Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CHOLINESTERASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed2000

Cholinesterase inhibition by potato glycoalkaloids slows mivacurium metabolism.

BACKGROUND: The duration of action for many pharmaceutical agents is dependent on their breakdown by endogenous hydrolytic enzymes. Dietary factors that interact with these enzyme systems may alter drug efficacy and time course. Cholinesterases such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyze and inactivate several anesthetic drugs, including cocaine, heroin, esmolol, local ester anesthetics, and neuromuscular blocking drugs. Natural glycoalkaloid toxins produced by plants of the family Solanaceae, which includes potatoes and tomatoes, inhibit both AChE and BuChE. Here the authors assess the extent to which two solanaceous glycoalkaloids (SGAs), alpha-solanine and alpha-chaconine, can alter the effects of neuromuscular blocking drugs and cholinesterase inhibitors in vivo and in vitro. METHODS: Inhibition of purified human AChE and BuChE by SGAs, neuromuscular blocking drugs, and cholinesterase inhibitors was assessed by an in vitro colorimetric cholinesterase assay. In vivo experiments were carried out using anesthetized rabbits to test whether SGAs affect recovery from mivacurium-induced paralysis. RESULTS: SGAs inhibited human BuChE at concentrations similar to those found in serum of individuals who have eaten a standard serving of potatoes. Coapplication of SGAs (30-100 nm) with neuromuscular blocking drugs and cholinesterase inhibitors produced additive cholinesterase inhibition. SGA administration to anesthetized rabbits inhibited serum cholinesterase activity and mivacurium hydrolysis. In addition, SGA prolonged the time needed for recovery from mivacurium-induced paralysis (149 +/- 12% of control; n = 12). CONCLUSIONS: These findings support the hypothesis that inhibition of endogenous enzyme systems by dietary factors can influence anesthetic drug metabolism and duration of action. Diet may contribute to the wide variation in recovery time from neuromuscular blockade seen in normal, healthy individuals.

Animals↗
PubMed1993

The effect of cardiopulmonary bypass on cholinesterase activity.

Cholinesterase activity was determined in 18 patients who had undergone either hypothermic (n = 9) or normothermic (n = 9) cardiopulmonary bypass. The anaesthetic technique was standardised to avoid agents known to affect cholinesterase. Activity was determined in blood samples taken before the induction of anaesthesia, during cardiopulmonary bypass and for at least 7 days postoperatively. In six patients cholinesterase activity was also measured at 6 weeks postoperatively. All the patients were of normal cholinesterase genotype. In both groups cholinesterase activity fell by approximately 60% coinciding with the start of cardiopulmonary bypass, from a mean of 5976 to 2636 IU.l-1 in the hypothermic group, and from 5901 to 2615 IU.l-1 in the normothermic group (p < 0.001 in both instances) (normal range 4300-10,500 IU.l-1). Cholinesterase activity remained at this reduced level for at least 7 days postoperatively. By 6 weeks, activity had returned to within 7% of pre-induction values. There were no differences in cholinesterase activity between the hypothermic and normothermic groups at any of the sampling times.

Body Temperature↗
PubMed2000

A direct method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels.

BACKGROUND: In vertebrates, two types of cholinesterases exist, acetylcholinesterase and butyrylcholinesterase. The function of acetylcholinesterase is to hydrolyse acetylcholine, thereby terminating the neurotransmission at cholinergic synapse, while the precise physiological function of butyrylcholinesterase has not been identified. The presence of cholinesterases in tissues that are not cholinergically innervated indicate that cholinesterases may have functions unrelated to neurotransmission. Furthermore, cholinesterases display a genuine aryl acylamidase activity apart from their predominant acylcholine hydrolase activity. The physiological significance of this aryl acylamidase activity is also not known. The study on the aryl acylamidase has been, in part hampered by the lack of a specific method to visualise this activity. We have developed a method to visualise the aryl acylamidase activity on cholinesterase in polyacrylamide gels. RESULTS: The o-nitroaniline liberated from o-nitroacetanilide by the action of aryl acylamidase activity on cholinesterases, in the presence of nitrous acid formed a diazonium compound. This compound gave an azo dye complex with N-(1-napthyl)-ethylenediamine, which appeared as purple bands in polyacrylamide gels. Treating the stained gels with trichloroacetic acid followed by Tris-HCl buffer helped in fixation of the stain in the gels. By using specific inhibitors for acetylcholinesterase and butyrylcholinesterase, respectively, differential staining for the aryl acylamidase activities on butyrylcholinesterase and acetylcholinesterase in a sample containing both these enzymes has been demonstrated. A linear relationship between the intensity of colour developed and activity of the enzyme was obtained. CONCLUSIONS: A novel method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels has been developed.

