Cholinesterase pseudo

Released ACh is broken down by membrane-bound acetylcholinesterase, often called the true or specific cholinesterase to distinguish it from butyrylcholinesterase, a pseudo-or non-specific plasma cholinesterase. It is an extremely efficient enzyme with one molecule capable of dealing with something like 10000 molecules of ACh each second, which means a short life and rapid turnover (100 ps) for each molecule of ACh. It seems that about 50% of the choline freed by the hydrolysis of ACh is taken back into the nerve. There is a wide range of anticholinesterases which can be used to prolong and potentiate the action of ACh. Some of these, such as physostigmine, which can cross the blood-brain barrier to produce central effects and neostigmine, which does not readily... 

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,... 

True and pseudo-cholinesterase. The above serum preparations contained both the true and pseudo- cholinesterases of Mendel and Rudney.1 The effect of di-isopropyl phosphorofluoridate on these components was examined separately by means of the specific substrates described by Mendel, Mundel and Rudney,2 using the titration method described above. Phosphorofluoridate (5 x 10 8m) gave an inhibition of 57 per cent of the activity towards 00045m acetylcholine, 30 per cent of the activity towards 0-0005 m acetyl-/ methyl-choline, and 40 per cent of that towards 0-005 m benzoylcholine, after incubating the enzyme with the poison for 5 min. Thus in these experiments there appeared to be no appreciable difference in sensitivity of the true and pseudo-cholinesterases of horse serum to phosphorofluoridates. 

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. 

Immediately following the injection of pseudo-cholinesterase, rabbits were protected against the effect of benzoylcholine and were unaffected by a dose of it which would normally have paralysed them. 

In Chapter in we drew attention to the fact that some nerve fibres are myelinated. It has been suggested that the pseudocholinesterase of the central nervous system may be concerned in myelin metabolism and that inhibition of pseudo-cholinesterase... 

The effectiveness of non-lethal doses of agent sarin, a strong inhibitor of both RBC (true) and plasma (pseudo) cholinesterase, was impressive (Fig. 70). In two subjects who were treated with the same dose of sarin, however, the benefit was greater in one (red) than the other (yellow). Differences in RBC cholinesterase inhibition may explain this disparity. In studies b Drs. Sidell and Aghajanian, levels of plasma cholinesterase were sometimes reduced almost to zero by sarin, without producing clinical signs of toxicity (note reversal in upper legend, which has plasma as xx and RBC as yy )-... 

As an inhibitor of plasma (pseudo) cholinesterase, DFP produced only minimal reversal of scopolamine-induced incapacitation. Note the very low plasma ChE levels, with only minor decreases in RBC ChE (Fig. 71). DFP does improve near vision when applied to the eye (David Flarper, unpublished data) suggesting that paralysis of the muscles of visual accommodation is probably peripheral in origin. Persistence of pupillary enlargement (in the face of systemic treatment with physostigmine) may be due to physiological or pK factors, causing limited access to the iris. 

It is well established that acetylcholine can be catabolized by both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) these are also known as "true" and "pseudo" cholinesterase, respectively. Such enzymes may be differentiated by their specificity for different choline esters and by their susceptibility to different antagonists. They also differ in their anatomical distribution, with AChE being associated with nervous tissue while BChE is largely found in non-nervous tissue. In the brain there does not seem to be a good correlation between the distribution of cholinergic terminals and the presence of AChE, choline acetyltransferase having been found to be a better marker of such terminals. An assessment of cholinesterase activity can be made by examining red blood cells, which contain only AChE, and plasma. 

There are two major types of cholinesterases acetylcholinesterase (AChE) and pseudocholinesterase (pseudo-ChE). AChE (also known as true, specific, or erythrocyte cholinesterase) is found at a number of sites in the body, the most important being the cholinergic neuroeffector junction. Here it is localized to the prejunctional and postjunctional membranes, where it rapidly terminates the action of synaptically released ACh. It is essential to recognize that the action of ACh is ter-... 

