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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interaction of usual effectors with acetylcholinesterase (EC 3.1.1.7) from bovine erythrocytes was examined under conditions of high ionic strength (gamma/2 greater than or equal to 0,1). Detailed kinetic investigation of the hydrolysis of acetylcholine by acetylcholinesterase in the presence of modifiers shows that the effects produced by numerous quaternary nitrogen compounds on the enzyme can be explained on the basis of binding of the effectors to the anionic subsite of the active center. The various kinetic behaviors, that are observed, are dependent on the relative values of the deacetylation rate constant ak of the complex acetylated enzyme-modifier and of the rate constant k-2 defined by : (see article) with respect to the value of the deacetylation rate constant K of the acetylated enzyme. If a identical to [1--(k/k-2)]-1, it is shown that interaction of the enzyme with tetraethylammonium, pentamethonium, hexamethonium and gallamine ions is characterized by : a greater than a and k-2 greater than k therefore, these modifiers accelerate deacetylation. On the other hand, inhibition of acetylcholinestase by methylpyridinium, d-tubocurarine, tetra-n-propylammonium, tetra-n-butylammonium, decamethonium and succinylbischoline is consistent with one of the conditions : a less than a and k-2 greater than or equal to k or a greater than a and k-2 less than k and inhibition by tetramethylammonium, phenyltrimethylammonium, 3-hydroxyphenyl-triethylammonium, N-methylacridinium and bis (3-aminopyridinium)-1,10-decane ions agrees with one of the two previous conditions or with : (see article) consequently, the effect of these ligands on the deacetylation step is undetermined. However, the effects of choline chloride, thiazinamium methyl sulfate and thioridazine hydrochloride are not entirely consistent with this mechanism but support the existence of a functional peripheral anionic site which is distinct from the anionic subsite of the active center.
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PMID:[Acetylcholinesterase. II. Experimental aspects of interaction with reversible effectors under conditions of high ionic strength]. 0 54

Cholinesterase activities in the hearts and ganglia of an oyster (Crassostrea virginica) and a venerid clam (Macrocallista nimbosa) were measured and compared. Tissue extracts were partially purified by ammonium sulfate fractionation followed by gel column chromatography. Enzymatic activity was assayed spectrophotometrically; substrates were acetyl-, butyryl-, and propionylthiocholine (ATC, BTC, PTC). Kinetic constants characterizing each enzyme were derived. At all substrate concentrations, the hydrolysis rates of both clam enzymes were in the order: BTC greater than PTC greater than ATC. With oyster enzymes the ranking was ATC greater than or equal to PTC greater BTC. The specific activities of oyster heart and ganglion enzymes were similar. In contrast, clam ganglion extracts were 75-100 times more active than clam heart extracts and, with any substrate, had greater activity than either oyster enzyme. All enzyme preparations proved to be homogeneous on the bases of constant substrate activity ratios in successive column fractions, and of intermediate velocities with mixed substrates. Six cholinesterase inhibitors were tested. The specific acetylcholinesterase antagonist, B.W. 62C47, WAS MUCH MORE EFFECTIVE AGAINST OYSTER ENZYMES, WHILE THE SPECIFIC ANTIBUTYRYLCHOLINESTERASE, ISO-OMPA, almost totally inhibited calm enzyme activity, but had little effect on oyster. Eserine was the most effective inhibitor of both enzymes. In conclusion, the enzymes in oyster tissues are acetylcholinesterases, while clam enzymes are butyrylcholinesterases. Nevertheless, clam ganglion esterase is sifficiently active to hydrolyze the physiological substrate, acetylcholine. These results explain the long-observed differences in isolated heart pharmacology between ostreid and venerid bivalves.
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PMID:A comparison of the cholinesterases of an oyster (Crassostrea virginica) and a clam (Macrocallista nimbosa). 1 Mar 39

The axon plasma membrane fraction isolated from garfish olfactory nerve was analyzed for its polypeptide composition by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. There were present over 20 well-resolved polypeptide components in this membrane, and eleven of them, with an apparent molecular weight range of 22,000-130,000, accounted for most of the membrane proteins. None of the major polypeptide species present in the membrane appeared to be glycoprotein. Based on electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel, eight of the major polypeptides found in garfish nerve membrane appeared to be also present in the axon plasma membrane isolated from lobster walking leg nerve. Both garfish and lobster nerve membranes contained high concentration of lipids (66-76%) which were essentially cholesterol and phospholipids. The classes of phospholipids present were phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol and sphingomyelin. Lobster nerve membrane also contained about 3% phosphatidic acid. Assays for acetylcholinesterase in axon plasma membrane fractions isolated from different nerve sources showed a wide variation, ranging from a specific activity of 2.4 for garfish nerve to 312.5 for lobster nerve membrane.
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PMID:The polypeptide and the phospholipid components of axon plasma membranes. 13 25