Amidohydrolases↗
PubMed2006

Pharmacological characterization of orally active cholinesterase inhibitory activity of Prunus persica L. Batsch in rats.

Prunus persica L. Batsch water extract (PPE) is a potent acetylcholinesterase (AChE) inhibitor screened for the treatment of Alzheimer's disease. The effects of oral administration of the PPE were examined with comparison of those of selective butyrylcholinesterase inhibitors of 9-amino-1,2,3,4-tetrahydroacridine hydrochloride (tacrine) and tetraidopropylpyrophosphoramide (iso-OMPA) and a selective AChE inhibitor, donepezil, on the cholinesterase activity in the brain and plasma of rats. After the sequential solvent fractionation of the methanol extract of P. persica L. Batsch, the highest inhibitory fraction was that of chloroform (75%). The concentration that was required for 50% enzyme inhibition (IC(50) value) was 5.6 microg/mL for the chloroform fraction. Oral administration of PPE or tacrine caused a dose-dependent inhibition of brain and plasma cholinesterase activities. The ID(50) values of these compounds for brain cholinesterase activity were 2.7 g/kg and 8.9 mg/kg, respectively. On the other hand, the ID(50) values for plasma cholinesterase activity were 18.6 g/kg and 27.5 mg/kg, respectively. Thus, the ratios of the ID(50) (plasma < brain) were 6.0 and 3.1, respectively. These results suggest that orally administered PPE satisfactorily penetrates into the brain and inhibits cholinesterase there and that PPE is a potent inhibitor of brain cholinesterase in comparison with plasma cholinesterase in vivo.

Acetylcholinesterase↗
PubMed1982

Inhibition of human motor endplate cholinesterase by anticholinesterase compounds.

The inhibition of human motor endplate cholinesterase by anticholinesterase compounds was studied using isolated muscle membrane preparation. Ambenonium was most potent, and edrophonium was least potent in inhibiting motor endplate cholinesterase. The slope of the regression line for inhibition of motor endplate cholinesterase was greatest for ambenonium, and smallest for neostigmine and edrophonium. These compounds were less potent inhibitors of plasma cholinesterase. Ambenonium was more specific, and other compounds were less specific inhibitors of motor endplate cholinesterase. In myasthenic patients, these compounds produced adequate inhibition of motor endplate cholinesterase even in the presence of relatively mild plasma cholinesterase inhibition.

Cholinesterase Inhibitors↗
PubMed2005

Modelling the cost effectiveness of cholinesterase inhibitors in the management of mild to moderately severe Alzheimer's disease.

OBJECTIVE: To estimate the cost effectiveness (from the UK NHS and personal social services perspective) of the cholinesterase inhibitors donepezil, rivastigmine and galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer's disease. Patients had a mean age of 74 years, a mean disease duration of 1 year and a mean Alzheimer's disease assessment scale-cognitive subscale score of 24. METHODS: A pharmacoeconomic model was used to predict long-term outcomes over a 5-year time horizon and to estimate the cost effectiveness of cholinesterase inhibitors for the management of Alzheimer's disease. The model structure is informed by a systematic review of the literature on the clinical and cost effectiveness of cholinesterase inhibitors and a review of the literature on the costs and outcomes associated with treatment for Alzheimer's disease. The main outcome measure used was the cost per quality-adjusted life-year (QALY) gained. All healthcare costs (excluding cholinesterase inhibitor costs) were indexed to pounds sterling (2003 values). Drug costs are 2005 values. Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results. RESULTS: The clinical benefits on cognition from treatment with cholinesterase inhibitors resulted in an incremental cost per QALY gained ranging from 53,780 pounds sterling to 74,735 pounds sterling, over 5 years (vs usual care). Uncertainty analysis suggests that the probability of any of these treatments having an incremental cost per QALY of < 30,000 pounds sterling is < 21%. The key determinants of cost effectiveness were the effectiveness of treatment, the mean treatment cost and the cost savings associated with an expected delay in disease progression. CONCLUSIONS: Results presented in this paper suggest that the use of cholinesterase inhibitors may not be a cost-effective use of NHS resources. Guidance from the National Institute for Health and Clinical Effectiveness (NICE) in the UK on their judgements surrounding the acceptability of technologies as an effective use of resources, indicates there would need to be special reasons for accepting cholinesterase inhibitors as a cost-effective use of NHS resources.

