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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)

A theoretical metabolic-control-analysis approach has been used to study aspects of glycolytic-flux control and carbon-metabolite regulation, particularly the role of ATP demand (ATPase), in order to determine what general features of the regulation of energy metabolism would be consistent with good carbon-metabolite homeostasis in the face of large changes in carbon flux. On the basis of a semi-quantitative control-analysis model, incorporating estimates of substrate, product and effector actions on the enzymes, the experimentally observed characteristics of glycolytic-flux changes prove to impose constraints on the feasible ranges of these estimates. This leads to the identification of several features of energy metabolism, each of which is necessary but not sufficient to explain the observations; although most of these have been advocated previously (such as AMP activation of phosphofructokinase (PFK), ADP inhibition of ATPase and the role of energy charge or ATP/ADP ratio), our analysis allows their relative importance to be assessed. In the model, the distribution of flux control depends primarily on ADP inhibition of ATPase, and on the activation of PFK by AMP; increase in ADP inhibition of ATPase increases the control on PFK; increase in AMP activation of PFK increases control on ATPase. PFK exerts greater flux control than does ATPase over approximately 50% of the ranges (parameter space) studied, but its control is sufficiently high to achieve sizeable flux increases over less than 20% of the space. Furthermore, control by alteration in PFK activity is shown to result in poor glycolytic metabolite homeostasis over the entire parameter space studied. However, over a large proportion of the parameter space, control by activation of ATPase can lead to large flux changes, i.e. high flux control, coupled with excellent glycolytic-metabolite homeostasis, similar to that observed in working muscle. As well as altering the relative degrees of flux control invested in PFK and ATPase, ADP inhibition of ATPase and AMP activation of PFK have pronounced effects on the homeostatic properties of the system. Stronger ADP inhibition of ATPase results in improved homeostasis of glycolytic metabolites, ATP and ADP in response to PFK activation, whereas stronger activation of PFK by AMP improves the homeostasis of these three quantities in response to ATPase activation. The results are further evidence of the potential for physiological ATP demand to exert control over glycolytic flux, but additionally show that the known effector interactions, in addition to their previously known role in ATP regulation, could contribute to the remarkable homeostasis of glycolytic-metabolite levels observed in vivo. They further indicate that quantitative characterisation of likely domains of behaviour of metabolic systems can be achieved by an algebraic analysis that is not highly dependent on a full and precise knowledge of the molecular details of the kinetic/regulatory properties of the enzymes, but that still allows an assessment of whether hypotheses regarding the system are feasible and sufficient to account for the observations.
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PMID:A control analysis exploration of the role of ATP utilisation in glycolytic-flux control and glycolytic-metabolite-concentration regulation. 999 Mar 13

Two expressed sequence tags were isolated from a porcine skeletal muscle cDNA library and identified as the putative partial cDNAs of the porcine Na+, K(+)-ATPase subunit alpha 2 (ATP1A2) and muscle phosphofructokinase (PFKM) genes after sequencing and homology search. Results of analysis of a pig-rodent somatic cell hybrid panel by PCR allowed the assignments of ATP1A2 to porcine chromosome (chr) 4 and of PFKM to porcine chr 5. These assignments support previously observed conservation of syntenic relationships between human chr 1 and porcine chr 4 and between human chr 12 and porcine chr 5.
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PMID:Mapping of the Na+, K(+)-ATPase subunit alpha 2 (ATP1A2) and muscle phosphofructokinase (PFKM) genes in pig by somatic cell hybrid analysis. 1005 Feb 86

