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:3.6.4.1 (myosin ATPase)
1,140 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contraction-relaxation coupling was studied in rat and guinea-pig papillary muscles during chronic pressure overload induced by aortic stenosis and during acute hypoxia. Coefficient R1 (ratio between maximum shortening and lengthening velocities of the isotonic twitch loaded with preload only) and coefficient R2 (ratio between the positive and negative peak force derivatives of the isomeric twitch) tested the contraction-relaxation coupling under low and heavy load respectively. Cardiac hypertrophy was similar in guinea-pigs (+43 +/- 5%) and rats (+55 +/- 7%). In both species, cardiac hypertrophy significantly impaired contraction and relaxation phases. In the rat, neither R1 (-1 +/- 4%) nor R2 (-5 +/- 4%) varied significantly during cardiac hypertrophy whereas, in the guinea-pig, an increase in R1 (+56 +/- 18%), P less than 0.001) and in R2 (+26 +/- 9%, P less than 0.01) was noted. These species-related differences might be linked in part to differences in sarcoplasmic reticulum function and myosin ATPase activity. Acute hypoxia, which leads to a decrease in cellular ATP levels, was responsible for a marked decrease in myocardial performance, while R1 increased (+66 +/- 8%, P less than 0.05) and R2 decreased (-14 +/- 1%, P less than 0.05). These results showed that chronic pressure overload modified the contraction-relaxation coupling in a characteristic manner according to the species studied and these changes differed from those observed during acute hypoxia.
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PMID:The contraction-relaxation coupling during pressure-induced cardiac hypertrophy. 215 36

After reviewing the controversies in the literature surrounding the regulation of oxidative phosphorylation, a unifying theory to integrate the disparate results would be welcome. Following the traditional biochemical approach to identifying sites of control, one searches for the rate-limiting step in a series of reactions (i.e. a biochemical pathway) that, presumably, will not be at equilibrium. This approach has not succeeded in locating a reaction in cardiac respiratory control that is singularly rate-limiting and may actually be contributing to, rather than clarifying, the problem. There are two major criticisms of this approach. First, even if the step is in disequilibrium, it does not prove that it is rate-limiting (26). Second, a reaction near equilibrium can contribute to regulation of a system (37). In a complex, multiple-reaction integrated pathway such as mitochondrial respiration there are many steps that could potentially share the control of the overall system. Thus this pathway easily lends itself to the possibility of multiple sites of control, each of which could contribute by varying degrees to regulation. In Figure 3 we present one possible network (undoubtedly incomplete) for the distributed control of respiration, which incorporates contributions by the cellular redox state (supply), phosphate metabolite concentrations (either kinetic or thermodynamic), and oxygen. The coordination of the dehydrogenases, phosphate metabolites, and myosin ATPase activity (work) may be orchestrated by a second messenger. Calcium is an attractive candidate for this role (15) as it simultaneously can modulate reducing equivalent supply via the dehydrogenases and ATP use by the myofibrils. The theory of shared control along the path of respiration is not new (37), and has been gaining support from a variety of laboratories (3, 9, 26). Applying this concept to the experimental setting, the relative control strengths for various steps in oxidative phosphorylation have been reported for isolated mitochondria (26). The control coefficients for respiration in isolated myocytes or hearts in vivo remain unknown at this time. If control of respiration occurs at multiple sites, it could account for much of the disagreement in the literature. Experimental conditions, whether intentional or inadvertent, that saturate one or more control mechanisms will increase the relative effect of the other regulatory sites on the remaining range of mitochondrial function. If, for example, the medium surrounding isolated myocytes is such that the cytosolic redox state and pO2 are very high, the phosphate metabolite concentrations could logically be expected to be a major factor influencing the observed rate of oxidative phosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Control of mitochondrial respiration in the heart in vivo. 215 67

Thyroid hormone-induced changes in cardiac function have been recognized for over 150 years; however, the biochemical basis of triiodothyronine (T3) action in the heart has been intensely investigated only during the last two decades. T3-induced changes in cardiac function can result from direct or indirect T3 effects. Direct T3 effects result from T3 action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T3 effects, which occur independent of nuclear T3 receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T3 effects are mediated by the binding of T3 to specific nuclear receptor proteins, which results in increased transcription of T3-responsive cardiac genes. The T3 receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. The c-erb A protein is the cellular homologue of the viral erythroblastosis A (v-erb A) protein, which causes red cell leukemia in chickens. Currently, three T3-binding isoforms of the c-erb protein and two non-T3-binding nuclear proteins that exert positive and negative effects on T3-responsive cardiac genes have been identified. T3 increases the heart transcription of the myosin heavy chain (MHC) alpha gene and decreases the transcription of the MHC beta gene, leading to an increase of myosin V1 and a decrease in myosin V3 isoenzymes. Myosin V1, which is composed of two MHC alpha, has a higher myosin ATPase activity than myosin V3, which contains two MHC beta. The globular head of myosin V1, with its higher ATPase activity, leads to a more rapid movement of the globular head of myosin along the thin filament, resulting in an increased velocity of contraction. T3 also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum (SR). This T3 effect results from T3-induced increases in the level of the mRNA coding for the SR calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the SR. Overall, thyroid hormone leads to an increase in ATP consumption in the heart. In addition, less chemical energy of ATP is used for contractile purposes and more of it goes toward heat production, which causes a decreased efficiency of the contractile process in the hyperthyroid heart.
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PMID:Biochemical basis of thyroid hormone action in the heart. 218 6