Aged↗
PubMed2001

Pharmacodynamic-tolerability relationships of cholinesterase inhibitors for Alzheimer's disease.

According to the cholinergic hypothesis, the impairment of cognitive function and the behavioural disturbances that affect patients with Alzheimer's disease are mainly due to cortical deficiencies in cholinergic transmission. Numerous cholinesterase inhibitors have been investigated for treatment of this disease, the rationale being to support the cholinergic system by blocking the degradation of acetylcholine released from presynaptic neurons. These drugs can be classified as reversible (tacrine, donepezil and galantamine), pseudo-reversible (physostigmine, eptastigmine and rivastigmine) or irreversible (metrifonate) enzyme inhibitors. This article reviews efficacy and tolerability results from 6-month placebo-controlled studies of 7 cholinesterase inhibitors: tacrine (80 to 160 mg/day), donepezil (5 to 10 mg/day), rivastigmine (1 to 12 mg/day), metrifonate (30 to 80 mg/day), eptastigmine (30 to 60 mg/day), physostigmine (30 to 36 mg/day) and galantamine (8 to 32 mg/day). All these agents have demonstrated a statistically significant, although modest, effect versus placebo on the cognitive and global performance of patients with Alzheimer's disease. Dramatic clinical response has been seen in only 3 to 5% of patients. There are no major differences in terms of efficacy between the different drugs. The mean difference between drug and placebo effects on standardised psychometric scales is about 2 to 4 points on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog; a 70-point cognitive scale) and 0.2 to 0.5 points on the Clinician's Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus; a 7-point global scale), or 5 to 14% of the average value of the scales. The most common adverse effects observed after administration of cholinesterase inhibitors are nausea, vomiting, diarrhoea, dizziness, asthenia and anorexia, all symptoms linked to cholinergic overstimulation. These effects are dose related and largely depend on the degree of cholinesterase inhibition. Also important is the rate of onset of cholinesterase inhibition, which depends on the kinetics of enzyme inhibition, the presence and rate of titration, and the pharmacodynamic peak-to-trough fluctuations. A model predicting the incidence of nausea based on acetylcholinesterase inhibition and the half-life of acetylcholinesterase recovery is proposed. In conclusion, cholinesterase inhibitors are the only pharmacological agents proved to be effective for the treatment of Alzheimer's disease in large, long term, double-blind, placebo-controlled trials. While the efficacy of different cholinesterase inhibitors is similar, their tolerability profiles differ. For example, the incidence of nausea (in excess of that seen with placebo) at cognitively effective dosages ranges from 1% with eptastigmine 60 mg/day to 53% with physostigmine 30 mg/day. Differences in tolerability profile may be due to the extent of peripheral acetylcholinesterase inhibition needed to reach clinical efficacy. Other contributing pharmacodynamic factors are the rate of onset of and fluctuations in acetylcholinesterase inhibition at steady state.

Alzheimer Disease↗
PubMed2003

Clinically significant drug interactions with cholinesterase inhibitors: a guide for neurologists.