The purpose of this study was to compare two contrasting training models, namely high-resistance training and prolonged submaximal training on the expression of Na+-K+ ATPase and changes in the potential of pathways involved in energy production in human vastus lateralis. The high-resistance training group (VO2peak = 45.3 +/- 1.9 mL kg(-1) min(-1), mean +/- SE, n = 9) performed three sets of six to eight repetitions maximal, each of squats, leg presses and leg extensions, three times per week for 12 weeks, while the prolonged submaximal training group (VO2peak = 44.4 +/- 6.6 mL kg(-1) min(-1), n = 7) cycled 5-6 times per week for 2 h day(-1) at 68% VO2peak for 11 weeks. In the HRT group, Na+-K+ ATPase (pmol g(-1) wet wt), measured with the 3H-ouabain binding technique, showed no change from 0 (289 +/- 22) to 4 weeks (283 +/- 15), increased (P < 0.05) by 16% at 7 weeks and remained stable until 12 weeks (319 +/- 19). For prolonged submaximal training, a 22% increase (P < 0.05) was observed from 0 (278 +/- 31) until 3 weeks (339 +/- 29) with no further changes observed at either 9 weeks (345 +/- 25) or 11 weeks (359 +/- 34). In contrast to high-resistance training, where a 15% increase (P < 0.05) was observed, only in the maximal activity of phosphorylase, prolonged submaximal training resulted in increases in malate dehydrogenase, beta-hydroxyl-CoA dehydrogenase, hexokinase and phosphofructokinase. In contrast to high-resistance training which failed to result in an increase in VO2peak, prolonged submaximal training increased VO2peak by approximately 15%. Only for prolonged exercise training was a relationship observed for VO2peak and Na+-K+-ATPase (r = 0.59; P < 0.05). Correlations between VO2peak and mitochondrial enzyme activities were not significant (P > 0.05) for either training programme. It is concluded that although both training programmes stimulate an up-regulation in Na+-K+ ATPase concentration, only the prolonged submaximal training programme enhances the potential for beta-oxidation, oxidative phosphorylation and glucose phosphorylation.
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PMID:Serial effects of high-resistance and prolonged endurance training on Na+-K+ pump concentration and enzymatic activities in human vastus lateralis. 1009 Mar 29

The critical minimum values of Na,K-ATPase and glycolytic enzyme activities at which the erythrocyte viability is lost were calculated using the mathematical model of the erythrocyte, which included all reactions of glycolysis, adenylate metabolism, ionic balance, and osmotic regulation of erythrocyte volume. The criterion for cell death was an increase in its volume to the level at which it is sequestrated from the circulation or is lysed. In hemolytic anemia associated with hexokinase or pyruvate kinase deficiency, activities of these enzymes measured in patient erythrocytes appeared to be close to the calculated critical values. By contrast, in hemolytic anemia associated with phosphofructokinase, glucosephosphate isomerase, triosephosphate isomerase, or phosphoglycerate kinase deficiency, activities of these enzymes measured in patient erythrocytes were significantly greater than the calculated critical values. In this case, if the deficient enzyme were stable, i.e. its activity in the cell were low, but constant in time, the deficiency observed would not account for the erythrocyte destruction observed and the development of hemolytic anemia. It was shown, however, that in phosphofructokinase, glucosephosphate isomerase, triosephosphate isomerase, or phosphoglycerate kinase deficiency, hemolytic anemia can arise because of the instability of these enzymes in time.
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PMID:Deficiencies of glycolytic enzymes as a possible cause of hemolytic anemia. 1069 93

The metabolic effects of epinephrine on Rana balacanica erythrocyte suspension were studied under normoxia and hypoxia. After epinephrine treatment, a 1.2-fold increase of lactate formation and a 20 per cent decrease of ATP concentration was found under normoxic conditions. These effects were rapid and specific to beta, alpha(1) and alpha(2) antagonists. Glycolysis was stimulated to almost the same extent by both epinephrine and forskolin as normoxic conditions. The stimulation of glycolysis was probably due to stimulation of phosphofructokinase (PFK) as well as to activation of Na(+), K(+)-ATPase. The decrease of ATP was a contributing factor to PFK activation. Despite the high levels of c-AMP at hypoxia, glycolysis was not further induced by epinephrine.
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PMID:Metabolic effects induced by epinephrine in Rana balcanica erythrocytes under normoxic and hypoxic conditions. 1096 56