A modified ATPase method for the simultaneous demonstration of capillaries and fiber types in skeletal muscle is presented. Muscle biopsies were obtained from mice, hamsters, rats, cats, and dogs, quick frozen, and sectioned at 8 microns in a cryostat. The frozen slides were fixed in a neutral formalin solution at 4 C for 5 min, and then incubated at 37 C for 1 hr in a medium containing ATP, Pb2+, and Ca2+ in a tris-maleate buffer (pH 7.2). Dilute (NH4)2S was used as a developer. To test the reliability of the proposed method, serial sections of each biopsy were stained separately for capillaries (amylase-PAS method) and for fiber types by a standard myosin ATPase (m-ATPase) method. Fiber type percent and capillary parameters were determined for each biopsy. No difference in results was observed for parameters determined using the modified ATPase method compared to the standard capillary and fiber type staining methods. This modified technique is therefore suitable for the simultaneous demonstration of capillaries and fiber types in skeletal muscle.
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PMID:A histochemical method for the simultaneous demonstration of capillaries and fiber type in skeletal muscle. 244 Jan 55

Gingerol, isolated as a potent cardiotonic agent from the rhizome of ginger, stimulated the Ca2+-pumping activity of fragmented sarcoplasmic reticulum (SR) prepared from rabbit skeletal and dog cardiac muscles. The extravesicular Ca2+ concentrations of the heavy fraction of the fragmented SR (HSR) were measured directly with a Ca2+ electrode to examine the effect of gingerol on the SR. Gingerol (3-30 microM) accelerated the Ca2+-pumping rate of skeletal and cardiac SR in a concentration-dependent manner. The rate of 45Ca2+ uptake of HSR was also increased markedly by 30 microM gingerol without affecting the 45Ca2+ efflux from HSR. Furthermore, gingerol activated Ca2+-ATPase activities of skeletal and cardiac SR (EC50, 4 microM). The activation of SR Ca2+-ATPase activity by gingerol (30 microM) was completely reversed by 100-fold dilution with the fresh saline solution. Kinetic analysis of activating effects of gingerol suggests that the activation of SR Ca2+-ATPase is uncompetitive and competitive with respect to Mg . ATP at concentrations of 0.2-0.5 mM and above 1 mM, respectively. Kinetic analysis also suggests that the activation by gingerol is mixed-type with respect to free Ca2+ and this enzyme is activated probably due to the acceleration of enzyme-substrate complex breakdown. Gingerol had no significant effect on sarcolemmal Ca2+-ATPase, myosin Ca2+-ATPase, actin-activated myosin ATPase and cAMP-phosphodiesterase activities, indicating that the effect of gingerol is rather specific to SR Ca2+-ATPase activity. Gingerol may provide a valuable chemical tool for studies aimed at clarifying the regulatory mechanisms of SR Ca2+-pumping systems and the causal relationship between the Ca2+-pumping activity of SR and muscle contractility.
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PMID:Gingerol, a novel cardiotonic agent, activates the Ca2+-pumping ATPase in skeletal and cardiac sarcoplasmic reticulum. 244 70

We have measured the rate constant for ATP release from myosin heads of Ca2+-activated, demembranated muscle fibers using the technique of phosphate-water oxygen exchange. Single rabbit psoas fibers were held in an activating solution in [18O]water ([MgATP] = 8 mM, ionic strength = 0.2 M, pH = 7.0, 24 degrees C). After about 20% hydrolysis of ATP, product Pi and remaining ATP were isolated, and the distribution of 18O in both molecules was analyzed using a mass spectrometer. The exchange in Pi was similar to that previously reported (Hibberd, M. G., Webb, M. R., Goldman, Y. E., and Trentham, D. R. (1985) J. Biol. Chem. 260, 3496-3501). The amount of 18O in ATP gave a rate constant of about 4 s-1 for ATP release, if it is assumed that each rate constant in the pathway of ATP hydrolysis has the same value for all myosin ATPase sites. However, the distribution of 18O in both released Pi and ATP is not well explained by a single pathway for ATP hydrolysis. We present a model that indicates how such distributions could arise from a range of values for the rate constants for Pi and ATP release from actomyosin, and this range is determined by differences in the amounts of strain in attached crossbridges. The kinetic information obtained from these isotope exchange experiments is compared to show that they give a compatible set of rate constants for actomyosin in fibers.
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PMID:Measurement of the reversibility of ATP binding to myosin in calcium-activated skinned fibers from rabbit skeletal muscle. Oxygen exchange between water and ATP released to the solution. 252 91

