway if deoxyribose 1-phosphate was provided, and it had dUTPase, ATPase, and dCMP kinase activities. It lacked (deoxy)cytidine deaminase, dCMP deaminase, and deoxycytidine kinase activities.
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PMID:Enzymic activities of carbohydrate, purine, and pyrimidine metabolism in the Anaeroplasmataceae (class Mollicutes). 281 26

The muscle enzymatic changes subsequent to 6 months of strength training followed by 3 months of detraining were examined in 21 physically active men. They were assigned either to a heavy-resistance (HR) or an explosive strength (EX) training program. Muscle biopsies were obtained from m. vastus lateralis for the assessment of activities of the enzymes hexokinase (HK), myofibrillar ATPase (ATPase), citrate synthase (CS), phosphofructokinase (PFK), lactate dehydrogenase (LDH), myokinase (MK) and creatine kinase (CK). The activities were measured on freeze-dried tissue samples using fluorometrical assays. Both groups displayed increased (P less than 0.01-0.001) fast-twitch (FT) fiber area consequent to training with no concomitant hypertrophy of slow-twitch (ST) fiber area. Mean fiber area increased by 16% (P less than 0.001) in HR and 9% (NS) in EX. Following detraining, mean fiber area returned to pretraining value only in EX. HK decreased in both groups (P less than 0.01-0.001) and CK decreased in HR (P less than 0.05). When the two groups were treated together, all enzymes, except for LDH, decreased their activity (P less than 0.05-0.001). It is concluded that 6 months of strength training performed either as heavy-resistance or explosive training is not associated with any increased activities of enzymes reflecting phosphagen, glycolytic, or oxidative metabolism. Instead, the present results suggest that exercise-induced hypertrophy is accompanied by attenuation of certain enzyme activities of importance for ATP regeneration.
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PMID:Enzymatic adaptations consequent to long-term strength training. 295 91

Selected biochemical characteristics of diaphragm muscle were compared among several orders of adult mammals (cattle, swine, rabbit, guinea pig, rat, and mouse) with known differences in resting breathing frequencies (f, range = 15-138). Diaphragms from smaller animals had significantly higher citrate synthase (CS) and phosphofructokinase (PFK) activities and substrate oxidation rates than larger animals. Ranges of activities for CS and PFK were 93-27 and 58-39 mumol.g-1.min-1, respectively; and 34-5 and 19-2 nmol.g-1.min-1 for [U-14C]glucose (GLU) and [1-14C]palmitate (PAL) oxidation, respectively. The percent of native fast myosin (FM) isoforms was significantly different among groups. Mouse diaphragm had the highest % FM (88.6%), whereas the lowest values (7.5%) were observed in cattle diaphragm. Myosin ATPase (M-ATPase, pH 9.8) activity was significantly lower in cattle (0.06 mumol.mg protein-1.min-1) and swine (0.38 mumol.mg protein-1.min-1) diaphragm than in other mammals (range of 1.14-0.67 mumol.mg protein-1.min-1). Correlation coefficients determined among means of measured biochemical parameters and established values of f indicated that CS activity and substrate oxidation rates were significantly correlated with f (r = 0.92, 0.92, 0.86 for CS, GLU, PAL, respectively) and the % FM increased with f. M-ATPase (pH 9.8) was significantly correlated with % FM (r = 0.85), whereas PFK and M-ATPase activities were not closely associated with f. It was concluded that f in mammals is significantly correlated with the biochemical parameters of aerobic capacity and is associated with the percent of FM isoforms in the diaphragm.
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PMID:Biochemical characteristics of mammalian diaphragms. 297 5


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