Cholinesterase inhibitors are the only pharmacological class indicated for the treatment of mild to moderate Alzheimer's disease. These drugs are also being used off label to treat severe cases of Alzheimer's disease or vascular dementia and other disorders. The widespread use of cholinesterase inhibitors raises the possibility of their use in combination regimens, with the subsequent risk of deleterious drug-drug interactions in high-risk populations. The purpose of this review is to present the possible sources of pharmacokinetic or pharmacodynamic drug-drug interactions involving cholinesterase inhibitors. The four cholinesterase inhibitors (tacrine, donepezil, rivastigmine and galantamine) that are currently available have different pharmacological properties that expose patients to the risk of several types of drug interactions of nonequivalent clinical relevance. The principal proven clinically relevant drug interactions involve tacrine and drugs metabolised by the cytochrome P450 (CYP) 1A2 enzyme, as well as tacrine or donepezil and antipsychotics (which results in the appearance of parkinsonian symptoms). The bioavailability of galantamine is increased by coadministration with paroxetine, ketoconazole and erythromycin. It is of interest to note that because rivastigmine is metabolised by esterases rather than CYP enzymes, unlike the other cholinesterase inhibitors, it is unlikely to be involved in pharmacokinetic drug-drug interactions. Care must be taken to reduce the risk of inducing central (excitation, agitation) or peripheral (e.g. bradycardia, loss of consciousness, digestive disorders) hypercholinergic effects via drug interactions with cholinesterase inhibitors. A review of the literature does not reveal any alarming data but does highlight the need for prudent prescription, particularly when cholinesterase inhibitors are given in combination with psychotropics or antiarrhythmics. Possible interactions involving other often coprescribed antidementia agents (e.g. memantine, antioxidants, cognitive enhancers) remain an open area requiring particularly prudent use.

Cholinesterase Inhibitors↗
PubMed2005

Evolution of clams (cholinesterase-like adhesion molecules): structure and function during development.

The protein family known as CLAMS (cholinesterase-like adhesion molecules) forms a novel class of heterophilic cell adhesion proteins. Family members are found through a wide range of metazoans and play a role during the development of multiple tissues. The majority of members of this family are transmembrane proteins with an extracellular domain that is conserved with cholinesterases including acetylcholinesterase. Yet all family members lack one or more of the residues that make up the catalytic triad necessary for enzymatic function. Therefore the conserved cholinesterase-like domain is not necessary for enzymatic function but does appear to play a role in heterophilic binding. CLAMS are expressed in a wide array of tissues and most family members appear to play a role in cell adhesion and junction formation. The development of junctions including septate junctions and synaptic junctions require CLAM family members such as Gliotactin and Neuroligins respectively. Modeling of the cholinesterase-like domain reveals that evolutionary changes to the binding pocket of the cholinesterase domain may produce a range of different ligand binding partners for CLAM family members. In this vein, previous chimera experiments and recent work has identified mutations in CLAM family members that affect the structure of the cholinesterase-like domain. These mutant forms affect protein function during the development of specialized junctions and confirm the role of the cholinesterase domain in mediating heterophilic binding.

Animals↗
PubMed2000

[Usefulness of cholinesterase determination in ascitic fluid in the differential diagnosis of ascites].

BACKGROUND: Cholinesterase is an enzyme mainly synthesized in the liver that might play a role in the differential diagnosis of ascites. We prospectively compared the sensitivity, specificity and diagnostic usefulness of the ascites cholinesterase and the classical parameters, ascites total protein concentration and serum-ascites albumin gradient in the differential diagnosis of ascites. In addition, we evaluated the relationship between those parameters and the degree of liver failure. METHODS: A total of 91 patients with ascites were analyzed. According the final diagnosis, patients were classified in two groups, patients with signs of portal hypertension [n = 78] (60 with chronic liver disease, 5 chronic liver disease and hepatocellular carcinoma, 3 chronic liver disease and spontaneous bacterial peritonitis, 3 chronic liver disease and secondary peritonitis, 7 malignancy with liver involvement) and patients with no signs of portal hypertension [n = 13] (12 patients with peritoneal neoplasia without liver involvement and 1 tuberculous peritonitis). RESULTS: The sensitivity of the test for detecting portal hypertensive ascites was lowest for ascites cholinesterase less than 600 U/L (71.7%); intermediate with ascites total protein concentration less than 25 g/l (87.2%) and highest with serum-ascites albumin gradient at least 11 g/l (93.6%). The specificity for ruling out portal hypertensive ascites was 100 percent for ascites total protein > or = 25 g/l and ascites cholinesterase > or = 600 U/L and, 76.9 percent for serum-ascites albumin gradient < 11 g/l). Diagnostic efficiency (percentage of patients accurately classified) was greater for serum-ascitis albumin gradient (91.2%; IC95: 83-95.8), and lower for ascites total protein content (89%, IC95: 80.3-94.3) and, ascites cholinesterase (75.8%; IC95: 65.5-83.9). Ascites cholinesterase showed a significant relationship (p = 0.007) with the degree of liver failure measured by Pugh's classification. CONCLUSION: Serum-ascites albumin gradient was the test with best performance characteristics to identify patients with ascites related with portal hypertension. Our results suggest that ascites cholinesterase is more associated with the degree of liver failure than with the presence of portal hypertension.