The 16S and 8S forms of acetylcholinesterase (AchE), which are composed of an elongated tail structure in addition to the more globular catalytic subunits, were extracted and purified from membranes from Torpedo californica electric organs. Their subunit compositions and quaternary structures were compared with 11S lytic enzyme which is derived from collagenase or trypsin treatment of the membranes and devoid of the tail unit. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence of reducing agent, appreciable populations of monomeric through tetrameric species are observed for the 11S form. Under the same conditions, the 16S form yields only monomer and dimer in addition to a higher molecular weight species. If complete reduction is effected, only the 80,000 molecular weight monomer is dominant for both the 11S and 16S forms. Cross-linking of the 11S form by dimethyl suberimidate followed by reduction yields monomer through tetramer in descending frequency, while the 16S form again shows a high molecular weight species. A comparison of the composition of the 11S and 16S forms reveals that the latter has an increased glycine content, and 1.1 and 0.3 mol % hydroxyproline and hydroxylysine, respectively. Collagenases that have been purified to homogencity and are devoid of amidase and caseinolytic activity, but active against native collagen, will convert 16S acetylcholinesterase to the 11S form. Thus, composition and substrate behavior of the 16S enzyme are indicative of the tail unit containing a collagen-like sequence. A membrane fraction enriched in acetylcholinesterase and components of basement membrane can be separated from the major portion of the membrane protein. The 16S but not the 11S form reassociates selectively with this membrane fraction. These findings reveal distinct similarities between the tail unit of acetylcholinesterase and basement membrane components and suggest a primary association of AchE with the basement membrane.
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PMID:Molecular forms of acetylcholinesterase from Torpedo californica: their relationship to synaptic membranes. 17 42

The effect of physostigmine salicylate (0.5 mg/kg, i.p.) alone and in combination with atropine sulfate (25 mg/kg, i.p.) on levels of acetylcholine (ACh) and choline (Ch) and turnover of ACh has been studied in whole brain and striatum of mice. The animals were killed by focussed microwave irradiation and the turnover of ACh was studied after i.v. injection of deuterium labelled Ch by employing mass fragmentography. Physostigmine increased the levels of ACh in whole brain from 24.5--28.0 nmol/g(P less than 0.001) whereas there was no significant increase in striatum. The levels of Ch were also increased. The turnover rate of ACh was decreased in whole brain from 15.4 to 8.4 and in striatum from 52.9 to 24.4 nmol/g . min. Physostigmine given before or after atropine did not completely block the ACh lowering effect of atropine. When atropine was given before physostigmine the turnover rate of ACh in whole brain was increased to 24.2 nmoles/g . min. The results seem to indicate that there is no clear cut relation between the turnover rate and level of ACh in vivo. The increase of the turnover rate induced by atropine is masked unless a cholinesterase inhibitor is given to protect the newly synthesized labelled ACh released by atropine.
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PMID:Effect of physostigmine and atropine on acetylcholine turnover in mouse brain. 49 54

Detergents above their critical micellar concentration dissociate the aggregated forms of pure acetylcholinesterase from human erythrocyte membranes to a 6.5-S form, the protomer. This form is active only in presence of amphiphiles. 1. Uncharged (Triton X-100, Tweens, beta-D-octylglycoside), anionic (sodium dodecyl sulfate) and zwitterionic (lysophosphatidylcholine) detergents or bile salts (sodium cholate, deoxycholate) stabilize the 6.5-S enzyme at concentrations well below their critical micellar concentration. 2. Total erythrocyte lipids fully sustain catalytic activity of the 6.5-S form. 3. Protein-protein interactions stabilize the activity of the 6.5-S form of acetylcholinesterase. Above a critical acetylcholinesterase concentration (2.5 microgram/ml) enzyme activity no longer depends on the presence of an amphiphile as reaggregation to multiple molecular forms occurs. It is concluded that human erythrocyte membrane acetylcholinesterase is fully active only if the enzyme can undergo hydrophobic interactions with amphiphiles such as detergents, lipids or proteins.
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PMID:Effects of amphiphiles on structure and activity of human erythrocyte membrane acetylcholinesterase. 52 Mar 24

Decreases in rat plasma, erythrocyte and brain cholinesterase levels after intraperitoneal injection of 1 to 5 mg/kg of 4-benzothienyl-N-methylcarbamate (MOBAM) were compared with decrements in both spontaneous motor activity and conditioned avoidance performance produced by this compound. Significant effects were observed with all five measured phenomena at dosages producing no obvious clinical signs. In albino rats, a dosage of 2 mg/kg significantly depressed plasma and erythrocyte cholinesterase activity, and decreased motor activity 15 min after injection but only higher dosages (3 and 5 mg/kg) significantly depressed brain cholinesterase activity and avoidance performance. In Long-Evans rats, both brain cholinesterase activity and avoidance performance were significantly reduced by the lower (2 mg/kg) dosage. The avoidance impairments observed after 3 mg/kg could be prevented by prior injection with atropine sulfate. It is suggested that both central and peripheral cholinesterase changes are important in determining the nature of the behavioral effects observed after exposure to this compound.
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PMID:Behavioral and biochemical effects of the carbamate insecticide, MOBAM. 85 54

