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

Purified tetrameric detergent-soluble acetylcholinesterase (DS-AChE) from human caudate nucleus was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence as well as in presence of a reducing agent. Staining for protein revealed a main band at 66,000 daltons (light monomer) with additional bands at 78,000 daltons (heavy monomer) as well as 130,000 and 150,000 daltons (light and heavy dimers). The same four polypeptides were also detected by Western blotting and by autoradiography of [3H]diisopropylphosphoryl enzyme. Labeling of the enzyme with 3-trifluoromethyl-3-(m-[125I]-iodophenyl)diazirine showed that the heavy monomer contained the hydrophobic anchor of the enzyme, whereas the light monomer was practically not labeled. The hydrophobic anchor was susceptible to proteolytic degradation by proteinase K. The functional molarity of DS-AChE was determined by two independent methods. Four active sites for the tetrameric enzyme were estimated. The turnover number per site was 1.7 X 10(7) mol of acetylthiocholine iodide hydrolyzed X h-1.
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PMID:Tetrameric detergent-soluble acetylcholinesterase from human caudate nucleus: subunit composition and number of active sites. 358 24

The core-specific lectin (CSL) synthesized and secreted by rat hepatocytes and the rat hepatoma H-4-II-E shows affinity for mannose and N-acetylglucosamine residues in the "core" region of asparagine-linked oligosaccharides. The CSL undergoes two stages of post-translational modification which result in an increase in its Mr from 24,000 to 26,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We have determined that the lectin undergoes hydroxylation of proline and lysine and that the hydroxylysine is glycosylated to form glucosylgalactosylhydroxylysine (GlcGalHyLys). CSL metabolically labeled with [3H]lysine and [3H]proline contains hydroxylated forms of proline and lysine. The mature form of the lectin can also be metabolically labeled with [3H]galactose. alpha,alpha'-Dipyridyl, an inhibitor of collagen prolyl and lysyl hydroxylases, prevents the metabolic incorporation of [3H]galactose and the post-translational increases in the Mr of the CSL, indicating that both events are dependent upon hydroxylation of proline and lysine. Virtually all of the hydroxylysine present in the CSL is recovered as glucosylgalactosylhydroxylysine after alkaline hydrolysis. The post-translational modifications of the CSL place it in a select family of secreted proteins which contain collagen-like sequences, including the pulmonary surfactant proteins, complement component C1q, and the 18 S asymmetric form of acetylcholinesterase.
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PMID:Identification of the post-translational modifications of the core-specific lectin. The core-specific lectin contains hydroxyproline, hydroxylysine, and glucosylgalactosylhydroxylysine residues. 361 Oct 62

Dichlorvos (dimethyl 2,2-dichlorovinyl phosphate) was administered orally to German Shorthair Pointer dogs at approximately 60 mg/kg (twice the usual clinical dose). Plasma and erythrocyte cholinesterase (ChE) was monitored prior to, 90 min, and 180 min post-ingestion. 2-PAM (20 mg/kg IV) and atropine sulfate (0.022 mg/kg IM) were administered 90 min after the dichlorvos to paired treated and control dogs. The telemetered electrocardiographic (ECG) signal was analyzed by a Vagal Tone Monitor (VTM) to yield mean heart period (msec) and an estimate of the amplitude of respiratory sinus arrhythmia (V in natural log values of msec2) for five min intervals. Dichlorvos did not cause cholinomimetic symptoms even though blood cholinesterase was significantly inhibited (plasma -51.3% and erythrocyte -43.7%). The atropine sulfate treatment resulted in the expected vagolytic effects in both the control and the dichlorvos treated dogs, but the atropine effects were attenuated in the latter dogs. Three weeks later, ChE activity was not significantly depressed in the dichlorvos treated dogs, and their V responses to atropine were more similar to the responses in control dogs.
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PMID:Latent dichlorvos neurotoxicity detected by vagal tone monitoring in dogs. 362 83

The membrane-bound acetylcholinesterase (AchE) from human peripheral blood lymphocyte gives only one symmetrical peak on sucrose density gradient centrifugation in the presence of Triton X-100 detergent, with the calculated sedimentation coefficient of 6.5 S. However, this dimeric form of AchE was converted to a monomeric 3.8 S form when treated with 2-mercaptoethanol and iodoacetic acid. The results are consistent with studies which have shown by sodium dodecyl sulfate gel electrophoresis that the enzyme is built up of two identical monomers inter-linked by disulfide bond(s). Under reducing conditions, revealed a single species of 70,000 molecular weight, whereas under non-reducing conditions, another species of 140,000 molecular weight of the AchE was found. Polyacrylamide gel electrophoresis indicated a single band with AchE activity in the presence of Triton X-100. In contrast, in the absence of the same detergent multiple band pattern could be observed. These results suggest that membrane-bound AchE enzyme is present in homogenous dimeric form on human lymphocyte membrane.
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PMID:Molecular form of human lymphocyte membrane-bound acetylcholinesterase. 365 87

