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)

Since we had shown recently that fatty acyl-CoA derivatives stimulate (Na+ + K+)-ATPase activity at suboptimal ATP concentrations, we used sealed vesicles of beef heart sarcolemma to examine the effects of these compounds on the transport function of the enzyme. The sodium pump was detected in inside-out vesicles as a component of Na+ uptake that was dependent on intravesicular (extracellular) K+ and extravesicular (intracellular) ATP and was sensitive to vanadate and digitoxigenin. The pump flux was stimulated without a lag by palmitoyl-CoA (K0.5 = 3 microM) when ATP concentration was 50 microM, but not when it was 2 mM. Saturating palmitoyl-CoA reduced the K0.5 of ATP for the pump by a factor of 3-6. Raising the intracellular K+ concentration increased the K0.5 of ATP, and this effect of K+ was antagonized by palmitoyl-CoA. At concentrations up to 0.5 mM, palmitoyl-CoA had no effect on ATP-independent (passive) Na+ uptake. All tested long-chain acyl-CoA derivatives had effects similar to that of palmitoyl-CoA; but CoA, acetyl-CoA, and palmitic acid were ineffective. Palmitoyl carnitine and docosahexanoic acid, amphiphilic compounds with inhibitory and biphasic effects on the hydrolytic activity of purified (Na+ + K+)-ATPase, had purely inhibitory effects on the pump at high concentrations that also affected the passive fluxes. The data support the proposition that fatty acyl-CoA derivatives mimic the effect of ATP at a regulatory site and suggest that these intracellular liponucleotides may be involved in the control of the pump.
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PMID:Control of cardiac sodium pump by long-chain acyl coenzymes A. 243 66

1. Beating of aggregates of embryonic chick myocytes, in primary culture, was quantified by use of a motion-detector and video-recorder technique. Interactions of palmitoyl carnitine, a putative endogenous ligand at Ca2+ channels, with calcium antagonists were investigated. 2. Bay K 8644 (1-100 nM) and palmitoyl carnitine (0.2-30 microM) increased edge movement of the aggregates; beats fused so that there was an increase in baseline 'tone'. The concentrations required to produce a 50% increase in edge movement were 2.5 nM for Bay K 8644 and 2 microM for palmitoyl carnitine. Higher concentrations (20-30 microM) of palmitoyl carnitine caused tachycardia of abrupt onset but resulted in cessation of beating. The effects of palmitoyl carnitine were not stereo-selective in that the (+)- and (-)-isomers were equieffective. Lysophosphatidyl choline (LPC) had no effect in concentrations up to 10 microM but higher concentrations caused tachycardia followed by cessation of beating. High concentrations of both palmitoyl carnitine and LPC (100 microM) caused break-up of the aggregates, presumably as a result of detergent effects. 3. Palmitoyl carnitine (1-100 microM) reversed the inhibitory effects of nisoldipine (0.3 microM), diltiazem (10 microM) and verapamil (1 microM). Ouabain was ineffective in reversing the effects of nisoldipine, differentiating the effects of palmitoyl carnitine from those of Na+/K+ ATPase inhibition. In contrast, palmitoyl carnitine did not reverse the inhibitory effects of pimozide (2 microM) or lidoflazine (7 microM); palmitoyl carnitine showed a similar profile to Bay K 8644 in this respect. 4. These findings indicate that the effects of palmitoyl carnitine closely resemble those of Bay K 8644 and can be differentiated from those of lysophospholipids. As palmitoyl carnitine accumulates in the sarcolemma during myocardial ischaemia, the mode of action in the Ca2 + channel may have clinical relevance for the use of calcium antagonists in ischaemia.
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PMID:Interaction of palmitoyl carnitine with calcium antagonists in myocytes. 247 46

Native sarcolemma (SL) from adult canine cardiac myocytes (Na+-K+-ATPase activity 74.2 +/- 3.0 mumol X mg-1 X h-1) was preincubated (10 min, 37 degrees C, pH 7.2) with 1) 20-600 microM palmitoyl carnitine, 2) 250 nM-2.5 mM propranolol, or 3) 20-600 microM palmitoyl carnitine plus propranolol at various concentrations (0.0, 0.025, 0.25, 0.5, 1.0, and 2.5 mM); after preincubation, Na+-K+-ATPase activity was assayed. Palmitoyl carnitine alone (series 1) had no effect on ATPase activity over the range of 20-400 microM but was inhibitory (30%) at 600 microM. Propranolol alone (series 2) did not alter ATPase activity at any concentration. When SL membranes were exposed to both palmitoyl carnitine and propranolol (series 3), a dose-dependent inhibition of ATPase activity was observed. The inhibitory effect was not reversed by 3.0% bovine serum albumin. Propranolol concentrations greater than 0.025 mM significantly inhibited the activity of SL exposed to palmitoyl carnitine (above 150 microM). Palmitoyl carnitine and propranolol do not have to be added simultaneously to produce combined inhibition. Activity was inhibited 50% when SL were pretreated with 100 microM palmitoyl carnitine followed by addition of 2.5 mM propranolol no inhibition occurred if preincubation conditions were reversed. Thus exposure of SL to propranolol and reported physiological levels of palmitoyl carnitine leads to irreversible inhibition of the Na+-K+-ATPase, which may be due to the combined membrane-perturbant actions of these amphipathic agents.
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PMID:Inhibition of sarcolemmal Na+-K+-ATPase by palmitoyl carnitine: potentiation by propranolol. 298 78

