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)

Studies have been made on substrate specificity of acetylcholinesterase (AChE;EC 3-1-1-7) from the electric organ of the ray T. marmorata with respect of choline and thiocholine esters, as well as on the effect of pH, salts and organophosphorus inhibitors (OPI) on the activity of the enzyme. Acetylcholine (ACh), propionycholine (PrCh) acetyl-beta-methylcholine (MeCh), acetylthiocholine ((ATCh) and propionylthiocholine (PrTCh) were hydrolyzed by the enzyme studied at the following relative rates-100: 28.8: 18.3: 87.2: 18.9 correspondingly. In all the cases, inhibition of the enzyme by high concentrations of the substrate was observed. As compared to other AChE, the enzyme from T. marmorata exhibits the highest affinity to ACh. For all the substrates studied, pH dependence of AChE activity followed the curve with maximum 7.5 for ACh and PrCh, 8.0-8.5 for ATCh and MeCh and 7.5-8.5 for PrTCh. Various salts (MgCl2), KCl, NaCl, NaBr, KI) increased AChE activity, the increase being the highest with MgCl2 (3.3 times) and NaCl (2.5X). Biomolecular rate constants ((k) II) for the interaction of AChE investigated with OPI containing cationic group-methylsulfomethylates, O-ethyl-S-(beta-ethylmercapto) ethylmethylthiophosphonate and O,O-diethyl-S-(beta-ethylmercapto) ethylthiophosphate, as well as methyl iodide O,O-disopropyl-S-(beta-phenylmethylamino) ethylphosphate-were significantly higher as compared with k(II) values for corresponding compounds without the cation. The value of k(II) sharply decreased with the increase in the size of the acyl radicals at phosphorus atom in the molecule of OPI.
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PMID:[Acetylcholinesterase from the electric organ of the ray Torpedo marmorata]. 0 75

The response of various species of Anser and Branta geese and other avian species to the ingestion of carbophenothion (S-[[(4-chlorophenyl)thio]methyl] O,O-diethyl phosphorodithioate) has been investigated. Optimum assay conditions for measurement of glutamate oxaloacetate transaminase, glutamate dehydrogenase, sorbitol dehydrogenase, and cholinesterase in avian plasma were developed for the study. The administration of acutely toxic doses of carbophenothion to Japanese quail, pigeons, and chickens, and to Greylag, Pink-footed, Greenland White-fronted, and Canada geese led to species-dependent responses for both plasma glutamate oxaloacetate transaminase and cholinesterase levels. Carbophenothion administered to Japanese quail at several dose levels produced changes in plasma enzyme levels which were dependent on dose and time. The level of plasma glutamate oxaloacetate transaminase after dosing in the Anser family of geese rose more rapidly than in the Branta species but no change was found in this enzyme in either chickens or pigeons. In contrast to geese and pigeons, chickens exhibited no plasma cholinesterase inhibition for 3 hr after dosing. These enzyme changes demonstrate a species variation in the toxicological response of birds to a pesticide and indicate the desirability of using more than one avian species for pesticide toxicity testing.
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PMID:Variation in the response of plasma enzyme activities in avian species dosed with carbophenothion. 72 17

A new series of cyclic organophosphorus esters, 2-S-[2'-N,N-dialkylamino)ethyl]thio-1,3,2-dioxaphosphorinane 2-oxide and their quaternary derivatives, was synthesized and studied as potential antiglaucoma agents. Thes compounds inhibit acetylcholinesterase (E.C.3.1.1.7)at a bimoecular rate constant (ki) in the range of 10(3)-10(4) M-1 min-1. Values of the affinity (K) and phosphorylation (k') rate constants for this enzyme indicate that k' is responsible for the relatively low values of ki as compared with similar data for the open-chain analogues, O,O-diethyl phosphorothiolates (10(6) M-1 min-1). The mammalian toxicity of the new compounds in terms of acute LD50 values in mice is 1-3 x 10(3) less than that of phospholine, an open-chain analogue. In an initial clinical trial, one member of the new series (alkyl = C2H5) caused a significant decrease of intraocular pressure in aphakic glaucoma, while phospholine proved to be ineffective.
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PMID:Synthesis and properties of 2-S-(N,N-dialkylamino)ethyl)thio-1,3,2-dioxaphosphorinane 2-oxide and of the corresponding quaternary derivatives as potential nontoxic antiglaucoma agents. 95 Jun 51

