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 understanding of the effects of cannabinoids in human subjects has been obscured by a lack of knowledge about how the various active principles from marijuana act at the cellular level in the brain. For this reason the present study was undertaken to determine the effects of cannabinoids on the enzymes associated with the synaptic membranes. Electron micrographic analysis was performed to determine the purity of synaptic membrane preparations from rat brain, and subsequently such preparations were subjected to additions of ethanol, Tween-80, 80% glycerol, and either delta-tetrahydrocannabinol, 11-hydroxy-delta-tetrahydrocannabinol, or cannabinol. Both sodium and potassium activated ATPase (Na, K-ATPase), and Mg-ATPase were measured as the micrometer orthophosphate (P) released per minute per microgram membrane protein and these specific activities of the enzymes expressed as absolute values and as the percentage depression brought about by the cannabinoids. The ATPase spcific activities are taken from the rate curve over a 30-min incubation time. Additionally, synaptic membrane acetylcholineesterase specific activity was measured by continuous rate enzyme assay. While as low as 10 M delta-tetrahydrocannabinol showed appreciable decrements in both the membrane-bound ATPases, the other cannabinoids did not show such a great depression in enzyme activity. The specific activity of acetylcholinesterase, which is weakly bound to the membrane, showed only slight or no changes in activity with the various cannabinoids. It was additionally shown that the cannabinoids, delta-tetrahydrocannabinol in particular, bound to the synaptic membranes almost irreversibly in the in vitro system, and that the vehicle for dissolving the cannabinoids, while used as background control values when calculating the percentage decrements in enzyme specific activity, did vary the effects on the ATPase enzymes in particular. These data are discussed in relation to psychotomimetic activity of the cannabinoids.
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PMID:Effects of cannabinoids on synaptic membrane enzymes. I. In vitro studies on synaptic membranes isolated from rat brain. 14 40

The distribution pattern of marker enzymes (Na, K-ATPase, acetylcholinesterase) in three fractions of synaptic membranes (SM) of rat brain were studied. The effects of three anticonvulsive agents on Na, K-ATPase from the total fraction of rat brain SM and purified membrane preparation from ox brain were estimated by different methods. Under optimal conditions (Na/K = 5) diphenylhydantoin (DPH) at a concentration of 0,1 mM activates Na, K-ATPase from the total SM fraction only in the absence of ouabain, whereas carbamazepine and pyrroxane taken at the same concentrations have no effect on Na, K-ATPase, irrespective of the type of the enzyme assay. DPH seems to compete with ouabain. Under non-optimal ionic conditions (Na/K = 250) all the anticonvulsive substances studied inhibit Na, K-ATPase of the total SM fraction. The mixture of hydrophobic agents (propylene glycol and ethanol) used to dissolve carbamazepine inhibits Na, K-ATPase from the total SM fraction only under non-optimal conditions. The inhibiting effect of the anticonvulsive substances under study on Na, K-ATPase from the purified membrane preparations is maximal at the concentration of 10(-6) M; at higher concentrations the effect is less pronounced.
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PMID:[Effects of anticonvulsive substances on Na,K-ATPase from the synaptic membranes of animal brain]. 14 27

The phospholipid requirement of membrane-bound enzymes may depend on several reasons. In our laboratory we have investigated lipids (1) as a bidimensional medium required for the movement of Coenzyme Q, a lipid-soluble cofactor of the mitochondrial respiratory chain, and (2) as a hydrophobic environment necessary to impose the proper conformation to membrane-bound enzymic proteins. We have found that Coenzyme Q, once reduced by NADH dehydrogenase, must cross the inner mitochondrial membrane; only quinones having long isoprenoid side chains can easily cross phospholipid bilayers, and this is the reason why a short chain quinone such as CoQ-3 inhibits NADH oxidation. The incapability of short quinones to cross lipid bilayers is due to their disposition in the lipid bilayer, stacked within the phospholipids. The conformational role of lipids has been investigated indirectly observing the kinetics of membrane-bound enzymes, e.g. the mitochondrial ATPase, and directly by circular dichroism. Lipid removal or lipid perturbation with organic solvents induce a decrease of alpha-helical content in mitochondrial proteins, and give rise to a series of kinetic changes in ATPase, including uncompetitive inhibition, increased activation energy, and loss of cooperativity in oligomycin inhibition. The recognition of a conformational role of lipids has allowed us to postulate a working hypothesis for the mechanism of action of general anesthetics. Such drugs have been found by us, by means of spin labels and fluorescent probes, to disrupt lipid protein interactions in several membranes, including synaptic membranes. The loosening of such interactions is believed to induce conformational changes, which will alter ion transport systems necessary to the propagation of neural impulses. Conformational changes induced by anesthetics have been found by us both directly by circular dichroism and indirectly by enzyme kinetics. The conformational effect of anesthetics is not directly exerted on the proteins but is mediated through the lipids. In agreement with this hypothesis we have found that membrane-bound acetylcholinesterase is inhibited by anesthetics, whereas the solubilized enzyme is not inhibited. However, binding of the solubilized enzyme to phospholipids restores anesthetic inhibition.
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PMID:Biophysical studies on agents affecting the state of membrane lipids: biochemical and pharmacological implications. 15 58

