Esterases acetylcholin esterase

Application of the CCM to small sets (n < 6) of enzyme inhibitors revealed correlations between the inhibitory activity and the chirality measure of the inhibitors, calculated by Eq. (26) for the entire structure or for the substructure that interacts with the enzyme (pharmacophore) [41], This was done for arylammonium inhibitors of trypsin, Di-dopamine receptor inhibitors, and organophosphate inhibitors of trypsin, acetylcholine esterase, and butyrylcholine esterase. Because the CCM values are equal for opposite enantiomers, the method had to be applied separately to the two families of enantiomers (R- and S-enantiomers). 

Katz E, WiUner 1, Wang J (2004) Electroanalytical and bioelectroanalytical systems based on metal and semiconductor nanoparticles. Electroanalysis 16 19-44 Pardo-Yissar V, Katz E, Wasserman J, Willner 1 (2003) Acetylcholine esterase-labeled CdS nanoparticles on electrodes Photoelectrochemical sensing of the enzyme inhibitors. J Am Chem Soc 125 622-623... 

Diol bonded silica Glucosamine, bovine serum albumin, immunoglobulin, acetylcholine esterase, horse liver alcohol dehydrogenase [136]... 

Pontine cholinergic agonists and acetylcholine esterase inhibitors... 

Trettnak W., Reininger F., Zinterl E., Wolfbeis O.S., Fiber Optic Remote Detection of Pesticides and Related Inhibitors of the Enzyme Acetylcholine Esterase, Sensor Actuat B-Chem 1993 11 87. 

A particular interest for clinical applications was a possibility for detection of dopamine by its oxidation on nickel [19], cobalt [65], and osmium [66] hexacyanofer-ates. Except for oxidation of dopamine, cobalt and osmium hexacyanoferrates were active in oxidation of epinephrine and norepinephrine. For clinical analysis it is also important to carry out the detection of morphine on cobalt [67] and ferric [68] hexacyanoferrates, as well as the detection of oxidizable amino acids (cystein, methionine) by manganous [69] and ruthenium [70] hexacyanoferrate-modified electrodes. In general, oxidation of thiols was first shown for Prussian blue [71] and nickel hexacyanoferrate [72], This approach has been used for the detection of thiols in rat striatum microdialysate [73], Alternatively, the detection of thiocholine with Prussian blue was employed for pesticide determination in acetylcholine-esterase test [74],... 

Tor [7] developed a new method for the preparation of thin, uniform, self-mounted enzyme membrane, directly coating the surface of glass pH electrodes. The enzyme was dissolved in a solution containing synthetic prepolymers. The electrode was dipped in the solution, dried, and drained carefully. The backbone polymer was then cross-linked under controlled conditions to generate a thin enzyme membrane. The method was demonstrated and characterized by the determination of acetylcholine by an acetylcholine esterase electrode, urea by a urease electrode, and penicillin G by a penicillinase electrode. Linear response in a wide range of substrate concentrations and high storage and operational stability were recorded for all the enzymes tested. 

The same group reported in 1986 a sensitive and selective HPLC method employing CL detection utilizing immobilized enzymes for simultaneous determination of acetylcholine and choline [187], Both compounds were separated on a reversed-phase column, passed through an immobilized enzyme column (acetylcholine esterase and choline oxidase), and converted to hydrogen peroxide, which was subsequently detected by the PO-CL reaction. In this period, other advances in this area were carried out such as the combination of solid-state PO CL detection and postcolumn chemical reaction systems in LC [188] or the development of a new low-dispersion system for narrow-bore LC [189],... 

Choline, acetylcholine Choline oxidase Acetylcholine esterase 48-50... 

Sanders They release acetylcholine to the same extent. We measured the output of acetylcholine from the nerves, and this was the same in wild-type and mutant animals. It appears that the close association between the nerve terminals and the interstitial cells is very important. As acetylcholine is released, it is broken down by the esterase. If the esterase is inhibited, a response in the smooth muscle can be seen, but this is not physiological. 

