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)

Irreversible thermal inactivation of the tetrameric form of human plasma butyrylcholinesterase (cholinesterase; EC 3.1.1.8) was studied in water and in deuterium oxide at pH 7 in the temperature range 53-65 degrees C. The enzyme inactivation follows a complex kinetics that may be described by the sum of two apparent first-order processes. The Eyring plot for enzyme inactivation exhibits a wavelike discontinuity over a span of 2 C degrees around 58 degrees C. This transition was interpreted in terms of equilibrium between two temperature-dependent conformational states. Though 2H2O does not alter the overall multistep inactivation process, a slight solvent isotope effect was observed: a stabilizing effect and a shift in the transition temperature. A comparison between several enzyme preparations revealed differences in thermodynamic activation parameters of inactivation suggesting microheterogeneity in enzyme structures. Kinetics of inactivation of usual (E1uE1u) and atypical (E1aEa1a++) enzymes were compared. The atypical enzyme was found to be more stable than the usual phenotype.
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PMID:Stability of butyrylcholinesterase: thermal inactivation in water and deuterium oxide. 317 17

We have studied the ionic and pharmacological properties of an inward current elicited by edrophonium, a cholinesterase inhibitor, on physically isolated and internally perfused Aplysia neurons using the voltage clamp, internal perfusion and rapid external perfusion techniques. The current amplitude was dependent on the external Na concentration [(Na)o] in an almost linear manner. However, complete replacement of (Na)o with Tris or sucrose failed to abolish the current. Internal application of Na [increased (Na)i] reduced the current amplitude. In normal (Na)o, changing (Ca)o (both increases and decreases in (Ca)o) reduced the current amplitude. In the sucrose-substituted (Na)o-free condition, edrophonium still could cause a small current (less than 5% of the control). However, an increased (Ca)o did not augment this residual current. Cs and Li carried the edrophonium-activated current when substituted for (Na)o. With sucrose-substituted Na-free sea water outside, edrophonium elicited an outward current when the neuron was internally perfused with Cs, but not when the neuron was internally perfused with K. Therefore, it is unlikely that K is permeant. External application of tetrodotoxin, a blocker of voltage-dependent Na channels, external application of Cd and internal application of F did not affect the current. The edrophonium response was most sensitive to strychnine, which was about 10 times more potent than D-tubocurarine. Hexamethonium, however, had no effect. The local anesthetics, lidocaine and procaine, inhibited the response over the same concentration range as D-tubocurarine. We conclude that edrophonium opens a monocationic channel (presumably a type of Na channel) which is sensitive to (Ca)o.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of an inward current elicited by edrophonium in physically isolated and internally perfused Aplysia neurons. 319 1

The effect of bilateral nucleus basalis magnocellularis (nBM) lesions on performance in the Morris water task was examined in the rat, and the ability of anticholinesterase inhibitors to reverse the behavioral deficit was evaluated. Lesions of nBM resulted in a prolongation of escape latency. A spatial probe trial revealed that animals with sham lesions swam a greater percentage of the distance in the platform quadrant; this finding was abolished by nBM lesions. Lesions of nBM produced a nonsignificant increase in both open-field activity and activity-box scores. In Experiment 1, administration of 0.32 mg/kg physostigmine on Day 3 only resulted in a decrease in escape latency. In Experiment 2, in which cholinesterase inhibitors were administered daily for 5 days, 0.32 mg/kg but not low-dose physostigmine or two substituted N,N-alkyl phenyl carbamate cholinesterase inhibitors (RA-6 and RA-7) again improved escape latency on Day 3. Thus it was concluded that nBM lesions impair behavior on the Morris water task and physostigmine shortens escape latency.
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PMID:Effect of cholinesterase inhibitors on Morris water task behavior following lesions of the nucleus basalis magnocellularis. 321 36

