Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An assay for neurotoxic esterase (neuropathy target esterase, NTE) was developed by Johnson (1,2) to assess the delayed neurotoxic potential of organophosphorus compounds. NTE activity is calculated from the rate of phenyl valerate hydrolysis resistant to paraoxon and sensitive to mipafox inhibition under specified conditions of inhibitor concentrations, pH, temperature, and incubation times with inhibitors and substrate. The amount of phenol produced is measured colorimetrically after its oxidative coupling with 4-aminoantipyrine to yield 4-N-(1,4-benzoquinoneimine)-antipyrine, a chromophore with a wavelength of maximum absorbance (lambda m) 510 nm and corresponding molar absorptivity (molar extinction coefficient, epsilon) equal to 13,900 M-1cm-1. The assay was improved and simplified later by Johnson (3) without any change in the lambda m or epsilon, even though the chromophore solvent was altered by adding the detergent, sodium dodecyl sulfate (SDS). The present work demonstrates that when the NTE assay is performed according to the improved procedure, with a final [SDS] of 3.0 mg/mL, the lambda m of the chromophore in the assay mixture is shifted from 510 to 490 nm. The same shift in the chromophore lambda m is observed when phenol standards are coupled with 4-aminoantipyrine in solutions containing 3.0 mg/mL SDS. A systematic investigation of the dependence of the lambda m of the chromophore on [SDS] in the assay mixture revealed that the spectral shift increases rapidly at an [SDS] greater than the apparent critical micelle concentration (CMC; estimated to be 0.53 mg/mL under these conditions) and begins to plateau at [SDS] greater than 10 mg/mL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurotoxic esterase (NTE) assay: optimized conditions based on detergent-induced shifts in the phenol/4-aminoantipyrine chromophore spectrum. 205 50

The inhibition and the recovery of brain AChE, BuChE, and NTE activities after acute and subacute administration of DFP were studied in the rat. DFP displayed different specificities in inhibiting these enzymes; inhibition was greatest for BuChE followed by AChE and NTE. Recovery was most rapid for BuChE followed by NTE and AChE. The recovery rates of AChE and BuChE following acute and subacute treatment were similar. However, the recovery rate of NTE in subacutely treated rats was significantly faster than that in acutely treated rats. The results suggest that DFP inhibits these three enzymes and the rates of regeneration of these enzymes are significantly different.
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PMID:Effects of diisopropylfluorophosphate on brain acetylcholinesterase, butyrylcholinesterase, and neurotoxic esterase in rats. 261 Sep 46

Neurotoxic esterase (neuropathy target enzyme, NTE) is an enzyme whose irreversible inhibition is the apparent first step in the induction of organophosphorus-induced delayed neuropathy. NTE is an integral membrane protein and thus must be solubilized before isolation can be attempted. This study describes solubilization of active chicken brain NTE with the nondenaturing detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and characterization of the detergent-solubilized enzyme by gel exclusion chromatography. When detergent-solubilized membranes were chromatographed on Sepharose gel exclusion media, NTE activity eluted with an apparent molecular weight of 880-970 kD. When [3H]diisopropylphosphorofluoridate-radiolabeled membranes and unlabeled microsomal membranes were CHAPS-solubilized, combined and chromatographed on Sepharose 4B, NTE activity coeluted with two radiolabeled proteins (Mr = 148 kD and Mr = 112 kD using sodium dodecyl sulfate-polyacrylamide gel electrophoresis with reducing conditions). Another radiolabeled protein (Mr = 92 kD) coeluted exclusively with inhibitor-resistant esterase activity. This study provides strong evidence that the 148 and 112 kD proteins are subunits of a multicomponent NTE complex.
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PMID:Chromatographic characterization of neurotoxic esterase. 291 Feb 99