Ascites↗
PubMed1999

The effect of pesticide on the activity of serum cholinesterase and current perception threshold on the paddy farmers in the Muda agricultural development area, MADA, Kedah, Malaysia.

BACKGROUND: The aim of this study was to find out the indicator as a marker of person who are exposed to pesticides (organophospate). Up to now the serum cholinesterase is used as a marker. This new method will not taking blood vein since this be the obstacle in conducting research in a rural area. METHODS: A cross sectional study was conducted to investigate the effect of pesticide exposure on the activity of serum cholinesterase (ChE) and current perception threshold (CPT). The samples are 60 paddy farmers (exposed group) and control group taken from the office of Muda agricultural area of Kedah in 19 do not expose to pesticide. The CPT values measured using a portable constant current electric nerve stimulator, Neurometer CPT/Eagle (Neurotron Incorporated, Baltimore, USA). Assessments carried out by one examiner on the index finger (median digital nerve) and the great toe (peroneal digital nerve). The current used are 3 neuroselective frequency range 2000 Hz, 250 Hz, and 5 Hz. The serum cholinesterase activity measured spectrophotometrically using cholinesterase inhibition test kit CHE MHE 1,144729. RESULT: It was significantly evident that the serum cholinesterase activity noted reduced among the paddy farmers (p = 0.014). The CPT values were significantly elevated for the 2000 Hz frequency range for both the measurement sites (index finger p < 0.0001 and great toe p < 0.0001). For the 250 Hz frequency range CPT values were significant only for the index finger (p = 0.012). However there was no significant difference for the 5 Hz frequency range. There was also a significant correlation (negative) between CPT values and serum cholinesterase activity more for the 2000 Hz frequency range (index finger r = 0.672, p < 0.0001 & for great toe r = 0.736, p < 0.0001). The results were suggestive of subclinical impairment of distal axonopathy considering the fact only 25% of the farmer showed clinical manifestation of numbness. CONCLUSION: The selective involvement of the large diameter sensory fibres (250 Hz and 2000 Hz) were reflective of toxic peripheral neuropathy. Neurometer CPT/Eagle used as indicator for detecting the effect of pesticide instead of using cholinesterase enzyme activity.

Adult↗
PubMedDate not supplied

[The monitoring of cholinesterases in farm workers and tradesmen exposed to phosphoric esters and carbamates].

Cholinesterase (ChE) levels (Ellman method) were monitored in 90 subjects (69 males and 21 females) exposed to carbamate and organophosphate pesticides (78 agricultural workers and 12 pesticide vendors). Pre-exposure baseline values of plasma and red blood cell cholinesterase activities were defined for each subject with two blood samples (23 workers) or three blood samples (59 workers) taken almost thirty days after the last exposure. After control of intra-individual variation, 8 subjects with only one pre-exposure value and 13 with a coefficient of variation above 30% were excluded. For the other 59 subjects, the intra-individual variation of erythrocyte ChE (16%) was similar to the inter-individual one (15%), whereas the inter-individual variation of plasma ChE (21%) was higher than the intra-individual one (14%). Laboratory variation for plasma ChE measurements was 8%. Baseline values were analyzed (ANOVA) for sex, age, task and hour and season of sampling. Both erythrocyte and plasma enzymes, corrected for hematocrit, were lower in females. Plasma cholinesterase activity was lower in "re-entry" agricultural workers and in pesticide vendors. Post-exposure cholinesterase activity was measured in 54 workers within a few (1-21) days after last handling. Average relative reduction was 15.2% (95% C.I. = 4.9%-25.5%) in erythrocyte cholinesterase activity and 29.1% (95% C.I. = 18.2%-40.1%) in plasma cholinesterase activity. The one-way variance analysis showed marked plasma ChE reduction in mixers, loaders and appliers (36%, 95% C.I. = 24%-48%) and in parathion handlers (35%, 95% C.I. = 21%-49%. No significant reduction in blood cell cholinesterase activity in relation to task and to pesticide handled was observed. We conclude that the intra-individual variations of the baseline values were higher for three repetitions (88% and 84% of the population were within a variability of less than 30%, for AChE and for ChE respectively) than for two repetitions (91% and 88% of the population were within 30% of variability for AChE and for ChE respectively). The figures show a greater sensitivity of plasma ChE activity in acute exposure, probably due to a poor reliability in detection of erythrocyte ChE by local laboratories. The maximum reduction (38%, 95% C.I. = 22%-53%) in plasma ChE activity was observed within six days of the last exposure in loaders and appliers.