To test the possibility that ATP diffusion limits the kinetics of myosin ATPase (EC. 3.6.1.3) in situ, myosin was covalently bound to the surface of 2 kinds of films: collagen and Immunodyne. On collagen films, it was bound either with 1-ethyl-3 (3 dimethyl-aminopropyl)carbodiimide (EDC) or with dimethyl-3,3'-dithiobis(propionimidate) (DTP). The apparent Km for K+-ATP rose from 0.26 mM for free myosin in solution to 2-5 mM for covalently bound myosin, and maximum K+-ATPase activity was very low. With the other film, Immunodyne from Pall, the maximum activity of bound myosin was 170 nmol per min per 1.5 cm2 film. The apparent Km for K+-ATP was 2.1 mM when the incubation mixture was vigorously stirred, and the effect of stirring indicated that the kinetics of K+-ATP hydrolysis are limited by external diffusion. The large amount of myosin bound per unit of Immunodyne film surface permitted the study of Mg2+-ATPase activity, although it was 400-500 times less than the K+-ATPase activity. The apparently non-Michaelian kinetics of Mg2+-ATP hydrolysis are attributable to the external diffusion. The apparent Michaelis constant observed at low Mg2+-ATP concentrations rose from 0.27 microM for myosin in solution to 5 microM for myosin bound to Immunodyne film.
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PMID:Diffusion-limited kinetics of immobilized myosin ATPase. 252 82

Three kinds of ATP analogues were synthesized. These ATP analogues can be classified into two conformations, i.e. syn and anti forms with respect to the N-glycosidic bond between adenine and ribose groups of ATP. 3'-O-(N-Methylanthraniloyl)-2-azidoadenosine 5'-triphosphate (MantN2(3)ATP) is recognized as the anti form, as ATP, and the other two, 3'-O-(N-methylanthraniloyl)-8-azidoadenosine 5'-triphosphate (MantN8(3)ATP) and 1,N6-etheno-8-azidoadenosine 5'-triphosphate (epsilon N8(3)ATP) are both syn forms. Mant and etheno groups are both fluorescent which allows detection of their binding to proteins. The photochemical binding of azido groups in ATP analogues to the myosin active site, examined in the presence and absence of ATP, showed that all the analogues bound to the site of myosin ATPase. These analogues also acted as substrates of the ATPase and were hydrolyzed in the active site, as judged by competitive inhibition of the ATPase and by their ATPase activities. Of these analogues, MantN2(3)ATP is very similar to ATP in divalent-cation dependence of its hydrolysis rate and in its ability to trap ADP in the active site with vanadate, while the other two are different from ATP in these respects. The photochemical binding sites of ATP analogues were localized by gel electrophoresis of trypsinized myosin ATPase with photocross-linked ATP analogues and/or by isolating the modified peptides. MantN2(3)ATP was found in the 23-kDa fragment which has a structure common to ATP-binding proteins, i.e. Gly-Xaa-Xaa-Gly-Xaa-Gly-Lys-Thr. Mant N8(3)ATP was found in a region of the 20-kDa fragment where actin is reported to attach.
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PMID:Localization of the ATP-binding site in the 23-kDa and 20-kDa regions of the heavy chain of the skeletal muscle myosin head. 252 53

The effect of an affinity modifier of myosin ATPase representing a mixed anhydride of AMP and mesitylene carboxylic acid (AMP-MA) on myosin with protected active centers was studied. The protection of active centers was performed by the method of Wells et al. Which consists in the stabilization of the myosin-MgADP complex in the enzyme active center by way of cross-linking of the active center with a Co-phenanthroline complex simultaneously interacting with two SH-groups of the protein. Myosin with protected active center completely loses its ability to hydrolyze ATP; however, it can be reactivated by way of SH-group reduction with a subsequent MgADP release from the active centers. Treatment of myosin with protected active centers with AMP-MA does not result in the reduction of the enzyme activity after removal of the Co-phenanthroline complex. This suggests that the irreversible inhibition of myosin ATPase by AMP-MA occurs due to the protein modification outside the active center(s), which provides support for our earlier made conclusion concerning the existence of an additional (with respect to active centers) substrate-binding site in the myosin molecule.
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PMID:[Affinity modification of myosin with protected active centers: confirmation of the existence of an allosteric substrate-binding segment]. 253 15

Quantitative analyses of ATP hydrolysis coupled to movement of eukaryotic flagella is important for understanding the relationship between ATP hydrolysis and movement. The difference in ATPase activity between intact motile axonemes (that is the cytoskeletal core of flagella) and homogenized or immotile axonemes has been assumed to be coupled to movement. However, recent findings on rates of steps in the dynein ATPase cycle and the effect of interaction with microtubules on those steps call for reassessment of movement-coupled ATPase. From these studies, it is clear that dynein ATPase activity is not as tightly coupled to interaction with microtubules as myosin ATPase activity is coupled to interaction with actin. The method by which axonemal movement is inhibited will critically affect the interpretation of difference in ATPase activity. If the homogenization or similar methods uncouple dynein, the difference in ATPase activity is not a useful measurement. Greater understanding of the relationship between dynein kinetics and axonemal movement may be obtained by use of conditions and substrates with known effects at specific steps in the dynein mechanochemical cycle and quantitating their effects on movement.
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PMID:Mechanochemical coupling in eukaryotic flagella. 253 74


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