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)

A simple and reliable method based on cholinesterase inhibition is proposed to detect organophosphate pesticides in water. The potentiometric method to measure enzymatic activity was applied to an immobilized cholinesterase film coupled directly to a flat glass pH electrode. Under controlled laboratory conditions, it was possible to correlate inhibition of cholinesterase activity with intramembranal pH shifts induced by substrate hydrolysis. Measurements can be performed with such an enzyme electrode system in real time by monitoring the inhibition process, or after incubation of the enzymatic film. Technical grade compounds of methylparathion, azinphosethyl , and mevinphos were used as examples, and detected from ppm to several ppb after oxidative treatment. The sensitivity of the enzyme sensor depends on the inhibitory power of the pesticide molecules, and therefore determines additional toxicity information unavailable from other physico-chemical methods. This type of sensor could be used for screening purposes in the detection of pesticides in water pollution control and is intended to be complementary to existing analytical methods.
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PMID:Detection of organophosphorous pesticides with an immobilized cholinesterase electrode. 673 98

Temperature and water uptake were reduced to a greater degree in ovariectomized female and normal male rats than in sham-operated female rats following an acute administration of 1 mg/kg of the anticholinesterase diisopropyl fluorophosphate (DFP). Ovariectomy also led to a significant reduction in the level of serum cholinesterase activity. These findings add further support for the hypothesis that the sex-dependent effects of DFP are due, at least in part, to sex differences in serum cholinesterase activity.
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PMID:The influence of ovariectomy on the sex-dependent effects of the anticholinesterase diisopropyl fluorophosphate. 679 89

The quantitative structure--activity relationship of double alkyl chain drugs, including alkanols, aliphatic esters, ketones, barbiturates, amphetamines, butyrylcholinesterase inhibitors, antimalarials, and rifamycin amides, is investigated. A series of double-chain homologues, CnH2n+1XCmH2m+1, in which n changes, keeping m constant, is classified into three types: in type IIL, n greater than m; in type IIE, n = m; in type IIS, n less than m. When a linear relationship, vis., log (1/C) = an + b, holds, the slope a depends on the type; aI greater than or equal to aIIL greater than aIIE greater than aIIS. Here aI means the slope for single-chain homologues. The same order is observed for the equation, log hydrophobicity = an + b, where the hydrophobicity of drug denotes the water solubility, the critical micelle concentration, and the partition coefficient for the 1-octanol--water phases. Therefore, decreased biological activity of a double-chain drug relative to that of a single-chain isomer can be explained by a decreased hydrophobicity of the double-chain drug, due to the intramolecular association of these chains in water. When a parabolic relationship between log (1/C) and n holds, the optimum n depends on the type: nopI less than nopIIL less than nopIIE. This order is also explicable on the basis of a decreased hydrophobicity of double-chain drug. The N-dealklation rate of amphetamines in vivo appears to be affected by the steric factor as well as the hydrophobic factor. A decreased hydrophobicity of double-chain compounds should be taken into consideration for estimating their partition coefficients.
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PMID:Quantitative structure--activity relationship of double alkyl chain drugs. 684 9

A direct and continuous kinetic method for the fluorimetric assay of various hydrolases by using new, highly water-soluble substrates is described. The latter consist of esters of strongly fluorescent 1-hydroxypyren-3,6,8-trisulfonic acid trisodium salt with acetic, butyric, caprylic, and oleic acid. Km and vmax values are given for the hydrolytic activity of porcine liver carboxylic ester hydrolase, wheat germ lipase, candida cylindracea lipase, hog kidney acylase I, and bovine pancreas alpha-chymotrypsin, while others (acetylesterase, trypsin, and cholinesterase) were studied qualitatively. By proper choice of the substrate, a fair selectivity may be achieved. Detection limits as low as 1 microgram enzyme/ml are found in some cases. Advantages of these new substrates over existing ones are briefly discussed.
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PMID:Fluorimetric assay of hydrolases at longwave excitation and emission wavelengths with new substrates possessing unique water solubility. 684 35

Affinity electrophoresis has been applied to the study of the multiple molecular forms of three human plasma cholinesterase phenotypes (usual enzyme U, atypical enzyme A and intermediate UA). Electrophoreses were carried out in polyacrylamide gels containing a water-soluble macromolecular derivative of m-amino-(substituted)-phenyltrimethylammonium immobilized within the gel network. Apparent dissociation constants (KD app) were estimated from the mobilities of the enzymes versus ligand concentration. The ratio of KD app values of the molecular forms of phenotypes A and U which is approximately 2 is consistent with the hypothesis that the anionic site is altered in atypical enzyme.
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PMID:[Possibilities of study of the human plasma cholinesterase variants by affinity electrophoresis]. 686 45

