True cholinesterase

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

Thus a distinction was provided between simple esterases, such as fiver esterase, which catalysed the hydrolysis of simple aliphatic esters but were ineffective towards choline esters. The term 1 cholinesterase was extended to other enzymes, present in blood sera and erythrocytes of other animals, including man, and in nervous tissue, which catalysed the hydrolysis of acetylcholine. It was assumed that only one enzyme was involved until Alles and Hawes2 found that the enzyme present in human erythrocytes readily catalysed the hydrolysis of acetylcholine, but was inactive towards butyrylcholine. Human-serum enzyme, on the other hand, hydrolyses butyrylcholine more rapidly than acetylcholine. The erythrocyte enzyme is sometimes called true cholinesterase, whereas the serum enzyme is sometimes called pseudo-cholinesterase. Stedman,3 however, prefers the names a-cholinesterase for the enzyme more active towards acetylcholine, and / -cholinesterase for the one preferentially hydrolysing butyrylcholine. Enzymes of the first type play a fundamental part in acetylcholine metabolism in vivo. The function of the second type in vivo is obscure. Not everyone agrees with the designation suggested by Stedman. It must also be stressed that enzymes of one type from different species are not always identical in every respect.4 Furthermore,... 

Benzoylcholine is a substrate of pseudo-cholinesterase but not of the true cholinesterase. It inhibits the true cholinesterase of man (laked red cells centrifuged and the supernatant liquid diluted 1/150, acetylcholine substrate 0 005 m) from 30 per cent at a concentration of 0-1 M to 85 per cent at a concentration of 0-3 M. Benzoylcholine injected intravenously into rabbits will, at a dose of 8-14 mg./kg. body weight, produce a head drop lasting 40-120 sec. 

Francis placed strips of the retina from different animals in sodium sulphate to precipitate the cholinesterase in situ. Some strips were then incubated with acetylthiocholine, while others were kept in D.F.P. solution before the incubation. The tissues after preliminary washings were then treated with appropriate reagents so as to precipitate the copper derivative of thio-choline. The sections ultimately obtained showed dark deposits at those points where the enzyme was present, and deposits were absent if D.F.P. had destroyed the enzyme. As a result of the application of this technique, Francis was able to establish that for all the animals examined, except the frog, true cholinesterase was present only at the inner synaptic layer. 

Inhibition of the two principal human cholinesterases, acetylcholinesterase and pseudocholinesterase, may not always result in visible neurological effects (Sundlof et al. 1984). Acetylcholinesterase, also referred to as true cholinesterase, red blood cell cholinesterase, or erythrocyte cholinesterase is found in erythrocytes, lymphocytes, and at nerve synapses (Goldfrank et al. 1990). Inhibition of erythrocyte or lymphocyte acetylcholinesterase is theoretically a reflection of the degree of synaptic cholinesterase inhibition in nervous tissue, and therefore a more accurate indicator than pseudocholinesterase activity of inhibited nervous tissue acetylcholinesterase (Fitzgerald and Costa 1993 Sundlof et al. 1984). Pseudocholinesterase (also referred to as cholinesterase, butyrylcholinesterase, serum cholinesterase, or plasma cholinesterase) is found in the plasma, serum, pancreas, brain, and liver and is an indicator of exposure to a cholinesterase inhibitor. 

This enzyme [EC 3.1.1.7], also known as true cholinesterase, choline esterase I, and cholinesterase, catalyzes the hydrolysis of acetylcholine to produce choline and acetate. The enzyme will also act on a number of acetate esters as well as catalyze some transacetylations. 

The body contains two main classes of cholinesterase acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8).27 The former, sometimes referred to as true cholinesterase, Is mainly a tissue enzyme and Is found mainly In such tissues as the synapses of the cholinergic system It Is also found In other tissues, such as erythrocytes, where Its function Is uncertain. The latter, referred to as pseudocholinesterase, Is a soluble enzyme that is synthesized In the liver and circulates in the plasma-... 