O-Nitrophenyl dimethylcarbamate and organophosphorus inhibitors O-n-propyl-p-nitrophenyl methylphosphonate, O-n-butyl-p-nitrophenyl methylphosphonate, O,O-diethyl-p-nitrophenyl phosphate, O-n-butyl-S-(beta-ethylmercaptoethyl) methylthiophosphonate, methysulphate of O,O-diethyl-S-(beta-phenyldimethylammoniumethly) thiophosphate were used in the titration of acetylcholinesterase active site concentratration in Naja naja oxiana venom. No side reactions with the acetylcholinesterase molecule as well as with other components of the venom were observed. In titration the effective concentrations of organophosphorus inhibitors with asymmetric phosphorus were 50% of their analytical concentrations, since cobra venom cholinesterase showed practically absolute stereoselectivity against the compounds.
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PMID:[Acetylcholinesterase of cobra venom. Determination of concentration of active sites]. 103 Jun 38

Catalytic properties of human blood erythrocyte acetylcholinesterase and horse blood serum butyrylcholinesterase immobilized and nonimmobilized in the gelatin membrane have been comparatively studied. Cholinesterase immobilization induces an increase in the Michaelis constant value and a decrease in the maximum rate value in reactions of enzymic hydrolysis of thiocholine ethers, but exerts no effect on these kinetic parameters in case of enzymic hydrolysis of indophenylacetate. The effect of reversible inhibitors: galanthamine, N-methyl-4-piperidinyl benzylate and 1,2,3,4-tetrahydro-9-aminoacridine (tacrine), as well as of irreversible inhibitors: O-ethyl-O-(4-nitrophenyl)ethyl phosphonate (armin), diisopropyl fluorophosphate (DFP), O,O-diethyl-O-(4-nitrophenyl) phosphate (paraoxon) and O,O-dimethyl-O-(2,2-dichlorovinyl) phosphate (DDVP) on immobilized cholinesterases is weaker as compared with the effect on nonimmobilized enzymes. The results obtained are discussed for the effect of immobilization on the catalytically active enzyme surface.
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PMID:[Catalytic properties of cholinesterases immobilized in a gelatin membrane]. 208 92

A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.
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PMID:[Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid]. 209 24

Some characteristics of the hydrolysis of O,O-dimethyl-2,2 dichlorovinyl phosphate (DDVP) by human serum are reported and compared with the hydrolysis of O,O-diethyl-4-nitrophenyl phosphate (paraoxon) which is a substrate for Paraoxonase, a known "A"-esterase of human serum. When incubated with human serum, DDVP was losing its inhibitory power toward acetylcholinesterase (AChE). The loss of DDVP followed first order kinetics and was proportional to serum dilution. The disappearance of DDVP after incubation with human serum was not due to protein binding. Apparent Km and Vm for the hydrolysis of DDVP were 7.1 mM and 143 nmol.min-1.ml-1. The pH sensitivity, EDTA inhibitory and Ca2+ requirements of DDVP-ase were similar to those of Paraoxonase. DDVP inhibited the Paraoxonase activity and paraoxon inhibited the DDVP-ase activity. Ca2+, Ag+ and Hg2+ were better inhibitors of the Paraoxonase than the DDVP-ase. The rate of heat inactivation was also different; at 55 degrees Paraoxonase inactivated almost completely within 10 min, while DDVP-ase lost only about 10% activity over 1 hr. Consequently, DDVP-ase and Paraoxonase can be differentiated by means of heat sensitivity. The DDVP-ase was normally distributed in a population of 60 individuals, while Paraoxonase is known to show a marked polymorphism.
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PMID:Human serum "A"-esterases. Hydrolysis of O,O-dimethyl-2,2-dichlorovinyl phosphate. 253 85

Memory impairment is one of the recurrent complaints of agricultural workers repeatedly exposed to organophosphorus insecticides. In an effort to establish an animal model for such behavioral effects, which would allow studying its underlying biochemical mechanism(s), in this study we evaluated spatial memory in animals following repeated organophosphate exposure. Male Long-Evans rats were given daily i.p. injections of either diisopropylfluorophosphate (DFP; 1 mg/kg/day) or disulfoton (O,O-diethyl S-[2-(ethylthio)ethyl] phosphorodithioate; 2 mg/kg/day) for 14 days. Acetylcholinesterase activity was inhibited 71-77% in the cortex, hippocampus, and striatum of rats treated with DFP, and 73-74% in those treated with disulfoton. Binding of [3H]quinuclidinyl benzilate ([3H]QNB) to cholinergic muscarinic receptors in the same brain areas was reduced 16-28% in organophosphate-treated rats. This decrease was due to a reduction in muscarinic receptor density (Bmax) with no changes in receptor affinity. At the end of the treatment rats were tested for spatial memory using the spontaneous alternation task in a T-maze. Rates of true spontaneous alternation were 64.4, 45.0, and 44.8% in animals which received corn oil, DFP, or disulfoton, respectively (P less than 0.05). These results indicate that prolonged inhibition of acetylcholinesterase caused by repeated organophosphate exposure alters spatial memory functions in rats, as well as causing a loss of muscarinic receptors. Considering the role of the cholinergic system in cognitive processes, these biochemical alterations could be related to the observed behavioral changes and may offer a potential explanation of the memory impairment reported by workers chronically exposed to organophosphates.
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PMID:Spatial memory impairment and central muscarinic receptor loss following prolonged treatment with organophosphates. 334 Oct 49

