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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pretreatment of rats with 10 mg of ethylestrenol (17alpha-ethylestr-4-en-17beta-ol) by force feeding twice daily for three days and once on the fourth day decreased the severity of parathion (0,0-diethyl 0-4-nitrophenyl phosphorothioate) toxicity and caused a 150% increase in the parathion LD50 in male animals. It decreased by 51% cholinesterase inhibition in the brain caused by i.p. injection of 2 mg of parathion/kg body weight but not that of an equitoxic dose (0.5 mg/kg) of its active metabolite, paraoxon (0,0-diethyl 0-4-nitrophenyl phosphate). It decreased by 29% cholinesterase inhibition in plasma following i.p. administration of parathion but caused only a 16% decrease in cholinesterase inhibition following administration of the equitoxic dose of paraoxon. It did not protect against brain cholinesterase inhibition by 4 mg/kg of parathion given i.v.; however, brain parathion levels were 16% lower in rats pretreated with ethylestrenol than in control rats. It increased the rate of inactivation of both parathion and paraoxon by liver microsomal enzyme preparations. Thus enzyme induction seems to account for the protection afforded by ethylestrenol to toxicity following poisoning by organophosphates.
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PMID:The protective effects of ethylestrenol against acute poisoning by organophosphorus cholinesterase inhibitors in rats. 63 20

Aminoalkyl benzenesulfonyl fluorides, like organophosphates, act as irreversible inhibitors of serine proteinases by splitting off hydrogen fluoride to form an enzyme-inhibitor complex, stable in the physiological pH region. Several of these compounds are characterized by a higher rate of inhibition when trypsin is used and the second order rate constants are compared with those of organophosphates. On the other hand, upon inhibition of human serum cholinesterase by DFP and 4-nitrophenyl diethyl phosphate, some orders of magnitude higher than that of benzenesul fonyl fluorydes are observed. As shown by an oral toxicity study in mice similar differences exist with respect to LD50 values.
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PMID:[Inhibition of the activity of human serum cholinesterase by aminoalkyl benzenesulfonyl fluorides]. 102 6

A series of quaternary salt derivatives of 2-[(hydroxyimino)methyl]-1-methylimidazole incorporating various side chains bearing ether, silyl, nitrile, ester, halogen, nitro, sulfone, amino, or aminosulfonyl substituents was prepared and evaluated in vivo for the treatment of anticholinesterase intoxication. Test results in the mouse revealed that the type and location of the side-chain substituent both have a significant influence on the toxicity and antidotal effectiveness of the compounds. Some of the more active examples represent the most potent therapeutics to date against intoxication by the powerful cholinesterase inhibitors soman and tabun. Significantly, the antidotal effectiveness of the compounds was not dependent on the inhibiting agent nor was there any correlation between in vivo efficacy and in vitro reactivation of ethyl (4-nitrophenyl)methylphosphonate inhibited human acetylcholinesterase. These observation suggested that the main mode of antidotal protection by the compounds is something other than enzyme reactivation.
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PMID:Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 4. Effect of various side-chain substituents on therapeutic activity against anticholinesterase intoxication. 201 11

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

Hydrolytic "A"-esterase activities of various tissues of rat (plasma, liver, kidney, brain and intestinal mucosa) against selected OP esters of diverse structure as potential substrates (paraoxon, di-n-propyl paraoxon, di-n-butyl paraoxon, chlorpyrifos oxon, di-(4-phenyl butyl) phosphorofluoridate and the chiral isomers of ethyl 4-nitrophenyl phenylphosphonate) were studied. We have developed a sensitive and widely applicable assay depending on measuring decline in residual inhibitory power of any chosen OP against horse serum cholinesterase: for seven compounds examined so far I50s against BuChE ranged from 0.07 to 70 nM, and it is easy to monitor loss of OP starting from an initial 25 microM concentration. Progressive destruction rates were always highest in liver and plasma with activity sometimes detectable in kidney, brain but not in intestinal mucosa, but the ratios of activity between tissues differed for different substrates. At 25 microM/37 degrees/pH 7.2 hydrolysis rates ranged from 8500 nmol/min/g liver for di-(4-phenylbutyl) phosphorofluoridate down to 0.8 nmol/min for the butyl analogue of paraoxon; the rate for L(-) isomer of EPN oxon (23 nmol/min/g liver) was greater than 2x that for the D(+) isomer and for paraoxon. From our data we conclude that several OP hydrolases exist whose identity may be further characterised by use of selective substrates.
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PMID:Degradation by rat tissues in vitro of organophosphorus esters which inhibit cholinesterase. 271 24