There are two types of esterases found in animal tissues. True cholinesterase which is found in neural structures, RBC and placenta and is concerned with destruction of acetylcholine released at the nerve endings. The second type is pseudocholinesterase (non-specific cholinesterase) is found in blood serum, intestines, liver and skin and is responsible for the hydrolysis of benzoylcholine and does not hydrolyse methacholine. Cholinesterase hydrolyses acetylcholine into choline and acetic acid. 

True Cholinesterase from the Electric Organs of Electrophorus elec-... 

The electric organs of various fish are the richest source of true cholinesterase and yield very pure enzyme preparations by the method of Rothen-... 

In this respect, the most important information has been obtained from the effect of pH changes on enzymic activity. In Fig. 2 the pH-activity curves are represented for true cholinesterase (from Torpedo marmorata) and pseudo-ChE (from human serum), with ACh as substrate. The two curves are not only similar to each other, but also to the curves, characteristic for other, unspecific esterases (37). For the correct interpretation of such curves, it is important to make sure that only the protein in the... 

The Inhibitory Activity of Quaternary Ammonium Ions of the Structure RtN against True Cholinesterase of Electric Eel... 

Fig. 13. Schematic illustration of the ES complex formed by true cholinesterase with acetylcholine.

Plasma or serum cholinesterase (pseudocholinesterase) is inhibited by a munber of compounds and can also be decreased in ftie presence of liver impairment. Erythrocyte cholinesterase (true cholinesterase) reflects more accurately the cholinesterase status of the central nervous system. However, pseudocholinesterase activity responds more quickly to an inhibitor and returns to normal more rapidly than eiythrocyte-cholinesterase activity. Thus, measurement of pseudocholinesterase activity is quite adequate as a means of diagnosing acute exposure to organophosphorus compounds, but cases of illness which may be due to chronic exposure to these compounds should also be investigated by determining the erydirocyte-cholinesterase activity. A colorimetric method for this purpose has been reported (K.-B. Augustinsson et ah, Clinica chim. Acta, 1978, 89, 239-252). 

True cholinesterase (ChE). Acetylcholinesterase hydrolyzes acetylcholine within the central nervous system and peripheral neuro-effector functions. 

ACGIH TLV TWA 1 mg/m Not Classifiable as a Human Carcinogen SAFETY PROFILE Poison by ingestion, inhalation, intraperitoneal, subcutaneous, intravenous, and intramuscular routes. Moderately toxic by skin contact. Human systemic effects true cholinesterase. Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental carcinogenic and tumorigenic data. Human mutation data reported. An eye irritant. When heated to decomposition it emits very toxic fiimes of Cl" and POx. 

Pseudocholinesterase deficiency. The neuromuscular blocking action of suxamethonium is terminated by plasma pseudocholinesterase. True cholinesterase (acetylcholinesterase) hydrolyses acetylcholine released by nerve endings, whereas various tissues and plasma contain other nonspecific, hence pseudo, esterases. Affected individuals form so little plasma pseudocholinesterase that metabolism of suxamethonium is seriously reduced. The deficiency characteristically comes to light when a patient fails to breathe spontaneously after a surgical operation, and assisted ventilation may have to be undertaken for hours. Relatives of an affected individual—for this as for other inherited abnormalities carrying avoidable risk—should be sought out, checked to assess their own risk, and told of the result. The prevalence of pseudocholinesterase deficiency in the UK population is about 1 in 2500. 

Acetyl-chohnesterases (AChE, EC 3.1.1.7, also called true cholinesterase) and acylcholine acylhydrolases (or pseudocholinesterases including butyryl-cholinesterase, BuChE, EC 3.1.1.8) are commercially available enz5mies from different biological sources that catalyse the hydrolysis of acetyl- or butyryl-choline into choline and acetate or butyrate, respectively, according to the following reaction ... 

Acetylcholinesterase (AChE) (also termed true cholinesterase ) is found in the synaptic cleft of cholinergic synapses, and is of undoubted importance in regulation of neurotransmission by rapid hydrolysis of released endogenous acetylcholine (ACh). AChE is also found in erythrocytes and in the CSF, and can be present in soluble form in cholinergic nerve terminals, but its function at these sites is not clear, AChE is specific for substrates that include acetylcholine and the agents methacholine and acetylthiocholine. but it has little activity with other esters. It has a maximum turnover rate at very low concentrations of AChE (and is inhibited by high concentrations). 