Organophosphorus-induced delayed polyneuropathy (OPIDP) is thought to result from organophosphorylation of neuropathy target esterase (NTE; formerly known as neurotoxic esterase), followed by an "aging" of the phosphorylated NTE. Protection against OPIDP should thus be achieved by production of an inhibited but "nonaging" NTE. Inhibited NTE produced in vitro by interaction with any of the four resolved isomers of soman aged negligibly (M. K. Johnson, D. J. Read, and H. P. Benschop, 1985a, Biochem. Pharmacol., 34, 1945-1951). Therefore both unresolved soman and the most inhibitory isomer (C(-)P(+)) were tested in adult hens for effects on NTE and for ability to produce OPIDP. With improved prophylaxis and therapy of acute intoxication, birds survived greater than 100 X LD50 of unresolved soman and did not develop OPIDP. One day after dosing, about half of brain and spinal cord NTE was in an unmodified (unaged) inhibited form; at this time eight survivors were challenged with a neuropathic dose of diisopropyl phosphorofluoridate (DFP). No neuropathy developed in four out of eight birds and mild to moderate signs were seen in the other four. Nine challenge control birds receiving DFP after solvent all developed severe neuropathy. Partial protection was seen in three out of three birds dosed prior to DFP challenge with sufficient C(-)P(+) isomer of soman (1.2 mg/kg sc) to convert about half of the spinal cord NTE to unaged inhibited form. Protection was not related to cholinergic shock. Two birds which survived out of eight pretreated with tabun (12 mg/kg sc) had about as much NTE inhibited as after soman administration but it was all in the modified (aged) inhibited form; these birds were not protected against DFP-induced neuropathy. A limited histopathologic examination showed that typical neurodegenerative lesions were seen only in birds with clear clinical neuropathy.
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PMID:High doses of soman protect against organophosphorus-induced delayed polyneuropathy but tabun does not. 334 Oct 26

The inhibitory power of organophosphorus compounds in vitro was compared against neurotoxic esterase (also known as neuropathy target esterase, NTE), acetylcholinesterase and carboxylesterase activities in brains from chickens, turkeys, quail and rats. Brains from the species most susceptible to clinical signs of organophosphorus-induced delayed neuropathy (chicken, turkey) contained more NTE than did rat and quail. Higher concentrations of organophosphorus compounds were required to inhibit rat NTE and quail acetylcholinesterase than were necessary for inhibition of these enzymes in chicken and turkey brains. Total carboxylesterase and acetylcholinesterase activities were less in rats than in the avian species.
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PMID:Comparative sensitivities of avian neural esterases to in vitro inhibition by organophosphorus compounds. 357 51

Lymphocytic NTE activity was measured after intoxication by organo phosphorus compounds and in chronic alcoholics at the beginning of alcohol withdrawal. The results showed a rapid fall in lymphocytic NTE activity; neuropathy developed when the inhibition was 75 p. 100 or more. In chronic alcoholics, the fall in NTE activity is a new concept which must be taken into account when considering the causal factors of neurotoxicity in exposed professions and in patients taking potentially neurotoxic drugs. The NTE may be a useful parameter to demonstrate the toxic origin of chronic neuropathies, especially those caused by drugs. The capacity for lymphocytic NTE activity to return to normal seems to be different in acute, compared with chronic, intoxications.
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PMID:[Determination of the neurotoxic esterase in neurologic pathology of toxic origin. Measurement in human lymphocytes in poisoning by organophosphates, ciguatera and ethyl alcohol]. 361 46

For the purpose of assessing the neurotoxic potential of organophosphorus compounds, it has been determined that paraoxon-preinhibited hen brain has both neurotoxicant (mipafox)-sensitive (neurotoxic esterase; NTE) and -insensitive esterase components. Several experiments designed to investigate the kinetic parameters governing the reaction of these esterases with two substrates and one organophosphorus inhibitor are presented. First, kinetic parameters for the hydrolysis of phenyl valerate and phenyl phenylacetate were measured. At 37 degrees C, the Km values of NTE for phenyl valerate and phenyl phenylacetate were found to be about 1.4 X 10(-3) and 1.6 X 10(-4) M respectively. At 25 degrees C, the Km of NTE for phenyl valerate was determined to be about 2.4 X 10(-3) M. Secondly, the kinetic constants of NTE for mipafox were measured at both 25 degrees C and 37 degrees C. With either phenyl valerate or phenyl phenylacetate as substrate, the Km at 37 degrees C was determined to be about 1.8 X 10(-4) M, and the phosphorylation constant (k2) was about 1.1 min-1. For phenyl valerate only, the Km at 25 degrees C was found to be about 6 X 10(-4) M, and the k2 was about 0.7 min-1. The data obtained at 25 degrees C were analysed by using a two-component model without formation of Michaelis complex, a two-component model with formation of Michaelis complex on the second component (NTE), or a three-component model without formation of Michaelis complex. The fact that the Michaelis model fit the data significantly better than either of the other two models indicates that the higher apparent Ki values that occur with low concentrations of mipafox are due to formation of Michaelis complex at high concentrations, rather than because of the presence of two NTE isoenzymes, as has been suggested by other investigators.
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PMID:Kinetics of substrate hydrolysis and inhibition by mipafox of paraoxon-preinhibited hen brain esterase activity. 375 63

