Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mipafox administered to rats daily for 35 days produced ataxia and a reduction in the level of dopamine in the corpus striatum. Treatment with Leptophos for the same period produced slight motor dysfunction and a small but significant reduction in the level of striatal dopamine. Fenitrothion neither produced motor dysfunction nor changed the level of striatal dopamine. The cholinesterase activity of corpus striatum was inhibited by all the compounds. The results suggest the possible involvement of striatal dopamine in the delayed neurotoxic effects of certain organophosphorus compounds.
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PMID:Role of striatal dopamine in delayed neurotoxic effects of organophosphorus compounds. 5 73

Human erythrocytes contain a butyrylesterase which, judging from the ease with which it can be solubilized, is present in the cytoplasm of these cells. This enzyme has been isolated and a number of its properties characterized. The purified enzyme hydrolyzed butyryl esters with both a lower Km and higher V than is seen with esters containing longer or shorter acyl groups. It has a molecular weight of 320 000 and an isoelectric point of 4.1. This low isoelectric point is apparently a result of the relatively high content of glutamic and aspartic acids. The stability of the isolated butyrylesterase has been examined under a number of different conditions. The enzyme is inhibited by low concentrations of Hg2+, Cd2+, Zn2+ and the organophosphorus compound Mipafox, but is insensitive to eserine. The properties of this butyrylesterase, including its ability to hydrolyze thiocholine esters at a relatively rapid rate (albeit with a high Km), are a mixture of those expected for an arylesterase and a cholinesterase.
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PMID:Isolation and characterization of a butyrylesterase from human erythrocytes. 48 6

Cholinesterases of porcine left ventricular heart muscle were characterized with respect to substrate specificity and inhibition kinetics with organophosphorus inhibitors N,N'-di-isopropyl-phosphorodiamidic fluoride (Mipafox), di-isopropylphosphorofluoridate (DFP), and diethyl p-nitro-phenyl phosphate (Paraoxon). Total myocardial choline ester hydrolysing activity (234 nmol/min/g wet wt with 1.5 mM acetylthiocholine, ASCh; 216 nmol/min/g with 30 mM butyrylthiocholine, BSCh) was irreversibly and covalently inhibited by a wide range of inhibitor concentrations and, using weighted least-squares non-linear curve fitting, residual activities as determined with four different substrates in each case were fitted to a sum of up to four exponential functions. Quality of curve fitting as assessed by the sum of squares reached its optimum on the basis of a three component model, thus, indicating the presence of three different enzymes taking part in choline ester hydrolysis. Final classification of heart muscle cholinesterases was obtained according to both substrate hydrolysis patterns with ASCh, BSCh, acetyl-beta-methylthiocholine and propionylthiocholine, and second-order rate constants for the reaction with organophosphorus inhibitors Mipafox, DFP, and Paraoxon. One choline ester-hydrolysing enzyme was identified as acetylcholinesterase (EC 3.1.1.7), and one as butyrylcholinesterase (EC 3.1.1.8). The third enzyme with relative resistance to organophosphorus inhibition was classified as atypical cholinesterase.
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PMID:Cholinesterases of heart muscle. Characterization of multiple enzymes using kinetics of irreversible organophosphorus inhibition. 154 Feb 36