The present study demonstrates that continuous administration with physostigmine salicylate (0.12 or 0.24 mg/kg/hr via mini-osmotic pumps) induces toxicities (e.g., body weight loss, decreased water consumption, tremors, decreased body temperatures, mortality) in guinea pigs. Both blood and brain cholinesterase activity is inhibited dose-dependently by physostigmine salicylate. The signs of toxicity in the guinea pigs which received the low dose appeared within 2 or 3 days and then the animals recovered, while toxic signs in the guinea pigs treated with the high dose of the drug persisted throughout the experiments. The study further shows that continuous administration of physostigmine salicylate also caused down-regulation of muscarinic receptors in the striata of the guinea pigs.
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PMID:Toxicity study of continuous administration of physostigmine salicylate. 325 Dec 46

Aldicarb, 2-methyl-2-(methylthio)propionaldehyde-O-methylcarbamoyloxime, is an oxime carbamate insecticide manufactured by the Union Carbide Corporation and sold under the trade name Temik. It is a soil-applied systemic pesticide used against certain insects, mites, and nematodes, and is applied below the soil surface for absorption by plant roots. It is generally applied to the soil in the form of 5, 10, or 15% granules, and soil moisture is essential for the release of the toxicant. Uptake by plants is rapid. Aldicarb is currently registered for use on cotton, sugar beets, sugar cane (Louisiana only), potatoes, sweet potatoes, peanuts, oranges, pecans (Southeast only), dry beans, soybeans, and ornamental plants. Home and garden use is not permitted. Discovery of aldicarb and its oxidative sulfoxide and sulfone metabolites in well or ground water in Florida, Wisconsin, and New York, and accidental poisonings from ingesting contaminated watermelons and cucumbers in the South and West have spurred interest and concern about this pesticide. The primary mechanism of toxic action of aldicarb is cholinesterase inhibition. However, unlike the relatively irreversible anticholinesterase activity of the organophosphate pesticides, the carbamylation process which produces the anti-AChE action is quickly reversible. Aldicarb is readily absorbed through both the gut and the skin, but is rapidly metabolized and excreted in the urine almost completely within 24 hr. Although it is acutely toxic to humans and laboratory animals, aldicarb is not known to be carcinogenic, teratogenic, conclusively mutagenic, or to produce other long-term adverse health effects. In cases of accidental poisoning, the cholinergic symptoms have generally subsided within 6 hr, with no side effects or complications.
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PMID:The toxicologic effects of the carbamate insecticide aldicarb in mammals: a review. 330 99

Four patients with aquagenic pruritus (AP), one patient with polycythemia rubra vera, one patient with cold urticaria, and three normal control volunteers were studied to better understand the pathophysiology of water-induced itching. Punch biopsy specimens were taken before and after water contact; the specimens were immediately frozen, sectioned, and stained histochemically for acetylcholinesterase (AChE) activity. This was localized in the nerve fibers surrounding eccrine sweat glands and was quantified by microspectrophotometry. In AP and polycythemia rubra vera after water exposure a significantly increased AChE activity suggesting acetylcholine release was observed, whereas in the patient with cold urticaria and the controls, a significant decrease was noted. Two related patients with AP had an inherited abnormality of serum cholinesterase, which, however, had no obvious correlation with their particular disease. The proof of AChE activation might support the clinical diagnosis and indicate a hypothetical involvement of eccrine sweat glands in the pathogenesis of AP.
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PMID:Aquagenic pruritus. Water-induced activation of acetylcholinesterase. 333 47

Pressure, as a perturbing variable, is one of the most powerful tools to investigate the thermodynamic parameters of chemical reactions and to study the mechanism of enzyme-catalyzed reactions. The effect of elevated hydrostatic pressure (up to 0.8 kbar) on the reaction of butyrylcholinesterase with N-methyl-(7-dimethylcarbamoxy)quinolinium was determined under single-turnover conditions at 35 degrees C. The rate of carbamylation was monitored as the accumulation of the fluorescent ion, N-methyl-7-hydroxyquinolinium, in a high-pressure stopped-flow apparatus designed for the assay of fluorescence. Elevated pressure favored formation of the enzyme-substrate complex but inhibited carbamylation of the enzyme. Because a single reaction step was recorded, it was possible to interpret the data obtained under high pressure in the form of Michaelis-Menten equations. From the pressure dependence of the dissociation constant for the enzyme-substrate complex and the rate constant for carbamylation, maximal volume changes accompanying these events were determined. The value for the binding process, delta Vb = -129 ml.mol-1, is too large to be related only to volumetric changes in the active center. Substrate-induced conformational change and change of water structure appear to be the dominant contributions to the overall volume change associated with substrate binding. The large positive activation volume measured (delta V not equal to = 119 ml.mol-1) may also reflect extended structural and hydration changes. At pressures greater than 0.4 kbar, an additional pressure effect, dependent on substrate concentration, occurred in a narrow pressure interval. This effect may have resulted from a substrate-induced pressure-sensitive enzyme conformational state.
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PMID:Effects of high pressure on the single-turnover kinetics of the carbamylation of cholinesterase. 336 37