Inorganic phosphate (Pi) enrichment of the Pi-limited green alga Selenastrum minutum in the dark caused a 2.5-fold increase in the rate of O2 consumption. Alkalization of the media during Pi assimilation was consistent with a H+/Pi cotransport mechanism with a stoichiometry of at least 2 H+ cotransported per Pi. Dark O2 consumption remained enhanced beyond the period of Pi assimilation and did not recover until the medium was reacidified. This result, coupled with an immediate decrease in adenylate energy charge following Pi enrichment, suggested that respiration is regulated by the ATP requirements of a plasmalemma H+-ATPase that is activated to maintain intracellular pH and provide proton motive force to power Pi uptake. Concentrations of tricarboxylic acid cycle intermediates decreased following Pi enrichment and respiratory CO2 efflux increased, indicating that the tricarboxylic acid cycle was activated to supply reductant to the mitochondrial electron transport chain. These results are consistent with direct inhibition of electron transport by ADP limitation. Enhanced rates of starch breakdown and increases in glycolytic metabolites indicated that respiratory carbon flow was activated to supply reductant to the electron transport chain and to rapidly assimilate Pi into metabolic intermediates. The mechanism that initiates glycolytic carbon flow could not be clearly identified by product:substrate ratios due to the complex nature of Pi assimilation. High levels of triose-P and low levels of phosphoenolpyruvate were the primary regulators of pyruvate kinase and phosphofructokinase, respectively.
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PMID:Inorganic Phosphate (Pi) Enhancement of Dark Respiration in the Pi-Limited Green Alga Selenastrum minutum (Interactions between H+/Pi Cotransport, the Plasmalemma H+-ATPase, and Dark Respiratory Carbon Flow). 1223 14

The understanding of control of metabolic processes requires quantitative studies of the importance of the different enzymatic steps for the magnitude of metabolic fluxes and metabolite concentrations. An important element in such studies is the modulation of enzyme activities in small steps above and below the wild-type level. We review a genetic approach that is well suited for both Metabolic Optimization and Metabolic Control Analysis and studies on the importance of a number of glycolytic enzymes for metabolic fluxes in Lactococcus lactis. The glycolytic enzymes phosphofructokinase (PEK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PYK) and lactate dehydrogenase (LDH) are shown to have no significant control on the glycolytic flux in exponentially growing cells of L. lactis MG1363. Introduction of an uncoupled ATPase activity results in uncoupling of glycolysis from biomass production. With MG1363 growing in defined medium supplemented with glucose, the ATP demanding processes do not have a significant control on the glycolytic flux; it appears that glycolysis is running at maximal rate. It is likely that the flux control is distributed over many enzymes in L. lactis, but it cannot yet be excluded that one of the remaining glycolytic steps is a rate-limiting step for the glycolytic flux.
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PMID:Experimental determination of control of glycolysis in Lactococcus lactis. 1236 90

