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)

The organophosphate cholinesterase inhibitor paraoxon is hydrolysed by serum paraoxonase/arylesterase. A genetic polymorphism of paraoxonase (PON) activity which determines high versus low paraoxon hydrolysis in human populations, may determine sensitivity to parathion poisoning. We demonstrate that arginine at position 192 specifies high activity PON whereas a glutamine specifies the low activity variant. Allele-specific probes or restriction enzyme analysis of amplified DNA allow for the genotyping of individuals. PON maps to chromosome 7q21-22, proximal to the cystic fibrosis gene, in agreement with previous genetic linkage studies.
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PMID:The molecular basis of the human serum paraoxonase activity polymorphism. 809 50

Esterases in human liver microsomes hydrolysed fluazifop-butyl (Vmax 9.8 +/- 1.6 mumol/min/g tissue), paraoxon (Vmax 47.4 +/- 7.5 nmol/min/g tissue) and phenylacetate (Vmax 57 +/- 8 mumol/min/g tissue), whereas esterases found in the human liver cytosol hydrolysed fluazifop-butyl (Vmax 10.0 +/- 0.5 mumol/min/g tissue) and phenylacetate (Vmax 37 +/- 2.9 mumol/min/g tissue) but not paraoxon. Human plasma esterase hydrolysed fluazifop-butyl (Vmax 0.09 +/- 0.006 mumol/min/mL), paraoxon (Vmax 210 +/- 14 nmol/min/mL) and phenylacetate (Vmax 250 +/- 17 mumol/min/mL). Inhibitory studies using paraoxon, bis-nitrophenol phosphate and mercuric chloride indicated fluazifop-butyl hydrolysis involved carboxylesterase in liver microsomes and cytosol, and cholinesterase and carboxylesterase in plasma. Phenylacetate hydrolysis involved arylesterase in plasma, both arylesterase and carboxylesterase in liver microsomes and carboxylesterase in liver cytosol. Plasma hydrolysis is less important and overall esterase activity is lower in humans than in the rat which is therefore a poor model.
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PMID:Human xenobiotic metabolizing esterases in liver and blood. 821 61

In a study with rats it was determined whether dietary magnesium concentration affects plasma esterase activities. The feeding of a diet with 0.01% (w/w) instead of 0.04% magnesium reduced plasma magnesium concentration by 50%. Plasma total esterase, arylesterase and butyrylcholinesterase activities were significantly decreased in the magnesium-deficient rats. In rats fed a diet containing 0.02% magnesium, plasma magnesium concentration was lowered by 30%, and group mean plasma total esterase activity was decreased, but not the activities of arylesterase and butyrylcholinesterase.
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PMID:Plasma esterase activities in rats fed magnesium-deficient diets. 826 Jul 92

In patients with hyperlipaemia, serum paraoxonase activities were polymodally distributed with 75% individuals in the low activity mode. In the same patients the distribution of serum cholinesterase activities was unimodal, but asymmetrical. Patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus had slightly higher cholinesterase activities than patients with hyperlipaemia only.
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PMID:Serum paraoxonase and cholinesterase activities in individuals with lipid and glucose metabolism disorders. 839 41

We characterized the interaction of the prodrug dipivefrin hydrochloride (DPE) with esterase activity in the rabbit cornea. The esterases which were identified included: (1) cholinesterase, (2) acetylcholinesterase, (3) a mixture containing carboxylesterase, acetylesterase and arylesterase, and (4) a non-specific esterase. DPE suppressed all of their activities as well as that of the mixture containing carboxylesterase, acetylesterase and arylesterase, and a nonspecific esterase. However, its effect on cholinesterase was larger than on any of the other activities, suggesting that DPE is a better substrate for cholinesterase than for any of the other esterases. These measurements along with those of substrate-dependent inhibition of 14C-DPE hydrolysis indicated that the DPE-esterase interaction was competitive based on changes in the apparent Km values which were extracted from Lineweaver-Burk plots of esterase activity. The substrate for cholinesterase competed with DPE most strongly among substrates. These results seem to suggest that DPE is hydrolyzed by various corneal esterases, mainly cholinesterase.
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PMID:Characterization of esterases involved in the hydrolysis of dipivefrin hydrochloride. 844 67

A novel therapy against organophosphate exposure, the combination of a carbamate eptastigmine and an organophosphate hydrolase (phosphotriesterase) was studied in mice against diisopropylfluorophosphate (DFP) (1.75 mg/kg) exposure. Mice received eptastigmine (0.9 mg/kg; iv) 10 min prior to the ip injection of DFP. Phosphotriesterase (83 U/g body weight) was injected iv 10 min after DFP. Eptastigmine (1.5 mg/kg; iv) inhibited the acetylcholinesterase activities in brain and erythrocytes for a longer time than physostigmine. Eptastigmine caused only minor changes in the behavior and activity of the animals, whereas physostigmine clearly reduced their activity for about 30 min. The eptastigmine pretreatment clearly supplemented the protective effect of phosphotriesterase against DFP: the plasma butyrylcholinesterase activity was doubled and the activity recovered faster than in animals treated with phosphotriesterase alone. In lung, butyrylcholinesterase activity was initially lower after eptastigmine-phosphotriesterase than phosphotriesterase treatment alone. However, the activity returned 24 hr later to normal in eptastigmine-phosphotriesterase-treated groups. With phosphotriesterase only, it recovered only to 75% of the control level. Presumably eptastigmine, by preventing the binding of DFP to cholinesterases, caused an elevation of free DFP levels in body fluids and promoted phosphotriesterase hydrolysis of DFP.
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PMID:Eptastigmine-phosphotriesterase combination in DFP intoxication. 888 53