Extracts of the nematode Caenorhabditis elegans contain five molecular forms of acetylcholinesterase (AChE) activity that can be separated by a combination of selective solubilization, velocity sedimentation, and ion-exchange chromatography. These are called form IA (5.2s), form IB (4.9s), form II (6.7s), form III (11.3s), and form IV (13.0s). All except form III are present in significant amounts in rapidly prepared extracts and are probably native; form III is probably derived autolytically from form IV. Most of forms IA and IB can be solubilized by repeated extractions without detergent, whereas forms II, III, and IV require detergent for effective solubilization and may therefore be membrane-bound. High salt concentrations are not required for, and do not aid in, the solubilization of these forms. For all forms, molecular weights and frictional ratios have been estimated by a combination of gel permeation chromatography and velocity sedimentations in both H2O and D2O. The molecular weight estimates range from 83,000 to 357,000 and only form II shows extensive asymmetry. The separated forms have been characterized with respect to substrate affinity, substrate specificity, inhibitor sensitivity, thermal inactivation, and detergent sensitivity. Judging by these properties, C. elegans is like other invertebrates in that none of its cholinesterase forms resembles either the "true" or the "pseudo" cholinesterase of vertebrates. However, internal comparison of the C. elegans forms clearly distinguishes forms IA, III, and IV as a group from forms IB and II; the former are therefore designated "class A" forms, the latter "class B" forms. Genetic evidence indicates that separate genes control class A and class B forms, and that these two classes overlap functionally. Several factors, including kinetic properties, molecular asymmetry, molecular size, and solubility, all suggest that a molecular model of the multiple cholinesterase forms observed in vertebrate electric organs probably does not apply in C. elegans. Potential functional roles and subunit structures of the multiple AChE forms within each C. elegans class are discussed.
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PMID:Multiple molecular forms of acetylcholinesterase in the nematode Caenorhabditis elegans. 686 28

Three groups of rats were injected intraperitoneally with either parathion or paraoxon: (1) rats deprived of water for 48 hr, (2) rats allowed water ad lib but restricted in food intake to equal that consumed by water-deprived rats, and (3) controls. Following injection of parathion all groups showed a progressive decrease in enzymatic hydrolysis of acetylcholine over a 2-hr period. The decrease was significantly greater in food-restricted rats. Injection with paraoxon resulted in an immediate decrease in red cell cholinesterase activity, which remained low for 1 hr, but recovered thereafter. The esterase activity of both deprived groups was significantly lower than that of controls. These experiments suggest that persons subject to nutritional deficiency and water deficit may be abnormally susceptible to the effects of anticholinesterase pesticides.
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PMID:Water deprivation and food restriction on toxicity of parathion and paraoxon. 687 Mar 54

Diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944), a new Ca-antagonist, in the dose range of 25--200 mg/kg/day, was orally administered to Jcl:SD rats for five consecutive weeks and the following results were obtained. Neither death nor inhibition of body weight gain nor any toxic symptoms of the drug were noted in rats but an increase in water intake was found in the rats treated with over 100 mg/kg/day of KB-944. In plasma there was a decrease in alkaline phosphatase activity, creatinine level and cholinesterase activity and an increase in GPT activity and total cholesterol level in rats given a higher dosage of the drug. Weight gain of the liver, kidneys, heart, adrenals and ovaries, and degeneration in the epithelium of the renal proximal tubule were observed. However, none of these changes were serious and the maximum non-toxic dose of KB-944 was 25 mg/kg/day.
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PMID:1-month subacute oral toxicity study of KB-944, a new calcium antagonist, in rats. 689 Aug 29

Organophosphorus pesticides have generally low persistence in the environment, but they may persist in water and accumulate in certain aquatic vertebrates. Frogs are resistant to cholinesterase inhibitors; thus it was suspected that they might accumulate the pesticides. Tadpoles concentrated pesticides from water up to 60 times; those exposed to 1 ppm parathion and 5 ppm fenthion were lethal when they were fed to mallard ducks. Dicrotophos, malathion, and acephate were not accumulated to levels such that they were lethal when consumed in a single meal by ducks. Brain cholinesterase levels were correlated with dose and effect. Metabolites of parathion and fenthion produced by the tadpoles were rapidly excreted and it was concluded that they play a small role in the toxicity of the larvae to ducks. Dangerous levels of some pesticides may be accumulated by amphibians in nature and may adversely affect carnivorous species.
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PMID:Bioconcentration of organophosphorus pesticides to hazardous levels by amphibians. 696 57

Affinity electrophoresis has been applied to the analysis of the multiple molecular forms of human plasma cholinesterase allozyme U. A water-soluble p-amino-substituted-phenyltrimethylammonium polyacrylamide was synthetized by copolymerization of an unsaturated derivative of the ligand with acrylamide, and entrapped at various concentrations within the matrix of separating gels. Electrophoresis was carried out in these gels, and the relative mobility of the molecular forms of the enzyme was decreased. From the variation of mobility (Rm) as a function of immobilized ligand concentrations, the apparent dissociation constants of monomer (C1), dimer (C3) and tetramer (C4) of phenotype U were calculated. The decrease in mobility was reversed by addition of non-immobilized competitive ligands (N-methylpyridinium and N-methylacridinium). The appearance of the slopes of Rmi-1 vs. concentration does not give sufficient information for determination of the number of anionic binding sites of C4, but the slight curvature of the plots suggests that bivalent or higher interactions occur when the concentration is sufficiently high. For all three size isomers from a critical ligand concentration, a second zone, named B, appears and intensifies rapidly at the expense of the first zone (A) as the immobilized ligand concentration increases. Among several possible explanations of this phenomenon, it is proposed that the ligand induces a conformational isomerization of the enzymes with a change in affinity (KD,B less than KD,A) and that the interconversion process between the two states B in equilibrium A is slow compared with the ligand-association equilibrium dissociation steps.
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PMID:[Multiple molecular forms of human plasma butyrylcholinesterase. II.-Study of the C1, C3 and C4 components by means of affinity electrophoresis (author's transl)]. 706 31


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