Visual evoked responses (VER) to counterphased gratings were recorded from area 17 of cat visual cortex prior to and following administration of diisopropylfluorophosphate (DFP). The VER and acetylcholinesterase (AChE) activity of blood, retina, and visual cortex were reduced significantly following DFP administration. Approximately two hours after exposure to 4 mg/kg DFP, the VER began to recover and in some cats returned to base line levels. In contrast, blood, retina, and cortex AChE activity showed little, if any, tendency for recovery throughout the experiment. Since atropine sulfate provided at least partial recovery of the VER following DFP without affecting AChE inhibition, an accumulation of acetylcholine (ACh) probably is involved in the initial visual loss. However, recovery of the VER over time while AChE remained severely inhibited implicates mechanisms other than, or in addition to, accumulation of ACh at receptor sites.
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PMID:Recovery of the visual evoked response in the cat following administration of diisopropylfluorophosphate, an irreversible cholinesterase inhibitor. 369

Seizure produced by intrahippocampal injection of zinc sulfate in rabbits is a new chronic model of experimental epilepsy. In this model, the clinical manifestations are easily observed and are expressed not only as partial clonic seizures, but also by secondary generalized seizures. The electrohippocampalogram (EHG) and electrocorticogram (ECoG) discharges change correspondingly during both types of seizures, and last for weeks. The mechanism for induced seizures may be partly related to the inhibitory effect of zinc sulfate injections on the acetylcholinesterase (AchE) activity in the hippocampus. The commonly used antiepileptic drugs, such as phenobarbital and phenytoin, afforded protection against the zinc-induced secondary generalized clonic seizures and alleviated the partial clonic seizures but had no influence on the EHG- and ECoG-monitored periodic bursts of spike discharges. Nitrazepam was found to antagonize both types of seizures and also transiently restored the EHG and ECoG to normal. D-penicillamine, a metal chelator, may be the most effective agent for the treatment of zinc-induced seizures; the agent, in addition to affording protection against both types of seizures, also caused the periodic burst spike discharges in EHG and ECoG to disappear.
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PMID:Features of seizures and behavioral changes induced by intrahippocampal injection of zinc sulfate in the rabbit: a new experimental model of epilepsy. 369 33

Single-pass perfusion of mouse livers in situ with the phosphorothioate pesticide parathion resulted in formation of the cholinesterase inhibitor paraoxon (PO), p-nitrophenol (PNP), p-nitrophenyl sulfate (PNPS), and p-nitrophenyl glucuronide (PNPG). Daily pretreatment of mice with phenobarbital (80 mg/kg, ip) for 4 days induced hepatic cytochrome P-450 content, as well as oxidative activation and oxidative detoxification of parathion, as measured in vitro. However, phenobarbital pretreatment did not alter production of PO from parathion in mouse livers perfused in situ, although it increased production of PNP, PNPS, and PNPG. Additionally, phenobarbital pretreatment antagonized the acute toxicity of parathion in mice. These results indicate that phenobarbital pretreatment clearly induces that form(s) of cytochrome P-450 catalyzing conversion of parathion to PO. Yet increased amounts of PO do not exit perfused livers from phenobarbital pretreated mice. Instead, the enhanced detoxification of parathion to PNP, PNPS, and PNPG likely results in the observed antagonism of parathion's acute toxicity.
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PMID:The effects of phenobarbital pretreatment on the metabolism and acute toxicity of the pesticide parathion in the mouse. 376 30