Chole- Relating to the biliary system, cholestasis The failure of the normal bile flow to the intestine, causing cholestatic jaundice, cholinergic Nerve fibres that release ACETYLCHOLINE, cholinesterases Enzymes that hydrolyse choline esters, especially ACETYLCHOLINE of which there are two main forms acetylcholinesterase ( true cholinesterase ) is specific for acetylcholine, rapid in this action, and has a discrete distribution being especially located near cholinergic nerve terminals (and in erythrocytes) butyrylcholinesterase ( pseudo cholinesterase) is less selective and is able to hydrolyse some drugs (e.g. SUCCINYLCHOLINE CHLORIDE). Many drugs are known that inhibit the action of these enzymes. See anticholinesterases. chromatin A protein found in the nucleus which stains with basic dyes. It is used in the study of the behaviour of... 

Two related enzymes have the ability to hydrolyze acetylcholine. One is acetylcholinesterase (EC 3.1.1.7, acetylcholine acetyUiydrolase), which is called true cholinesterase or choline esterase I. True cholinesterase is found in erythrocytes, the lungs and spleen, nerve endings, and the gray matter of the brain. It is responsible for the prompt hydrolysis of acetylcholine released at the nerve endings to mediate transmission of the neural impulse across the synapse. The degradation of acetylcholine is required for the depolarization of the nerve so that it is repolarized in the next conduction event. 

In later reports of work using purified enzymes, it was suggested that the erythrocyte enzyme was specific for choline esters and should be called true cholinesterase, while the serum enzyme, which could also hydrolyze noncholine esters, should be called pseudocholinesterase. In fact, both enzymes are to some degree nonspecific, and these names are not recommended by the Commission on Biochemical Nomenclature of the International Union of Pure and Applied Chemistry and the International Union of Biochemistry (12). Instead, the trivial names acetylcholinesterase and cholinesterase should be used for the eiythroe) e and serum enzymes (EC 3.1.1.7 and EC 3.1.1.8, respectively). ... 

There are two main enzymes of interest. Acetylcholinesterase (AChE EC 3.1.1.7) has an affinity for the substrate acetylcholine and it is found in the erythrocytes and nervous tissue. The enzyme is sometimes referred to as true cholinesterase, and it exists in differing polymorphic forms (Skau 1985). Butyrylcholinesterase (BuChE, acylcholine acylhydrolase, EC 3.1.1.8)—also known as pseudocholinesterase or nonspecific cholinesterase— has affinities for the substrates butyrylcholine and/or pro-pionylcholine, which are dependent on the animal species (Myers 1953 Ecobichon and Comeau 1973 Scarsella et al. 1979 Unakami et al. 1987 Evans 1990 Matthew and Chapin 1990 Woodard et al. 1994). 

HUMAN TOXICITY DATA oral-man TDLo 144 mg/kg/24D intermittent toxic effect true cholinesterase oral-human LDLo 171 pg/kg sister chromatid exchange-lymphocyte 10 mg/L. 

The two cholinesterase enzymes, acetyl (AChE) and butyryl (BuChE), although closely related, show differences both in their occurrence in the body (leading to their older vernacular names of erythrocyte, red cell, or true cholinesterase in the case of AChE and plasma or pseudo-cholinestcrase for BuChE) and in their substrate specificity. AChE is more correctly called acetylcholine acetylhy-drolase (EC 3.1.1.7), and BuChE is more correctly called acylcholinc acylhydrola.se (EC 3.1.18). AChE is present in most vertebrates in several molecular forms, whereas BuChE is present in only c te, the tctramcric T form (Massoulie, 2002). 

Acetylcholinesterase An enzyme present in nerve tissue, muscles, and red blood cells that catalyzes the hydrolysis of acetylcholine to choline and acetic acid, allowing neural transmission across synapses to occur true cholinesterase. 

According to the affinity to natural substrates choline esters cholinesterases are divided into AChE and BuChE. AChE, specific or true cholinesterase, the e type of cholinesterase (EC 3.1.1.7) has a higher affinity to acetylcholine than to butyrylcholine, and splits acetyl-beta methylcholine. 

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