Long-chain unsaturated fatty acids and fatty acyl CoA derivatives activated (Na++K+)-ATPase at suboptimal, but not optimal, ATP concentrations. Activation was obtained within a narrow range of fatty acid concentrations; higher acid levels inhibited the enzyme. The various CoA esters, however, activated with K0.5 values in the range of 0.15-10 microM; and with no inhibitory effects at concentrations up to 100 microM. Palmitoyl CoA, binding reversibly to a regulatory site, reduced K0.5 of ATP from 0.37 mM to 0.17 mM; and changed the Hill coefficient of the substrate-velocity curve from 0.86 to 0.63. These compounds may be physiological regulators that desensitize the function of this enzyme to diminishing ATP levels.
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PMID:Activation of (Na++K+)-ATPase by long-chain fatty acids and fatty acyl coenzymes A. 301 98

We have previously reported that palmitoyl carnitine is a potent inhibitor of Na+-K+-ATPase. Recently, Owens et al. [Am. J. Physiol. 242 (Heart Circ. Physiol. 11): H456-H461, 1983] reported that palmitoyl carnitine did not inhibit Na+-K+-ATPase activity of their cardiac sarcolemmal preparation that had been isolated without the use of detergents. We have investigated this using a similar preparation. Palmitoyl carnitine appears to be a much less effective inhibitor of the sarcolemmal preparation at lower concentrations because it simultaneously stimulates Na+-K+-ATPase by unmasking latent activity. When this latent activity is exposed by pretreatment with sodium dodecyl sulfate, a marked inhibition by palmitoyl carnitine is then observed. Similar results were obtained with lysophosphatidylcholine (LPC). The concentrations of palmitoyl carnitine and LPC required to inhibit Na+-K+-ATPase are, however, higher than those that cause sarcolemmal permeability changes; consequently, it is improbable that inhibition of the enzyme by these metabolites occurs to any significant extent in vivo.
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PMID:Effects of palmitoyl carnitine and LPC on cardiac sarcolemmal Na+-K+-ATPase. 609 98

Palmitoyl CoA inhibited EDTA-ATPase of heavy meromyosin (HMM) prepared from rabbit skeletal muscle. The concentration for half maximum inhibition of EDTA-ATPase was about 18 microM. Myristoyl CoA, the other long chain fatty acyl CoA, also inhibited EDTA-HMM ATPase, but CoA and short chain CoA thioesters, such as butyryl CoA, acetoacetyl CoA and acetyl CoA, at 40 microM hardly inhibited EDTA-ATPase. Less than 20% inhibition of EDTA-HMM ATPase was obtained with Na-palmitate and Na-myristate at 40 microM, whereas about 90% inhibition of the enzyme occurred in the presence of 40 microM palmitoyl CoA and myristoyl CoA. Palmitoyl carnitine, as well as carnitine, failed to inhibit EDTA-HMM-ATPase. The inhibition of palmitoyl CoA of EDTA-ATPase was reversed by bovine serum albumin and spermine. Mg2+-HMM ATPase activity was enhanced by palmitoyl CoA at 2, 5, and 10 microM. About a 25% increase in Mg2+-HMM ATPase activity was obtained at 5 and 10 microM. At higher concentrations than 20 microM, the enzyme was inhibited by palmitoyl CoA and the degree of inhibition was related to the concentration of the CoA thioester. At 80 microM, the activity was about 15% of the maximum value. The efficacy of myristoyl CoA on Mg2+-ATPase was almost the same as that of palmitoyl CoA. Mg2+-ATPase activity was not enhanced by CoA, butyryl CoA, acetoacetyl CoA, Na-myristate, Na-palmitate, palmitoyl carnitine, or carnitine at 10 microM, and was hardly reduced by these substances at 40 microM. Serum albumin and spermine also canceled, to some extent, these effects of palmitoyl CoA on Mg2+-ATPase.
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PMID:Inhibition of palmitoyl CoA of EDTA- and Mg2+-ATPase of heavy meromyosin from rabbit skeletal muscle. 611 60