1. The proportions of both saturated and polyunsaturated fatty acids were measured in the erythrocytes in Cystic Fibrosis (CF) patients along with two membrane bound enzymes ATPase and acetylcholinesterase. Linoleic acid was found to be significantly decreased and arachidonic acid increased in CF patients. The proportion of saturated fatty acids were not significantly different from the controls. Only adenosinetriphosphatase activity was found to be reduced and not acetylcholinesterase in CF patients.
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PMID:A study of erythrocyte fatty acids, adenosinetriphosphatase and acetylcholinesterase in cystic fibrosis. 15 9

A zonal rotor technique for the preparation of synaptosomes in bulk from bovine brain frontal cortex based on an impirical transformation of a small-volume discontinuous sucrose density gradient arrangement is presented in detail. The procedure yields new information concerning synaptosomes prepared in sucrose gradients. Cerebroside analysis and electron microscopy show myelin contamination to be restricted to the leading, less dense edge of the synaptosomal profile, free mitochondria to the trailing, more dense edge. Exclusion of fringe areas yields a highly purified synaptosome preparation which entirely enters the next dense layer beyond the 0.8 : 1.2 M sucrose interface. This interface collects most of the oubain-sensitive (Na+, K+) adenosine triphosphatase activity. The purified synaptosomes display very high intrinsic sialidase activity and are rich in di-, tri-, and tetrasialogangliosides, the preferred substrates for the enzyme. Up to 90% of the cholinesterase activity in the zonal rotor synaptosome preparation is specific acetylcholinesterase.
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PMID:Large-scale preparation of synaptosomes from bovine brain using a zonal rotor technique. 15 41

Cardiotoxin isolated from Naja mossambica mossambica selectively deactivates the sodium-potassium activated adenosine triphosphatase of axonal membranes. Tetrodotoxin binding and acetylcholinesterase activities are unaffected by cardiotoxin treatment. The details of association of cardiotoxin with the axonal membrane were studied by following the deactivation of the sodium-potassium activated adenosine triphosphatase and by direct binding measurements with a tritiated derivative of the native cardiotoxin. The maximal binding capacity of the membrane is 42-50 nmol of cardiotoxin/mg of membrane protein. The high amount of binding suggests association of the toxin with the lipid phase of the membrane. It has been shown that cardiotoxin first associates rapidly and reversibly to membrane lipids, then, in a second step, it induces a rearrangement of the membrane structure which produces and irreversible deactivation of the sodium-potassium activated adenosine triphosphatase. Solubilization of the membrane-bound ATPase with Lubrol WX gives an active enzyme species that is resistant to cardiotoxin-induced deactivation. Cardiotoxin binding to the membrane is prevented by high concentrations of Ca 2+ and dibucaine. Although cardiotoxins and neurotoxins of cobra venom have large sequence homologies, their mode of action on membranes is very different. The cardiotoxin seems to bind to the lipid phase of the axonal membrane and inhibits the sodium-potassium activated adenosine triphosphatase, whereas the neurotoxin associates with a protein receptor in the post-synaptic membrane and blocks acetylcholine transmission.
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PMID:Molecular mechanism of cardiotoxin action on axonal membranes. 18 4