Benzoic acid esters of various substituted 2-hydroxyacetamides (glycolamides) were found to be hydrolyzed extremely rapidly in human plasma solutions, the half-lives of hydrolysis being less than 5 s in 50% plasma solutions for some N,N-disubstituted glycolamide esters. The rapid rate of hydrolysis could be largely attributed to cholinesterase (also called pseudocholinesterase) present in plasma. From a study of a variety of substituted glycolamide esters and structurally related esters, the most prominent structural requirement needed for a rapid rate of hydrolysis was found to be the glycolamide ester structure combined with the presence of two substituents on the amide nitrogen atom. A structural similarity of such esters with benzoylcholine, a good substrate for cholinesterase, was put forward. Esters of N,N-disubstituted glycolamides are suggested to be a useful biolabile prodrug type for several carboxylic acid agents. The esters combine a high susceptibility to undergo enzymatic hydrolysis in plasma with a high stability in aqueous solution. Furthermore, as demonstrated with the benzoic acid model esters, it is feasible to obtain ester derivatives with almost any desired water solubility or lipophilicity with retainment of marked lability to enzymatic hydrolysis.
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PMID:Glycolamide esters as biolabile prodrugs of carboxylic acid agents: synthesis, stability, bioconversion, and physicochemical properties. 337 86

Adult male rats were subjected to 4 weeks' respiratory treatment with n-hexane (5000 ppm, 16h/day, 6 days/week); motor conduction velocity was significantly decreased in tail nerves at all weekly intervals and did not approach normal values in the 4 weeks following interruption of treatment. Plasma acetylcholinesterase (AChE) levels were significantly increased at all weekly intervals during treatment (25-40%); 2 weeks after the end of treatment they had returned to baseline. Oral treatment with 2,5-hexanedione (HD) (1% in drinking water) caused a similar increase in plasma levels; this increase was statistically significant also when compared with pair-fed (PF) control rats. A sucrose density gradient analysis showed only one peak of AChE activity at approximately 10 S (as in normal plasma). The levels of butyrylcholinesterase were unaltered in plasma of both n-hexane-and HD-treated rats. Both the fast-contracting EDL and the slow-contracting soleus muscles lost weight in HD-treated rats with respect to free-fed (AL) and PF controls. AChE levels responded differently to HD treatment in the two muscle types: in EDL total extracts, AChE activity increased considerably with respect to AL controls (+ 70%, p less than 0.001), while the levels of the 16 S and 4 S molecular forms were unaltered. The increased levels of AChE found in plasma of rats intoxicated with n-hexane or with its metabolite HD may originate from muscle and correspond to an increased secretion of this molecular form.
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PMID:Cholinesterases in blood plasma and tissues of rats treated with n-hexane or with its neurotoxic metabolite 2,5-hexanedione. 343 86

A sensitive method for the post-column reaction detection of organophosphorus compounds is described. The method relies on cholinesterase and is particularly suitable for the analysis of potent inhibitors such as sarin, soman and tabun. The compounds are separated by reversed-phase chromatography with methanol-water as the mobile phase in a linear gradient system. The reactor used for the detection comprises conventional autoanalyzer equipment with air segmentation of the reactor stream. The detection limits are 10 pg for sarin and soman and 60 pg for tabun. A quantitation method is presented, based on the linear correlation between the residual enzyme activity and the inhibitor concentration. The repeatability is +/- 1%. As a test of the system, the model compounds were detected against a background of urban air.
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PMID:Detector for organophosphorus compounds in liquid chromatography based on the cholinesterase inhibition reaction. 357 62


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