A 2(3) factorial arrangement of treatments was utilized to determine effects of postweaning zeranol implantation, breed (Angus vs Limousin) and castration (bull vs steer) on growth, behavior and carcass traits. An initial slaughter group was used to account for breed differences in composition and to determine fat and lean growth in the 9-10-11th rib section (NTE). The remaining cattle were fed a finishing diet to a fat end point of .76 cm, as determined by a backfat probe. Control bulls outgained (P less than .01) control steers both to the first kill date and over the entire test and did not require significantly more time to reach the fat end point. The implant did not influence gain in bulls but did increase gain in steers. Angus and Limousins were similar in growth rate for the first 126 d before the first slaughter date. Limousins required more (P less than .01) time to reach the fat end point. Bulls and Limousins produced heavier (P less than .01) carcasses and larger rib eyes (P less than .05; bulls; P less than .01; Limousins). Steers and Angus had higher (P less than .01) marbling scores and lower bone maturity. Implanting decreased (P less than .05) marbling and increased carcass maturity. Small but significant shifts in carcass wholesale cut weight distribution were found between breed and sex condition groups. Bulls and Limousins had greater lean growth in the NTE. Bulls and steers were similar in fat growth, but Angus exceeded Limousin in this trait. Zeranol reduced scrotal circumference (P less than .01) and testicle weight at slaughter (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of zeranol implants on growth, behavior and carcass traits in Angus and Limousin bulls and steers. 404 29

Details of antigen trapping and processing in the rat lymph node have been investigated by the technique of high resolution radioautography. A series of 24 adult rats was injected with 20 microg of (125)I-labeled Salmonella adelaide flagella, given as either a primary or a secondary stimulus into one hind foot-pad. At intervals ranging from 3 min to 3 wk, rats were killed and the popliteal nodes were processed for electron microscopic radioautography using Kodak NTE emulsion. The present paper deals with events in the lymph node medulla, and an accompanying report describes the radically different behavior of antigen in the cortical follicles. In the medulla, lightly labeled granulocytes were transiently encountered, but by far the greatest bulk of antigen was in macrophages. Antigen entered these cells in two ways: by direct penetration of the plasma membrane; and by pinocytosis. In either case, the antigen rapidly became surrounded by tiny vesicles which may have represented Golgi-derived "protolysosomes." Vacuolar fusion ensued and a series of progressively larger and more complex antigen-containing "phagolysosomes" was formed. Substantial amounts of antigen could be detected in such bodies for at least 3 wk. The antigen injection, as expected, caused extensive plasma-cytopoiesis. No evidence of label in plasma cells was obtained. No special anatomic relationship between plasma cells and antigen depot sites was discovered. These results are briefly discussed in relation to current theories of immune induction.
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PMID:Antigens in immunity. XIV. Electron microscopic radioautographic studies of antigen capture in the lymph node medulla. 563 79

A calibration method is described for measuring absolute radioautographic sensitivities under various experimental conditions. Sensitivities to (3)H and (35)S radiation, i.e. ratio of developed grains to radioactive decays in the specimen, were determined with Ilford L4 and Kodak NTE emulsions. The highest values obtained in monolayers of emulsion were (1/8) for (3)H and 1/21 for (35)S. The influence of various experimental parameters on sensitivity is described, and the possibilities for quantitative electron microscope radioautography are discussed.
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PMID:Absolute sensitivity of electron microscope radioautography. 603 74


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