The histochemical localization of carbohydrates, ribonucleoproteins (RNA), lipids, some hydrolytic enzymes, succinate and lactate dehydrogenase and acetylcholinesterase were investigated in the prostate, urethral and bulbourethral glands of the camel. These glands probably secrete carbohydrate-protein complexes. In the bulbourethral glands, they are sulphated mucopolysaccharides. RNA was seen in the cytoplasm of the prostate and urethral glands. Neutral lipids were cytoplasmic and present in moderate amounts in the prostate and urethral glands and in traces, in the bulbourethral gland. Acid phosphatase-containing granules were abundant in the prostate, moderate in the urethral glands and in traces in the bulbourethral glands. Alkaline phosphatase was observed in the apical cytoplasm of the prostate and bulbourethral glands and in the ducts of the urethral glands. ATPase and adenosine 5-monophosphatase were seen in the basal laminae and interstitial tissue. In the urethral glands, adenosine 5-monophosphatase was distributed diffusely in the cytoplasm. Succinate dehydrogenase was seen in the urethral and bulbourethral glands. Varying degrees of lactate dehydrogenase activity was observed in all the glands. Acetylcholinesterase was confined to neural elements. The pars disseminata and the urethral glands were considered as two distinct glandular zones along the pelvic urethra. The significance of these histochemical results is discussed.
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PMID:Some histochemical studies on the prostate, urethral and bulbourethral glands of the one-humped camel (Camelus dromedarius). 18 43

Membrane preparations of erythrocytes from normal and P. chabaudi-infected mice and membrane preparations of P. chabaudi-infected and uninfected erythrocytes from infected mice and separated by zonal centrifugation were characterized by the pattern of proteins and extracted glycoproteins obtained by SDS-polyacrylamide gel electrophoresis and by the specific activities of membrane associated enzymes. The protein pattern of the membrane preparation of infected erythrocytes showed similar differences from membrane preparations of normal erythrocytes as those described by Weidekamm et al. for P. berghei. The pattern of glycoproteins extracted by the chloroform-methanol method showed characteristic differences as compared to the controls. A new band (PASi) with a molecular weight of about 165,000 corresponds with the protein band IIa. In membrane preparations of normal erythrocytes and of nonparasitized erythrocytes separated from parasitized erythrocytes by zonal centrifugation was no difference in specific activities of ATPase, adenylate kinase and acetylcholinesterase. Adenylate kinase activity was markedly increased and acetyl-cholinesterase activity was slightly increased in membrane preparations of infected cells. Specific activities of ATPase of membrane preparations of normal and parasitized erythrocytes did not show significant differences. There was a decrease in enzyme activity of ATPase and an increase of acetylcholinesterase in Triton X 100 containing samples. Specific activities of an acid phosphatase were lower in membrane preparations of parasitized cells than in the controls.
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PMID:Plasmodium chabaudi-infection of mice: specific activities of erythrocyte membrane-associated enzymes and patterns of proteins and glycoproteins of erythrocyte membrane preparations. 19 21

Activity of Na, K -ATPase, acetylcholinesterase (AChE) and glutamic acid decarboxylase (GAD) in the fractions of the rat brain and spinal cord tissue were studied in rats during a single electroshock (ES) and 5 and 30 minutes after it. GAD activity of the synaptosome fraction was shown to decrease insignificantly, but activity of AChE, Na, K -ATPase and possibly of proteolytic enzymes increased 5 minutes after electroshock and became normal in 30 minutes. It is supposed that the revealed inhibition of Na, K -ATPase activity in the "synaptosomes" of the rat brain cortex could be of pathogenetic significance in the origination of the convulsive process.
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PMID:[Activity of Na, K-ATPase and the enzymes of intermediate metabolism in the brains of rats exposed to electroshock]. 21 Aug 59

Dopa-decarboxylase, acetylcholinesterase, sodium plus potassium stimulated adenosine triphosphatase (Na+ + K+-ATPase), and membrane-bound protein kinase were compared in the erythrocytes of patients with Huntington's disease and normal controls. All these enzymes also exist in the basal ganglia. The Na+ +K+-ATPase level was elevated (p less than 0.05) in Huntington's disease, while no significant changes were observed in the other enzymes. This finding is consistent with the concept that Huntington's disease is associated with a general membrane abnormality.
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PMID:Increased sodium plus potassium adenosine triphosphatase activity in erythrocyte membranes in Huntington's disease. 21 30


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