Sheep erythrocyte membranes have been shown in this laboratory to undergo spontaneous vesiculation when incubated at 4 degrees, fractionating into two bands in dextran gradients (R. McGuire and R. Barber, submitted for publication). While vesicles were observed to be formed in several solvent systems, incubation in the presence of complexors to remove divalent cations was found to be the most efficient method for both vesicle formation and their detachment from the residual membrane. We report here on the characterization of these vesicles formed by spontaneous vesiculation. In the presence of a hypotnoic buffer containing 1 mM EDTA, vesicle production proceeds linearly up to 50 hours and declines, reaching its maximum at 72 hours with up to 20% of the total membrane protein found in the upper band. This upper band is shown in electron micrographs to be composed chiefly of closed vesicles, while the particles in the lower band appear morphologically similar to the original ghosts. Total phospholipid phosphorus and cholesterol in the vesicles are enriched to the same extent, giving a lipid to protein ratio of 2 times that found for whole ghosts. The vesicles contain the same individual phospholipids as the ghosts. The protein composition of these vesicles is unique, in that they are almost depleted in the known extrinsic membrane proteins, while containing practically all types of the various glycoproteins of the original membrane. The two main intrinsic membrane proteins (with apparent molecular weights of 160,000 and 100,000) are found almost exclusively in the vesicles, virtually depleted in the residual ghost-like particles. The protein with 160,000 molecular weight is shown here to be a glycoprotein, giving an anomalous molecular weight on sodium dodecyl sulfate gels and having a molecular weight of approximately 50,000 after lipid extraction. This same glycoprotein appears to fractionate with acetylcholinesterase. From the accessibilities of the substrates to the membrane acetylcholinesterase and NADH-diaphorase, it is concluded that the vesicles are right-side-out and sealed to small molecules. There are more membrane sialic acid residues accessible to neuraminidase in the vesicles (in terms of number of residues/mg og membrane protein) than in ghosts, further supporting the conclustion that these vesicles have a normal orientation and are enriched in glycoproteins. The specific activity of acetylcholinesterase in the vesicles is increased 5- to 6-fold over that found in the original ghosts and almost 20-fold over that in the residual ghost-like particles. Consequently, spontaneous vesiculation occurs simultaneously with the enrichement of specific membrane proteins in certain regions of the lipid bilayer. It is postulated that these domains in the membrane, containing clusters of specific intrinsic membrane proteins, bud out and subsequently release glycoprotein-enriched lipid vesicles.
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PMID:Glycoprotein-enriched vesicles from sheep erythrocyte ghosts obtained by spontaneous vesiculation. 93 96

An acute case of demeton poisoning in a child is described. Intially, typical signs of organophosphate poisoning were not present, and the illness was thought to be aliphatic hydrocarbon (fuel oil) intoxication. When correct diagnosis was first suspected, treatment with pralidoxime chloride and atropine sulfate produced some perilous complications, but was probably life-saving ultimately. Plasma (pseudo) cholinesterase levels 15 to 41 hours after exposure ranged from 0.24 to 0.48 international units (IU). Approximate normal value (2.5 IU) was not reached until 5 1/2 days after exposure. Transdermal poisoning by demeton was confirmed by its presence (15.4 mg/l) in the suspected fuel oil and, at high levels, in several articles of the child's clothing. Verification of expected urinary metabolites helped confirm the diagnosis of demeton poisoning. The availability of rapid blood cholinesterase field tests in hospital laboratories, especially in agricultural areas, is pointed out as an urgent need.
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PMID:Acute demeton poisoning in a child. 97 41

1. Crossed immunoelectrophoresis was used for extensive characterization of individual proteins of human erythrocyte membranes solubilized in non-ionic detergent. 2. The precipitates were assigned to extrinsic or intrinsic proteins. 3. Four glycoproteins were identified by their lectin binding behaviour, whilst five proteins were affected by neuraminidase, indicating them to be sialoglycoproteins. 4. Enzymatic activity is retained in the solubilized system and the presence of acetylcholinesterase and an ATPase was demonstrated. The formation of phosphorylated membrane proteins on incubation with [32P]ATP was demonstrated by autoradiography on the immunoelectrophoresis plates. 5. Five proteins located on the outer cell surface were identified by antibody binding to intact cells. These same proteins were degraded by proteolytic enzymes in intact cells but only three of them were labelled by lactoperoxidase-catalysed 125I-iodination. 6. Analysis of erythrocyte membrane proteins using quantitive immunoelectrophoresis yields results concordant with those obtained by dodecyl sulfate-polyacrylamide gel electrophoresis.
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PMID:The immunochemical approach to the characterization of membrane proteins. Human erythrocyte membrane proteins analysed as a model system. 99 Mar 30


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