The purpose of these experiments was to determine the reversibility of alpha-chaconine and alpha-solanine inhibition of human plasma butyrylcholinesterase (BuChE). For the substrate alpha-naphthylacetate, optimal assay conditions were 0.50 M sodium phosphate buffer and a substrate concentration of 3-5 x 10(-4) M. Dibucaine (1 x 10(-5) M) indicated the usual phenotype for all subjects; alpha-chaconine and alpha-solanine at 2.88 x 10(-6) M inhibited BuChE about 70 and 50%, respectively. One- and 24-hr incubations at 1 x 10(-5) M with alpha-chaconine, alpha-solanine, paraoxon, eserine, and ethanol yielded reversible inhibition with dilution except for paraoxon. Twenty-four-hour dialyses of incubations showed no inhibition except for paraoxon. PAGE enzyme activity gels of 1- and 24-hr incubations also showed no inhibition except for paraoxon. alpha-Chaconine and alpha-solanine are reversible inhibitors of human butyrylcholinesterase. At estimated tissue levels, alpha-chaconine, alpha-solanine, and solanidine inhibited BuChE 10-86%. In assays which combined alpha-chaconine, alpha-solanine, and solanidine, inhibition of BuChE was less than additive. No inhibition of albumin alpha-naphthylacetate esterase (an arylesterase) was noted with any inhibitor. The importance of these data to adverse toxicological effects of potato alkaloids is discussed.
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PMID:Inhibition of human plasma and serum butyrylcholinesterase (EC 3.1.1.8) by alpha-chaconine and alpha-solanine. 892 46

The protective action of i.v. administered eptastigmine, an organophosphate hydrolase (phosphotriesterase), or pralidoxime-2-chloride (2-PAM) and their combination in acute diisopropylfluorophosphate (DFP) intoxication were evaluated in mice. The mice received the physostigmine derivative, eptastigmine (0.9 mg/kg body wt, i.v.), 10 min prior to the i.p. injection of DFP (1.8 mg/kg body wt). Phosphotriesterase (66 micromol/min x ml/g and 6 microg/g body wt) or 2-PAM (30 mg/kg body wt) were given i.v. 30 min after DFP. The animals also received atropine sc (37.5 mg/kg body wt) immediately after DFP. The cholinesterase (ChE) activities were not protected or reactivated by 2-PAM alone. The ChE activities in brain and plasma were protected by phosphotriesterase. Eptastigmine alone assisted the recovery of the brain ChE activities. Also the combination of eptastigmine-phosphotriesterase protected the brain enzymes. It did not, however, provide any additional protection compared with phosphotriesterase-treatment on its own. In brain, the combination of eptastigmine with 2-PAM resulted in partly restored enzyme activities 24 hr after DFP exposure. In plasma, eptastigmine did not prevent the inhibition of ChE by DFP. However, when it was combined with phosphotriesterase, it significantly promoted the recovery of plasma ChE activity. In lung and in erythrocytes, the various combinations of antidotes caused only minor changes in the ChE activities.
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PMID:Phosphotriesterase, pralidoxime-2-chloride (2-PAM) and eptastigmine treatments and their combinations in DFP intoxication. 897 81

Previously Haley et al. described six possible syndromes identified by factor analysis of symptoms in Gulf War veterans and demonstrated that veterans with these symptom complexes were more neurologically impaired than age-sex-education-matched well controls. They also uncovered strong associations (relative risks 4-8) suggesting that these symptom complexes were related to wartime exposure to combinations of organophosphate pesticides, chemical nerve agents, high concentration DEET insect repellant, and symptoms of advanced acute toxicity after taking pyridostigmine. Here we have shown that compared to controls, ill veterans with the neurologic symptom complexes were more likely to have the R allele (heterozygous QR or homozygous R) than to be homozygous Q for the paraoxonase/arylesterase 1 (PON1) gene. Moreover, low activity of the PON1 type Q (Gln192, formerly designated type A) arylesterase allozyme distinguished ill veterans from controls better than just the PON1 genotype or the activity levels of the type R (Arg192, formerly designated type B) arylesterase allozyme, total arylesterase, total paraoxonase, or butyrylcholinesterase. A history of advanced acute toxicity after taking pyridostigmine was also correlated with low PON1 type Q arylesterase activity. Type Q is the allozyme of paraoxonase/arylesterase that most efficiently hydrolyzes several organophosphates including sarin, soman, and diazinon. These findings further support the proposal that neurologic symptoms in some Gulf War veterans were caused by environmental chemical exposures.
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PMID:Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. 1037 7

A direct continuous spectrophotometric assay to measure pyrethroid-cleaving enzymes in human serum was developed using cis- and trans-alpha-naphthyl-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (cis- and trans-naphthyl-Cl2CA). These substrates show a structure very similar to the pyrethroids most often used (e.g. permethrin, cyfluthrin). The method is based on an increase in absorbance at 321 nm which occurs with the hydrolysis of the alpha-naphthyl esters to alpha-naphthol. The assay was optimised regarding type of buffer, pH and substrate concentrations, it was linear for at least 10 min at 37 degrees C. These esterases were completely inhibited by bis-(4-nitrophenylphosphate), a specific carboxyesterase inhibitor. They displayed a great individual variability in human serum, activities were between less than 40 and 1000 U/l for cis-naphthyl-Cl2CA, between less than 40 and 2000 U/l for trans-naphthyl-Cl2CA, respectively. However, a correlation of enzyme activity to sex or age could not be observed. Furthermore, the activity of pyrethroid-cleaving esterases did not correspond to the activities of acylesterase, arylesterase, acetylcholinesterase or butyrylcholinesterase.
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PMID:A spectrophotometric assay for pyrethroid-cleaving enzymes in human serum. 1041 80


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