ATPase of 14S dynein, extracted from spermatozoa of the sea urchin, Hemicentrotus pulcherrimus, and partially purified by sucrose density gradient centrifugation, was inhibited non-competitively by palmitoyl CoA at concentrations higher than 20 microns, and was stimulated at concentrations between 2 microns and 10 microns. The effects of palmitoyl CoA on dynein ATPase were reversed by bovine serum albumin (1 mg/ml) and spermine (0.1 and 1 mM). Myristoyl CoA exerted effects similar to those of palmitoyl CoA. Short chain fatty acyl CoAs, such as butyryl CoA, propionyl CoA and acetyl CoA, CoA, Na-palmitate, Na-myristate, and palmitoyl carnitine had hardly any effect on dynein ATPase. Palmitoyl CoA failed to inhibit purified CF1 ATPase from chloroplasts of spinach, ATPase of rat liver mitochondria and alkaline phosphatase from calf intestine.
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PMID:Inhibition by palmitoyl CoA of dynein ATPase from sea urchin spermatozoa. 621

The effect of amphiphilic lipid intermediates on the Na+-stimulatable activity of the Na+-K+-ATPase of sarcolemma from adult canine cardiac myocytes was studied. Sarcolemma (mean Na+-stimulatable ATPase activity of 73 mumol.mg sarcolemmal protein-1.h-1) was preincubated (37 degrees C for 10 min at pH 7.2) or rapidly mixed at 0 degrees C with amphiphilic lipid intermediates prior to dilution and assay of enzyme activity. Their effects were dependent on temperature, initial concentration, and the ratio of bound amphiphile to sarcolemmal protein. In particular, pretreatment of freshly prepared sarcolemma at 0 degrees C with arachidonyl CoA (up to 0.25 mM) caused 110% stimulation above control activity; palmitoyl CoA or palmitoyl carnitine under the same conditions caused no significant effect. Despite strong binding to the sarcolemmal vesicles, palmitoyl carnitine (up to 0.4 mM or 5 mumol/mg protein) and palmitoyl CoA (0.1 mM or 1.0 mumol of membrane-bound palmitoyl CoA/mg protein) were ineffective even with preincubation. Palmitoyl CoA was inhibitory above this level. Preincubation (22 degrees C for 10 min) with lysophosphatidylcholine only produced inhibition (40% at 0.75 mM). Thus fatty acyl thioesters of CoA and lysophosphatidyl choline but not palmitoyl carnitine perturb sarcolemmal Na+-K+-ATPase activity.
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PMID:Effects of fatty acid intermediates on Na+-K+-ATPase activity of cardiac sarcolemma. 627 56

Palmitoyl coenzyme A (PCoA) inhibits Ca2+ uptake and stimulates Ca2+-activated ATPase in sarcoplasmic reticulum vesicles. The inhibitory effect on Ca2+-uptake is referable to a stimulation of Ca2+ release which is directly correlated to the concentration of PCoA added. The comparison of the Ca2+-releasing effect of PCoA in different experimental conditions indicates that concentrations of PCoA higher than 10 microM may be disruptive for the vesicles while concentrations of PCoA lower than this value can activate a Ca2+-releasing channel or more generally can increase the membrane permeability for Ca2+.
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PMID:Effects of palmitoyl coenzyme A on rat skeletal muscle sarcoplasmic reticulum. 631 44

1. In birds, prolonged cold exposure induces the development of a non-shivering thermogenesis (NST) of muscular origin that may result from an increase in ATP-dependent cycling of Ca2+ between the sarcoplasmic reticulum (SR) and the cytosol. 2. Because fatty acids are thought to play a significant role in NST, we investigated the effects of palmitic acid and related metabolites on skeletal SR Ca2+ uptake and release in ducklings. 3. Ca(2+)-ATPase activity, 45Ca2+ release and [3H]ryanodine-binding measurements indicated that palmitic acid was without effect on the Ca(2+)-ATPase and Ca2+ release channel. Palmitoyl carnitine and palmitoyl coenzyme A inhibited the Ca(2+)-ATPase at concentrations > 20 microM whereas both activated the Ca2+ release channel at concentrations < or = 20 microM in a dose-dependent manner. 4. Palmitoyl carnitine stimulated [3H]ryanodine binding to skeletal but not cardiac SR vesicles. Induction of 45Ca2+ release was observed with long-chain (C > or = 14) but not with short-chain acyl carnitines (C < or = 12). 5. Long-chain acyl carnitines accumulated significantly in duckling skeletal muscle during cold acclimation. Accordingly, these results suggest that long-chain acyl metabolites may modulate SR Ca2+ cycling and its associated thermogenesis in vivo.
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PMID:Effects of palmitoyl carnitine and related metabolites on the avian Ca(2+)-ATPase and Ca2+ release channel. 799 33


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