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)

1. Female Wistar rats were randomly assigned to control (C) or exercising (T) groups and subsequently portioned into 1, 3, 5 and 10 day T and C groups. The T groups completed a progressive endurance running program. Biochemical indices of adaptation were measured in cardiac muscle and in plantaris and soleus muscles of C and T animals after their last exercise bout. 2. In cardiac muscle, myofibrillar ATPase activity was significantly elevated in the 3T (0.241 +/- 0.031) and 5T (0.242 +/- 0.013) groups (P less than or equal to 0.05) compared to their respective controls (3C = 0.187 +/- 0.015 and 5C = 0.190 +/- 0.007). 3. After 10 days of training cardiac myofibrillar ATPase activity was elevated by 17% but this was not significant (P greater than or equal to 0.05). 4. No changes in myofibrillar ATPase activity were seen in skeletal muscle (P greater than or equal to 0.05), however, hexokinase activity progressively increased and was significantly elevated in the 3T, 5T and 10T soleus and plantaris muscles of rats over controls (P less than or equal to 0.05). 5. Minimal nonsignificant changes were noted in the hexokinase activity of the hearts of all T groups (P greater than or equal to 0.05). 6. These results indicate that metabolic adaptation of the heart and skeletal muscles takes place after as little as three training sessions. 7. Although the adaptation of the skeletal muscles continually progresses, the adaptation of the heart appears to be transitory.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical adaptation of cardiac and skeletal muscle to physical activity. 182 40

An earlier graph theoretical model of metabolic and gene-expression networks has been modified and extended to include the effect of electrical potentials on binding constants, representation of uncatalyzed processes, and treatment of parallel reactions catalyzed by a single enzyme. Formal operations on the graph, which are facilitated by a set of standardized guidelines, identify the feedback signals in the network and rank them according to their influence. The technique was applied to a model of glycolysis in ascites tumor cells in the absence and presence of 12.5 mM exogenous glucose. Feedback regulation was widely distributed and mostly due to binding of adenine nucleotide cofactors to the enzymes of the network. The major changes in feedback regulation on adding glucose is the relief of inhibition of hexokinase and phosphofructokinase and the activation of pyruvate kinase. We conclude that regulation of tumor cell glycolysis is not restricted to hexokinase or to (Na+,K+)-ATPase as was previously suggested by others.
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PMID:Identification of regulatory properties of metabolic networks by graph theoretical modeling. 189 Aug 46

This study compared the skeletal muscle metabolic adaptations in response to combined eccentric and concentric or concentric resistance training regimens. Twenty-six physically active males were assigned to either the combined eccentric and concentric group (n = 10), the concentric group (n = 10) or the control group (n = 6). The combined eccentric and concentric and the concentric groups performed four to five sets of maximal, voluntary bilateral quadriceps muscle actions at 1.05 rad s-1 using a speed-controlled dynamometer three times per week for 12 weeks. The concentric group performed 12 concentric actions per set, whereas the combined eccentric and concentric group performed six coupled eccentric and concentric actions per set. Bilateral percutaneous muscle biopsies were obtained from m. vastus lateralis at rest pre- and post-training. Tissue samples were analysed for contents of adenosine triphosphate, creatine phosphate and creatine and for enzyme activities of citrate synthase, lactate dehydrogenase, myokinase, phosphofructokinase, hexokinase and Mg2(+)-ATPase using fluorometric techniques. Histochemical staining procedures were employed to determine capillary supply. The overall increase (P less than 0.05) in muscle strength was greater (P less than 0.05) for the combined eccentric and concentric group than for the concentric group. Enzyme or substrate contents and capillary supply were unaltered after either type of training. It is suggested that substantial increases in muscle strength may occur in response to resistance training without enhancing or compromising metabolic function of skeletal muscle.
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PMID:Effects of eccentric and concentric resistance training on skeletal muscle substrates, enzyme activities and capillary supply. 208 17