Tri-o-cresyl phosphate (TOCP) is a neurotoxic organophosphorus compound that induces a characteristic central-peripheral distal axonopathy and Wallerian-type degeneration, 6-14 days after exposure. This organophosphorus compound-induced delayed neurotoxicity (OPIDN) has been extensively studied in the chicken, the standard test model. Reports of neurotoxic agents causing adverse effects on the male reproductive system initiated the present study which was designed to examine the effects of TOCP on the rooster. Previous work from this laboratory has demonstrated 100 mg TOCP/kg/day to be an OPIDN-inducing dose with minimal mortality in roosters. This dose level was administered to adult leghorn roosters (p.o., n = 10) for 18 consecutive days. By days 7-10 of the study, TOCP-treated birds exhibited limb paralysis characteristic of OPIDN. Analysis at termination revealed significant inhibition of neurotoxic esterase activity (NTE) in both brain and testis. There was also a slight decrease in brain acetylcholinesterase (AChe) activity. Sperm motility was shown to be greatly decreased. In addition, sections of formalin-fixed, methacrylate-embedded testes from TOCP-treated birds showed vacuolation of, and disorganization in the seminiferous epithelium. The marginal body weight decreases (17%) in treated animals were not considered to contribute to the testicular toxicity induced by TOCP. Parathion (O,O-diethyl-O-4-nitrophenyl phosphorothioate, 0.1 mg/kg/day, p.o., n = 3) was used as a positive control for AChE inhibition and a negative control for inducing OPIDN. Roosters treated continuously with parathion showed a decrease in brain AChE activity, but no changes in NTE, testicular histology, or limb function. These studies demonstrate the testicular toxicity of TOCP in roosters and suggest that this effect is not related to the chemical's anticholinergic action.
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PMID:Testicular toxicity following oral administration of tri-o-cresyl phosphate (TOCP) in roosters. 361 3

The changes in brain acetylcholinesterase (AChE), acid phosphatase (APase), and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP), and plasma butyrylcholinesterase (BuChE) activities were investigated in hens treated with a single, dermal dose (100-1000 mg/kg) of S,S,S-tri-n-butyl phosphorotrithioate (DEF). Three control groups consisted of hens left untreated, given a single, dermal dose of 500 mg/kg tri-o-cresyl phosphate (TOCP, positive control for organophophorous compound-induced delayed neurotoxicity), or 10 mg/kg O,O-diethyl O-4-nitrophenyl phosphorothioate (parathion, negative control). Brain AChE activity, determined 28 days after application, was significantly inhibited in hens given 500-1,000 mg/kg DEF and in TOCP- and parathion-treated hens. In contrast, brain APase and CNP activities were significantly higher in all treatments as compared with those of the untreated hens. Parathion, however, caused the least increase in these enzymatic activities as compared to DEF or TOCP. A single, dermal dose of DEF or TOCP also caused an initial decrease in plasma BuChE activity with maximum depression of enzymatic activity observed 1 to 7 days after administration. This decrease was dose dependent and the enzymatic activity showed partial recovery with time. Hens treated with single, dermal doses of DEF, ranging from 250 to 1000 mg/kg, developed ataxia which progressed to paralysis in some hens. Histopathologic examination revealed axon and myelin degeneration of the spinal cord and peripheral nerves of some hens. The severity and frequency of the neuropathologic lesions were dose dependent. Neurologic dysfunctions and neuropathologic lesions seen in DEF-treated hens were similar to those exhibited in TOCP-treated hens. While parathion produced acute cholinergic effects, it did not cause delayed neurotoxicity. The changes in brain and plasma enzymes are discussed in relation to their role in the pathogenesis of DEF-induced delayed neurotoxicity.
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PMID:Brain acetylcholinesterase, acid phosphatase, and 2',3'-cyclic nucleotide-3'-phosphohydrolase and plasma butyrylcholinesterase activities in hens treated with a single dermal neurotoxic dose of S,S,S-tri-n-butyl phosphorotrithioate. 395 29


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