1. Hydrolysis of the drug esters procaine, chloramphenicol succinate, and prednisolone succinate was studied. Addition of soman to guinea pig liver microsomes caused a dose-dependent inhibition of hydrolysis of all three substrates; at the highest soman concentration (1 microM), ester hydrolysis was totally abolished. 2. Ester hydrolysis was also measured in liver microsomes from guinea pigs pretreated with soman at a low dose (10% of LD50) or at a high dose (90% of LD50) either 1 h or 12 h before killing. Plasma-cholinesterase activity was decreased in all pretreated animals. Liver carboxylesterase activity, measured with the three drug substrates and by hydrolysis of 4-nitrophenyl acetate was increased by all pretreatments. 3. This enhancing effect varies with the substrate and increases with dose of soman. The 12 h pretreatment produced a greater increase in activity than did the 1 h pretreatment. 4. These studies indicate that soman is a potent inhibitor of carboxylesterase activity in vitro but increases the activity of the liver enzyme when administered in vivo.
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PMID:Alteration of hepatic carboxylesterase activity by soman: inhibition in vitro and enhancement in vivo. 275 15

Sialate 9(4)-O-acetylesterases (EC 3.1.1.53) have been isolated from equine liver, bovine brain and influenza C virus. In this latter case, the esterase represents the receptor-destroying enzyme of the virus. The kinetic properties of these enzymes were determined with Neu5,9Ac2 and in part with 4-methylumbelliferyl acetate and Neu5,9Ac2-lactose. The Km values vary between 0.13 and 24 mM and the Vmax values from 0.55 to 11 U/mg of protein. The pH optima are in the range of 7.4-8.5, the molecular masses at 56,500 and 88,000 Da. In addition to a fast hydrolysis found for aromatic acetates, such as 4-methylumbelliferyl acetate or 4-nitrophenyl acetate, N-acetyl-9-O-acetylneuraminic acid is de-O-acetylated at the highest relative rate. Other substituents at the 9-position, such as lactoyl residues, or acetyl groups at other positions within the side chain are not hydrolyzed. Neu4,5Ac2, however, is a substrate for all 3 enzymes. The hydrolysis rates of this ester function, which renders sialic acids resistant to the action of sialidases, vary from 3 to 100% relative to Neu5,9Ac2. Whereas Neu5,9Ac2-lactose is hydrolyzed by the bovine and viral esterases, other O-acetylated sialic acids in glycoconjugates are only attacked by the enzyme from influenza C virus and not by that from bovine brain. The esterase from horse liver also releases 4-O-acetyl groups from equine submandibular gland mucin. By incubation with appropriate substrates and inhibition studies, carboxylesterase, amidase and choline esterase activities were excluded, as well as the cleavage of other acyls, e.g., butyryl groups. Thus, the enzymes investigated belong to the acetylesterases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sialate O-acetylesterases: key enzymes in sialic acid catabolism. 314 20

The carboxylesterase activity in both plasma and liver of guinea-pig were separated into three main peaks by chromatofocusing. Two of the three plasma enzymes were retained by affinity chromatography on Affi-Gel Blue (100-200 mesh). Isoelectric points determined by chromatofocusing or isoelectrofocusing were pI 6.1, pI 5.2 and pI 4.0 for the plasma enzymes, and pI 5.7, pI 5.2 and pI 4.5 for the liver enzymes. The effect of selective esterase inhibitors, soman, physostigmine (cholinesterase inhibitor) and bis-4-nitrophenyl phosphate (carboxylesterase inhibitor), suggested that the three enzymes in both tissues may be regarded as carboxylesterases. However, the pI 5.7 carboxylesterase was partially inhibited by physostigmine, and the pI 4.5 carboxylesterase was almost not affected by bis-4-nitrophenyl phosphate. The ratio between the activities towards 4-nitrophenyl butyrate and methyl butyrate differed among the carboxylesterases in both tissues. All three carboxylesterases in plasma were partially reactivated by diacetylmonoxime after soman inhibition in vitro, but to a different extent. The soman inhibited liver carboxylesterases were not reactivated by diacetylmonoxime.
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PMID:Carboxylesterases in guinea-pig plasma and liver. Tissue specific reactivation by diacetylmonoxime after soman inhibition in vitro. 368 30

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

This report documents studies on the spontaneous reactivation of human erythrocyte acetylcholinesterase and human serum butyrylcholinesterase following inhibition by organophosphinate esters. The spontaneous reactivation reactions were carried out at 26.0 degrees C in 0.10 M phosphate buffer of pH 7.6. Based upon results at 24 h, human serum butyrylcholinesterase inhibited with 4-nitrophenyl methyl (4-methoxyphenyl) phosphinate was the most responsive (92.5% recovery) of the nine esters studied. Using the same criteria, the most active compound in the human erythrocyte acetylcholinesterase studies was 4-nitrophenyl methyl(phenyl)phosphinate (74.2% recovery). With seven of the nine compounds examined the response was greater from the serum enzyme than from the erythrocyte enzyme.
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PMID:Spontaneous reactivation of phosphinylated human erythrocyte acetylcholinesterase and human serum butyrylcholinesterase. 398 30


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