Agriculture↗
PubMedDate not supplied

Interactive effects of physostigmine and exercise on cholinesterase activity in red blood cells and tissues of rat.

Physostigmine is considered to be a potential pretreatment agent against organophosphate intoxication. This investigation elicits the effects of three intensities of acute exercise (50, 80 and 100% VO2max), administration of physostigmine (70 micrograms/kg, i.m.) and the combined effect of physostigmine and three intensities of acute exercise on cholinesterase activity in red blood cells and various tissues and endurance time in rats. The cholinesterase activity in red blood cells in exercised rats not exposed to physostigmine was significantly greater than that of unexercised controls (116, 112 and 108% of control, p less than 0.05, at 50, 80 and 100% VO2max, respectively) while in other tissues the cholinesterase activity in general decreased slightly. In unexercised rats given physostigmine, the cholinesterase activity ranges were 73-79, 66-68, 68-74, 67-81 and 57-61% of controls from 10-30 min in red blood cells, brain, heart, diaphragm and thigh muscle, respectively. In exercised rats exposed to physostigmine, the cholinesterase activity ranges were 54-51, 58-50, 77-73, 71-83 and 54-58% of controls from 10-30 min in red blood cells, brain, heart, diaphragm and thigh muscle, respectively. The results indicate that in control rats not given physostigmine, different intensities of acute exercise affect the cholinesterase enzyme to a moderate degree in red blood cells (p less than 0.05) and heart (p less than 0.05) without affecting brain, diaphragm and thigh muscle. Acute exercise modifies the effect of physostigmine significantly (p less than 0.01) by increasing the cholinesterase inhibition in red blood cells and brain without affecting other tissues. Exposure of rats to physostigmine (70 micrograms/kg, i.m.) increases the endurance time in rats (160-200 g weight), possibly due to peripheral vasodilatation and lowering of core temperature.

Animals↗
PubMed1989

[The preliminary investigation of cholinesterase in depression].

In this paper the activity of blood cholinesterase and serum cholinesterase were reported in 32 depressions without physical disease. There were 20 males and 12 females. Prior to study none of the patients received antidepressants, lithium and antipsychotics or other therapies. The control group consisted of 43 normal healthy persons (male: 32, female: 11). The results showed that the mean activity unit of blood cholinesterase and serum cholinesterase were lower in major depression than in the control group. Particularly more lower in the activity of blood cholinesterase in patients with very severe depression and longer course of depression. The differences were statistically significant. Based on the review of literatures, some authors suggested that the low activity of blood cholinesterase would be consistent with the hypothesis, that depression is associated with reduced cholinesterase activity in the brain. The reason for the mechanism is not clear. Whether it is a biological marker of depression, this needs further investigation.

Adult↗
PubMed1986

Biological variance of cholinesterase and 5'-nucleotidase in serum of healthy persons.

We measured cholinesterase (EC 3.1.1.8) and 5'-nucleotidase (EC 3.1.3.5) activities in serum of 24 healthy laboratory staff during 12 months. Overall mean activities ranged from 5.3 to 13.4 kU/L for cholinesterase and 5.4 to 9.8 U/L for 5'-nucleotidase. Cholinesterase activity was significantly (p less than 0.01) higher for men than for women. 5'-Nucleotidase activity was significantly (p = 0.01) higher for subjects 40 years or older than for those younger than 40, but was not different with respect to sex or time of year. Average intra- and interindividual variances (SD2) were 0.38 and 2.69 for cholinesterase and 1.41 and 0.97 for 5'-nucleotidase, respectively. Intra- to interindividual standard deviation ratios were 0.38 for cholinesterase and 1.21 for 5'-nucleotidase. Average within-run analytical variances were 0.13 and 0.3 (4% and 13% of total variance) for cholinesterase and 5'-nucleotidase, respectively. The importance of these findings in regards to diagnostic interpretation of serum cholinesterase and 5'-nucleotidase results is discussed.