A case of 38 year old man who worked with organochlorinated and Parathion during 5 years is reported. His follow-up was up to 2 years. The onset of the disease was characterized by cholinergic signs, headache, loss of weight, trembling, miokimias, fasciculations, ataxia, myotonic phenomena (in hands only) and motor sensitive peripheral polyneuropathy (affecting the lower limbs symmetrically). Low concentrations of blood cholinesterases confirmed the etiology. Myotonic phenomena disappeared spontaneously 6 months after the initial observation. One year later, the concentration of erythrocyte acetylcholinesterase was found to be low and plasma cholinesterase was normal, suggesting that the patient was carrier of a congenital deficiency of acetylcholinesterase. In literature relationship between myotonia and intoxication due to organophosphorus was not found. The whole clinical picture, cholinergic symptoms, transitory phenomena and spontaneous motor activity could be explained by an excess of acetylcholine. Electromyography (EMG) in the first observation showed neuromuscular transmission blocking characterized by deficiency or absence of voluntary activity, unexcitability of fibular nerves, with fibrillations and positive peaks as described previously with Mipafox (another organophosphorus agent). During 2 years of observation numerous end-plates potentials of muscular fibres persisted in the EMG. A progressive increase in voluntary activity showed by unit motor potential of almost normal amplitude and very increased duration was observed. No potentials of reinnervation were noted. The results of EMG were explained as disturbances of neuromuscular transmission associated with moderate signs of denervation. The Eaton-Lambert's test and the stimulation of a single unit motor potential confirmed disorder of neuromuscular synapses. The histochemistry of brachial biceps showed scattered atrophic and angulated type I and II fibres. Teased-fibres preparations showed nerve fibres with B, C, and G alterations as defined by Dyck et al. indicating axonal degeneration. These results were according to velocity of sensitive conduction. The conduction velocity of fibular nerves was strongly delayed during all the evolution indicating serious disorders of motor nerves myelin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Polyneuropathy caused by parathion: clinical, electrophysiologic and histologic studies of a case]. 665 78

Cholinesterases in hen brain were characterized with respect to inhibition kinetics and substrate specificity. Three organophosphorus inhibitors were used: diethyl p-nitrophenyl phosphate (Paraoxon, E 600), di-isopropylphosphorofluoridate (DFP), and N,N'-di-isopropylphosphorodiamidic fluoride (Mipafox). The kinetics of irreversible cholinesterase inhibition were studied using two substrates, acetylthiocholine and butyrylthiocholine. The inhibition curves were analysed by the method of iterative elimination of exponential functions. Final classification of the different enzymes was done by combining two inhibitors in sequential inhibition expts. Six cholinesterases were shown to hydrolyse choline esters in hen brain, one was identified as acetylcholinesterase (EC 3.1.1.7) and one as cholinesterase (EC 3.1.1.8). Four enzymes can be classified as intermediate type cholinesterases according to their substrate specificity and to their inhibition constants. The possible role of different brain cholinesterases for the development of atypical symptoms following organophosphate intoxication is discussed.
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PMID:Brain cholinesterases. Differentiation of target enzymes for toxic organophosphorus compounds. 687 Sep 9

The actions of both reversible and irreversible anticholinesterase drugs on the nerve-free smooth muscle of the chick amnion are described. The tertiary compound physostigmine and the irreversible inhibitor diisopropylfluorophosphonate were found to be active in causing contractions, whereas the quaternary compound neostigmine and the irreversible inhibitor Mipafox were only slightly active in this respect. Manometric studies showed that all four compounds were highly active, however, in inhibiting the cholinesterase found in the chick amnion. The effects produced by these compounds in the organ bath are thought to be due to the accumulation of endogenously produced acetylcholine within the tissue. Evidence for an intracellular action of endogenously produced acetylcholine in the smooth muscle of the chick amnion is discussed.
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PMID:Actions of some anticholinesterases on the smooth muscle of the chick amnion. 1388 99

Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition MCP is a reversible inhibitor of cholinesterases from human central nervous system and blood. Metoclopramide may have a cholinesterase protective effect against inhibition by organophosphates. The purpose of the study was to quantify in vitro, by means of the IC(50) shift, the extent of MCP conferred protection, using mipafox (MPFX) as an inhibitor. Mipafox is a neuropathic organophosphate. Cholinesterase activities (with acetylthiocholine [ChE-A] and butyrylthiocholine [ChE-B] as substrates) in human plasma were measured photometrically in the presence of different MPFX concentrations and the IC(50) was calculated. Determinations were repeated in the presence of increasing MCP concentrations. It appears that the shift induced by the presence of MCP increases with the MCP concentration in a linear manner. In the presence of a clinically easily achievable plasma concentration of 1 micro M MCP, the IC(50) of MPFX for cholinesterase 'shifts' by a factor of ca. 3-6. The protective effect of MCP on cholinesterase could be of practical relevance in the treatment of organophosphate poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted.
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PMID:In vitro protection of plasma cholinesterases by metoclopramide from inhibition by mipafox. 1505 10