Administration of vasopressin and glucagon evokes a transient release of Ca2+ from perfused livers. The Ca2+ is released from a pool that is depletable by the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Therefore, the mechanism of the FCCP-stimulated Ca2+ release was examined. The FCCP-stimulated Ca2+ release was associated with a decrease in ATP levels. In the presence of oligomycin, which blocked the FCCP-induced rapid ATP breakdown, FCCP did not release Ca2+ though it still stimulated respiration. The possibility that FCCP might indirectly cause a release of Ca2+ by lowering hepatic ATP was examined at two levels of organization: 1) in the whole organ, by perfusing livers with fructose, a compound that was shown previously to drastically lower ATP in the liver, and 2) in isolated microsomal vesicles by depleting ATP with glucose and hexokinase. Fructose evoked Ca2+ release from the perfused liver. Similarly, depletion of ATP by the addition of glucose and hexokinase evoked a rapid release of the accumulated Ca2+ from microsomal vesicles probably by the inhibition of the Ca2(+)-ATPase. These results demonstrate that the major mechanism by which FCCP releases Ca2+ in intact cells is by lowering ATP levels.
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PMID:Hormonal stimulation of Ca2+ release from the perfused liver: effects of uncoupler. 210 59

A method was developed for preparation of dansylated derivatives of adenine nucleotides characterized by fluorescence when being irradiated with UV-light. The involvement of dansylated ATP, ADP and AMP as substrate analogues in energy metabolism is demonstrated in the ATPase, hexokinase, pyruvate kinase and adenylate kinase reactions. The kinetics of the reactions is discussed.
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PMID:[Preparation and isolation of dansyladenylates as fluorescent substrates in reactions of the energy metabolism]. 214 Aug 94

The three-dimensional structure of the amino-terminal 44K ATPase fragment of the 70K bovine heat-shock cognate protein has been solved to a resolution of 2.2 A. The ATPase fragment has two structural lobes with a deep cleft between them; ATP binds at the base of the cleft. Surprisingly, the nucleotide-binding 'core' of the ATPase fragment has a tertiary structure similar to that of hexokinase, although the remainder of the structures of the two proteins are completely dissimilar, suggesting that both the phosphotransferase mechanism and the substrate-induced conformational change intrinsic to the hexokinases may be used by the 70K heat shock-related proteins.
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PMID:Three-dimensional structure of the ATPase fragment of a 70K heat-shock cognate protein. 214 60

The gamma-P adduct of ATP with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (ATP-EDC) was synthesized and incubated with the Ca-ATPase of sarcoplasmic reticulum with the result that time-dependent complete loss of the enzyme's activity occurred. The inactivation required calcium and magnesium while ATP had a protective effect. ATP-EDC incubation with the NaK-ATPase and HK-ATPase produced partial (greater than 50%) inactivation, but had no effect on myosin S1, pyruvate kinase and hexokinase, suggesting that this ATP analog is a specific inactivator of the so-called 'P-type' ATPases.
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PMID:Inactivation of Ca2(+)-, Na+K(+)-, and H+K(+)-ATPases with a carbodiimide derivative of ATP. 215 4

Freshly isolated rabbit proximal tubules (PT), confluent primary rabbit proximal tubule cultures (PTC) and LLC-PK1 cells were characterised. Brushborder enzyme activities were lower in PTC than in LLC-PK1: ratios were 0.026 for alkaline phosphatase (AP), 0.458 for alanine aminopeptidase (AAP) and 0.514 for gamma-glutamyl transpeptidase (GGT). PT/PTC ratios were 79.7 for AP, 7.96 for AAP and 3.45 for GGT. Specific activities of hexokinase (HK) and lactate dehydrogenase (LDH) were high in cultured cells as compared to PT: PT/PTC ratios were 0.063 and 0.033, while PTC/LLC-PK1 ratios were 0.406 and 1.19 for HK and LDH respectively. PTC/LLC-PK1 ratios were 2.21 for Na/K ATPase, 2.07 for succinate dehydrogenase, 1.12 for cathepsin B, 0.607 for N-acetyl-beta-D-glucosaminidase and 8.98 for glutathione-S-transferase. Adenylate cyclase response to parathormone (PTH), was similar in PTC and PT, but stimulated/basal ratios were higher in PT than in PTC. LLC-PK1 cells were stimulated by thyrocalcitonin (SCT), arginin-vasopressin (AVP) and PTH; stimulated/basal ratios ranked AVP greater than PTH greater than SCT. Differences between both types of cultures affect the choice of in vitro model for nephrotoxicity studies.
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PMID:Adenylate cyclase responses and biochemical characterization of primary rabbit proximal tubular cell cultures and LLC-PK1 cells. 228 70