Pseudo-ChE (also known as butyryl-, plasma, and nonspecific cholinesterase) has a widespread distribution, with enzyme especially abundant in the liver, where it is synthesized, and in the plasma. In spite of the abundance of pseudo-ChE, its physiological function has not been definitively identified. It does, however, play an important role in the metabolism of such clinically important compounds as succinylcholine, procaine, and numerous other esters. 

Because anticholinesterase agents also inhibit plasma pseudo-ChE, they will potentiate the effects of succinylcholine by inhibiting its breakdown. This is important, for example, when succinylcholine is to be employed in patients who have previously received cholinesterase inhibitors for the treatment of myasthenia gravis or glaucoma. 

It is effective orally and resistant to pseudo-cholinesterase and possesses longer duration of action. Its nicotinic action is less than acetylcholine and actions are more marked on CVS as compared to GIT and urinary system. Earlier it was used for CVS disorders such as peripheral vascular disease and paroxysmal supraventricular tachycardia. But now, it is rarely used in therapeutics. 

The Number of Anionic Sites in True and Pseudo-Cholinesterase. 151... 

Other Views on the Difference between True and Pseudo-Cholinesterase. 154... 

Interpretation of the pS-Activity Curves of True and Pseudo-Cholinesterase. 156... 

This cholinesterase has been brought to the highest stage of purification by Edsall (4) and co-workers during their work on plasma fractionation. Pseudo-cholinesterase is contained in fraction IV-6-3 and has been obtained in crystalline form. 

An entirely different principle has been used by. Ravin et al. (9). /3-Car-bonaphthoxycholine is split by pseudo-cholinesterase into choline and /3-naphthyl hydrogen carbonate, which spontaneously decarboxylates to /3-naphthol. The latter is determined by coupling with a suitable diazonium salt to produce a colored azo dye. 

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 Pseudo-Cholinesterase of Human Plasma... 

Rivastigmine is a pseudo-irreversible inhibitor of both acetyl and butyryl cholinesterases. Thus although the drug initially blocks the enzymes, it is metabolized by them thereby giving the drug a relatively short half-life. The top dose is often necessary to achieve therapeutic efficacy, at which dose the central and peripheral cholinergic side effects become apparent. 

In Berlin in 1948, there were still incidences of malnutrition. Because of this, there were patients who suffered fatal poisoning from the generally safe, local anaestetic drug procaine. This became my impetus to study the esterase that hydrolysed procaine (9). When invited to Philadelphia, I continued these studies with the superior equipment there available to me. I found that the procaine-splitting esterase was butyrylcholinesterase, then called pseudo- or plasma-cholinesterase, and I explored a method using UV-spectrophotometry which elegantly and precisely indicated the esterase activity (10). 

According to inpatient records from St Luke s Hospital, the most common laboratory finding related to sarin toxicity was a decrease in plasma cholinesterase (ChE) levels in 74% of patients. In patients with more severe toxicity, plasma ChE levels tended to be lower, but a more accurate indication of ChE inhibition is measurement of erythrocyte ChE, as erythrocyte ChE (AChE) is considered true ChE and plasma ChE is pseudo ChE . However, erythrocyte ChE is not routinely measured, whereas plasma ChE is included in many clinical chemistry panels thus, it can be used as a simple index for ChE activity. In both the Matsumoto and Tokyo subway sarin attacks, plasma ChE served as a useful index of sarin exposure. In 92% of hospitalized patients, plasma ChE levels returned to normal on the following day. In addition, inpatient records from... 

Myers, D.K. (1952). Studies on cholinesterase - 7. Determination of the molar concentration of pseudo-cholinesterase in serum. Biochem. J. 51 303-11. 

Annapurna, V., Senciall, I., Davis, A.J., Kutty, K.M. (1991). Relationship between serum pseudo cholinesterase and triglycerides in experimentally induced diabetes mellims in rats. Diabetologia 34 320. ... 

Kusu, F., Tsuneta, T., Takamura, K. (1990). Fluorimetric determination of pseudo cholinesterase activity in postmortem blood samples. J. Forensic Sci. 35 1330. ... 

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