5'-Nucleotidase↗
PubMed1987

Location of disulfide bonds within the sequence of human serum cholinesterase.

Human serum cholinesterase was digested with pepsin under conditions which left disulfide bonds intact. Peptides were isolated by high pressure liquid chromatography, and those containing disulfide bonds were identified by a color assay. Peptides were characterized by amino acid sequencing and composition analysis. Human serum cholinesterase contains 8 half-cystines in each subunit of 574 amino acids. Six of these form three internal disulfide bridges: between Cys65-Cys92, Cys252-Cys263, and Cys400-Cys519. A disulfide bond with Cys65 rather than Cys66 was inferred by homology with Torpedo acetylcholinesterase. Cys571 forms a disulfide bridge with Cys571 of an identical subunit. This interchain disulfide bridge is four amino acids from the carboxyl terminus. A peptide containing the interchain disulfide is readily cleaved from cholinesterase by trypsin (Lockridge, O., and La Du, B. N. (1982) J. Biol. Chem. 257, 12012-12018), suggesting that the carboxyl terminus is near the surface of the globular tetrameric protein. The disulfide bridges in human cholinesterase have exactly the same location as in Torpedo californica acetylcholinesterase. There is one potential free sulfhydryl in human cholinesterase at Cys66, but this sulfhydryl could not be alkylated. Comparison of human cholinesterase, and Torpedo and Drosophila acetylcholinesterases to the serine proteases suggests that the cholinesterases constitute a separate family of serine esterases, distinct from the trypsin family and from subtilisin.

Acetylcholinesterase↗
PubMedDate not supplied

[Reversible inhibition of cholinesterases by salts of pyrilium, thiopyrilium and selenopyrilium derivatives].

Salts of pyrilium, thiopyrilium and selenopyrilium derivatives at pH 7.5 and temperature of 25 degrees C are studied for their effect on the catalytic activity of acetyl cholinesterase (EC 3.1.1.7) of human blood erythrocytes and butyryl cholinesterase (EC 3.1.1.8) of horse blood serum which is measured by the method of potentiometric titration. All enumerated salts are established to be strong reversible inhibitors of mixed-type cholinesterases, that is testified by small values of the inhibitory constants: competitive Ki, noncompetitive K'i and generalized K epsilon. Pyrilium and selenopyrilium salts inhibit acetyl cholinesterase of human blood erythrocytes to a higher extent than butyryl cholinesterase of horse blood serum, and thiopyrilium salts inhibit the latter to the highest extent. By the value of the inhibitory effect on acetyl cholinesterase of human blood erythrocytes thiopyrilium salts exceed the analogous pyrilium salts, whereas in experiments with butyl cholinesterase of horse blood serum there is an opposite dependence.

Acetylcholinesterase↗
PubMedDate not supplied

A mathematical model for evaluating the reaction of paraoxon with human serum cholinesterase and with polymorphic forms of paraoxonase.

The inhibition of cholinesterase of human serum by paraoxon can be predicted by a mathematical model which considers two competing reactions for paraoxon: one, the direct interaction with cholinesterase, and the other, enzymatic hydrolysis by paraoxonase. On the basis of the residual cholinesterase activity at various times during the incubation with paraoxon, it is possible to determine the rate constants for the reaction of paraoxon with cholinesterase (k1), and the reaction with paraoxonase (k2), the latter being directly proportional to paraoxonase activity. The percentage of initial activity remaining as residual cholinesterase depends primarily upon the paraoxonase level; it is influenced only slightly by variations in initial cholinesterase levels within the normal range. From these results, we conclude that the residual cholinesterase activity test is, in fact, an indirect measure of serum paraoxonase activity; it has the same limitations and is no more reliable a means of differentiating individual paraoxonase genotypes than measuring the level of serum paraoxonase activity directly. Our model suggests that there are conditions where paraoxonase genotype may alter the clearance of paraoxon and in turn the reaction of paraoxon with target sites. Whether similar results would be obtained in vivo is unknown. Since this model predicts the degradation of paraoxon well in vitro, it may be possible to extend the model and predict the effect of paraoxonase genotype on the clearance of paraoxon in vivo.

Aryldialkylphosphatase↗