KT5926, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3 ,9, 10-tetrahydro-8,11-epoxy, 1H,8H, 11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde] trinden-1-one, was found to be a potent and selective inhibitor of myosin light chain kinase. The compound inhibited both Ca2+/calmodulin-dependent and -independent smooth muscle myosin light chain kinases to a similar extent. The inhibition was not affected by the concentration of calmodulin. Kinetic analyses showed that the mode of inhibition was of the competitive type with respect to ATP (Ki, 18 nM) and of the noncompetitive type with respect to myosin light chain (Ki, 12 nM). These results indicated that KT5926 directly interacted with the enzyme at the catalytic site. KT5926 also inhibited other protein kinases, but with relatively high Ki values; the values for protein kinase C, cAMP-dependent protein kinase, and cGMP-dependent protein kinase were 723, 1200, and 158 nM, respectively. Ca2(+)-ATPase, Na+/K(+)-ATPase, hexokinase, and 5'-nucleotidase were not inhibited by KT5926 at less than 10 microM. The effect of KT5926 on serotonin secretion and protein phosphorylation induced by platelet-activating factor or phorbol ester was examined in rabbit platelets. KT5926 inhibited the phosphorylation of a 20-kDa protein but had no effect on the phosphorylation of a 40-kDa protein, thereby indicating that the compound exerts its selective inhibition of myosin light chain kinase in intact cells. The compound inhibited serotonin secretion induced by platelet-activating factor, but its potency was significantly less than that of K-252a, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9, 10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b, 11a-triazadibenzo[a,g]cycloocta [cde]trinden-1-one, which inhibited the phosphorylation of both the 20-kDa protein and the 40-kDa protein. Phorbol ester-induced secretion was not suppressed by KT5926. These results provide the evidence that both the 20-kDa protein phosphorylation by myosin light chain kinase and the 40-kDa protein phosphorylation by protein kinase C substantially contribute to the secretion response in platelets.
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PMID:KT5926, a potent and selective inhibitor of myosin light chain kinase. 232 35

Many hormonal, neurotransmitter, and sensory stimuli trigger the formation of inositol 1,4,5-trisphosphate, which in turn releases calcium from intracellular stores. We report here that inositol 1,4,5-trisphosphate-induced calcium release from saponin-permeabilized rat basophilic leukemia cells at 37 degrees C is markedly biphasic, in contrast with nearly monophasic release kinetics at 11 degrees C. Hepatoma, PC-12 neuronal cells, and several other cell types exhibit similar biphasic release at 37 degrees C. The biphasic kinetics are not due to degradation of inositol 1,4,5-trisphosphate or to increased Ca2(+)-ATPase pump activity. Biphasic calcium release was also seen when ATP was quenched to less than 0.4 microM by adding hexokinase and glucose, suggesting that phosphorylation is not involved. External calcium (100 nM-600 nM) range had little influence on the biphasic kinetics. Rapid-mixing experiments revealed that rapid efflux of calcium is followed in approximately 0.5 s by a 30-fold slower efflux. Most striking, successive additions of the same amount of inositol 1,4,5-trisphosphate induced short bursts of calcium release of similar size. This retention of responsiveness, which we term increment detection, may be a distinct mode of signal transduction. Like inactivation and adaptation, increment detection gives rise to transient responses to sustained stimuli. Systems exhibiting inactivation, adaptation, and increment detection differ in their responsiveness (none, partial, and full, respectively) to stepwise increases in stimulus intensity. Increment detection could be advantageous in generating receptor-triggered calcium oscillations.
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PMID:Transient calcium release induced by successive increments of inositol 1,4,5-trisphosphate. 233 24


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