The generally accepted explanation for the effects of oximes in countering organophosphorus (OP) anticholinesterase is reactivation of the inhibited acetylcholinesterase (AChE). With soman, the inhibited AChE rapidly becomes resistant to oxime reactivation due to a phenomenon called aging. Thus, pretreatment with pyridostigmine (Py) or physostigmine (Ph) followed by atropine sulfate therapy is required to achieve significant protection against soman; the effectiveness of a pretreatment/therapy (P/T) regimen can be further increased against certain OPs (e.g. sarin and VX) by including an oxime in the therapy regimen. The P/T regimen is clouded by a controversy concerning the use of oximes in the treatment of carbamate intoxication, because 2-PAM has been reported to exacerbate intoxication by some carbamates and to have no effect on decarbamylation rates. To better understand the role of oxime therapy in the theory of pretreatment of OP intoxication we examined the effects of 2-PAM and HI-6 on the rate of decarbamylation of Py-inhibited erythrocyte AChE in vitro and in vivo, and studied the effects of atropine plus 2-PAM or HI-6 on Py toxicity. In decarbamylation experiments, Py-inhibited guinea pig erythrocytes were washed free of excess Py and incubated with vehicle or oxime (2 X 10(-4) M, pH 7.3 and 37 degrees C). Aliquots were assayed for AChE activity at various times during a 60 min incubation period. Rate constants were calculated and compared to determine whether the presence of oxime affected decarbamylation. The data from in vitro and in vivo experiments revealed that oximes accelerated the decarbamylation (p less than 0.05) of inhibited AChE. Lethality data for Py-treated guinea pigs showed that treatment with atropine (23 mumoles/kg, im) plus 2-PAM or HI-6 (145 mumoles/kg, im) at one min after injection of Py increased the protective ratio from 4.2 (atropine only) to 5.1 and 12.2, respectively. It is suggested that the enhanced therapeutic efficacy of atropine by oximes against Py intoxication is related to oxime-induced reactivation.
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PMID:Oxime-induced decarbamylation and atropine/oxime therapy of guinea pigs intoxicated with pyridostigmine. 380 51

A previous report (Watkins, M.S., Hitt, A.S. and Bulger, J.E. (1977) Biochem. Biophys. Res. Commun. 79, 640-647) has indicated that the asymmetric forms of Electrophorus acetylcholinesterase bind exclusively to sphingomyelin vesicles through interaction with the collagen-like 'tail' portion of the enzyme. We report here that acetylcholinesterase also binds to phosphatidylcholine vesicles containing saturated fatty acyl chains and to egg phosphatidylcholine vesicles containing cholesterol. This suggests preferential binding of acetylcholinesterase to membranes of lower fluidity. Surface charge of vesicles and density of zwitterionic lipid headgroups do not significantly affect binding of native acetylcholinesterase. The presence of chondroitin sulfate or hyaluronic acid slightly increases the binding of native acetylcholinesterase to sphingomyelin vesicles, while the presence of 1 M NaCl, bovine serum albumin, or tissue fractions enriched in basement membrane diminish binding. The dissociation constant for native acetylcholinesterase and sphingomyelin vesicles is (1.0-1.5) X 10(-7) M, as measured by a flotation binding assay. The globular, 11S form of acetylcholinesterase also binds to lipid vesicles, although not to the same degree as native acetylcholinesterase. This suggests that the collagen tail of the enzyme enhances binding, but is not essential for binding to occur. These results are consistent with the location of acetylcholinesterase on the surface of the postsynaptic plasma membrane in vivo.
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PMID:Effect of membrane fluidity upon binding of Electrophorus acetylcholinesterase to lipid vesicles. 391 84

The possible role of nerve activity in triggering changes in the localization of acetylcholine receptors (AChRs) and cholinesterase (ChE) on nerve-contacted Xenopus muscle cells has been assessed. The localization of these molecules was examined on nerve-contacted and noncontacted muscle cells in cultures of spinal cord and myotomal muscle derived from Xenopus embryos. Sites of high AChR density were revealed by staining with fluorescent alpha-bungarotoxin and sites of ChE localization were revealed histochemically. Localization of AChRs and ChE at sites of nerve-muscle contact occurred when the culture medium contained 1.2 micron tetrodotoxin (TTX), 1.2 micron TTX, 10 mM magnesium, and no calcium salts, 1.2 micron TTX and 2 mM manganese, or 106 mM potassium methyl sulfate instead of sodium chloride. The nerve-contacted muscle cells in each of these modified culture media also exhibited a reduced incidence of AChR and ChE patches away from the site of contact. It is concluded that the neural factor(s) that triggers the local and remote changes in AChR and ChE distribution can be supplied to the neurites and externalized in the absence of nerve impulses, and that the nerve and muscle cells can interact even when they are largely depolarized.
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PMID:Localization of acetylcholine receptors and cholinesterase on nerve-contacted and noncontacted muscle cells grown in the presence of agents that block action potentials. 395 89


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