The aims of this study were (i) to assess the differences between men and women in maximal activities of selected enzymes of aerobic and anaerobic pathways involved in skeletal muscle energy production, and (ii) to assess the relationships between maximal enzyme activities, body composition, muscle cross-sectional area (CSA) and fibre type composition. Muscle biopsies were obtained from the tibialis anterior (TA) muscle of 15 men and 15 women (age 20-31 years) with comparable physical activity levels. The muscle CSA was determined by magnetic resonance imaging (MRI). Maximal activities of lactate dehydrogenase (LDH), phosphofructokinase (PFK), beta-hydroxyacyl-coenzyme A dehydrogenase (HAD), succinate dehydrogenase (SDH) and citrate synthase (CS), were assayed spectrophotometrically. The proportion, mean area and relative area (proportion x area) of type 1 and type 2 fibres were determined from muscle biopsies prepared for enzyme histochemistry [myofibrillar adenosine triphosphatase (mATPase)]. The men were significantly taller (+6.6%; P < 0.001) and heavier (+19.1%; P < 0.001), had significantly larger muscle CSA (+19.0%; P < 0.001) and significantly larger areas and relative areas of both type 1 and type 2 fibres (+20.5-31.4%; P = 0.007 to P < 0.001). The men had significantly higher maximal enzyme activities than women for LDH (+27.6%; P = 0.007) and PFK (+25.5%; P = 0.003). There were no significant differences between the men and the women in the activities of HAD (+3.6%; ns), CS (+21.1%; P = 0.084) and SDH (+7.6%; ns). There were significant relationships between height and LDH (r = 0.41; P = 0.023), height and PFK (r = 0.41; P = 0.025), weight and LDH (r = 0.45; P = 0.013), and weight and PFK (r = 0.39; P = 0.032). The relationships were significant between the muscle CSA and the activities of LDH (r = 0.61; P < 0.001) and PFK (r = 0.56; P = 0.001), and between the relative area of type 2 fibres and the activities of LDH (r = 0.49; P = 0.006) and PFK (r = 0.42; P = 0.023). There were no significant relationships between HAD, CS and SDH, and height, weight, muscle CSA and fibre type composition, respectively. These data indicate that the higher maximal activities of LDH and PFK in men are related to the height, weight, muscle CSA and the relative area of type 2 fibres, which are all significantly larger in men than women.
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PMID:Enzyme activities in the tibialis anterior muscle of young moderately active men and women: relationship with body composition, muscle cross-sectional area and fibre type composition. 1239 1

In this study, we show that reactive oxygen species production induced by tumour necrosis factor alpha (TNF-alpha) in L929 cells was associated with a decrease in the steady-state mRNA levels of the mitochondrial transcript ATPase 6-8. Simultaneously, the transcript levels of two nuclear-encoded glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphofructokinase, were increased. These changes were associated with decreased protein levels of the ATPase subunit a (encoded by the mitochondrial ATPase 6 gene) and cytochrome c oxidase subunit II, and increased protein levels of phosphofructokinase. Since TNF-alpha had no effect on the amount of mitochondrial DNA, the results suggested that TNF-alpha acted at the transcriptional and/or post-transcriptional level. Reactive oxygen species scavengers, such as butylated hydroxianisole and butylated hydroxytoluene, blocked the production of free radicals, prevented the down-regulation of ATPase 6-8 transcripts, preserved the protein levels of ATPase subunit a and cytochrome c oxidase subunit II, and attenuated the cytotoxic response to TNF-alpha, indicating a direct link between these two phenomena.
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PMID:Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-alpha in L929 cells. 1247 Feb 98

The role of Na(+)-K(+)-ATPase alpha2-gene BglII polymorphism in the changes of skeletal muscle metabolic properties after a 100-day overfeeding protocol conducted with 12 pairs of monozygotic twins is reported. The activities of oxoglutarate dehydrogenase (OGDH) and phosphofructokinase (PFK) were determined from muscle biopsies. A larger increase in the total fat mass (127 vs. 61%) (P < 0.05) and low-density lipoprotein cholesterol (20 vs. 0.7%) (P = 0.05) in 8.0/8.0-kb [3.3-kb negative (-); n = 7 pairs] than in 8.0/3.3 + 3.3/3.3-kb [3.3-kb positive (+); n = 5 pairs] subjects was observed. OGDH activity decreased in 3.3-kb(-) (-15%), whereas PFK (+26%) as well as the PFK-to-OGDH ratio (90%) increased. In contrast, among 3.3-kb(+), OGDH increased (+54%) together with a decrease in PFK (-1%) and PFK-to-OGDH ratio (-5%). These changes were significantly different between genotypes (P from <0.05 to 0.01). In conclusion, fat mass, low-density lipoprotein cholesterol, and skeletal muscle glycolytic-to-oxidative enzyme ratio increased more in the alpha2-gene 3.3-kb(-) subjects with overfeeding, suggesting more unfavorable metabolic changes compared with the 3.3-kb(+) subjects.
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PMID:Na+-K+-ATPase alpha 2-gene and skeletal muscle characteristics in response to long-term overfeeding. 1249 41


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