Hirst We can demonstrate that the nerves are releasing acetylcholine. If we block the esterases we get a slow response in the muscle. The acetylcholine can get there it just doesn t normally get there. 

Sanders The esterase destroys acetylcholine as an effective agonist, so you can still see the consequences of acetylcholine release by measuring tritiated choline, but it is not an effective agonist. 

A variety of enzymes (such as acetylcholine esterase, Porcine pancreatic lipase, Pseudomonas cepacia lipase, and Candida antarcita lipase) have been found useful in the preparation of enantiomerically pure cyclopentenol (+)-2 from 1. The enantiomeric (—)-2 has been prepared from diol 4 by enzymatic acetylation catalyzed by VP-345 with isopropenyl acetate in an organic medium. The key intermediate cyclopentanones (+)-6, (—)-6, 7, and 8, which are useful in the preparation of many bioactive molecules, can be obtained from 3 and 5 via routine chemical transformations.7... 

There is some confusion in the literature regarding the substances designated as anti-choline-esterases (usually shortened to anticholinesterases). The term cholinesterase was first used1 in connexion with an enzyme present in the blood serum of the horse which catalysed the hydrolysis of acetylcholine and of butyrylcholine, but exhibited little activity towards methyl butyrate,... 

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,... 

Brzezinski J, Ludwicki K. 1973. The interrelationship of the changes of acetylcholine esterase and catecholamines blood and urine levels in rats poisoned with Disyston. Pol J Pharmacol Pharm 25 313-316. 

The work that paved the way toward enzymatic inhibition was published in the early 1990s by Wudl and coworkers (Schinazietal., 1993 Friedmanetal., 1993 Sijbesma et al., 1993) and since then studies regarding antiviral activity, mainly HIV-protease inhibition, have been carried out to find active compounds. Up to now, the most effective fullerene derivatives are the trans-2, -dimethy 1-bis-fulleropyrrolidin-ium salt (Fig. 1.4) (Marchesan et al., 2005) and the dendrofullerene reported by Hirsch (Schuster et al., 2000) both of them present an ECJ0 of 0.2pM. Also HIV reverse transcriptase can be inhibited by, -dimcthyl-bis-fulleropyrrolidinium salts (Mashino et al., 2005). The same compounds are also active against acetylcholine esterase (AChE), an enzyme that hydrolyzes a very important neurotransmitter. 

Aeetylacetone, 32 248-249 hydrogenation, 32 259-262 Acetylcholine esterase, 20 344, 367 Acetylene adsorption complexes, 31 6-7 potential dependence, 30 258 catalytic oxidation of, for oxygen manufacture, 3 107... 

The most outstanding example illustrating this strategy came from the team of Alain Friboulet and Daniel Thomas, who produced anti-idiotype antibodies against a monoclonal antibody AE2 that was a competitive inhibitor of acetylcholine esterase. One of the selected antibodies, 9A8, catalyzes the hydrolysis of acetylthio-choline with a pseudo first-order rate constant /feat = 81 and a factor of acceleration of 4.2 x 10 . These remarkable parameters, which are only two orders of magnitude lower when compared to those of the enzyme, make abzyme 9A8 the most powerful abzyme known until now. 

Through its structural similarity to acetylcholine (Figure 3.7b), muscarine binds to the acetylcholine receptor on the synapses of nerve endings of smooth muscles and endocrine glands, causing the well-known parasympaticomimetic effects. Because muscarine is not an ester like acetylcholine, and hence resists esterase activity, it is not degraded and so can cause continuous stimulation of the affected neurons. 

Acetylcholine is a relatively small molecule that is responsible for nerve-impulse transmission in animals. As soon as it has interacted with its receptor and triggered the nerve response, it must be degraded and released before any further interaction at the receptor is possible. Degradation is achieved by hydrolysis to acetate and choline by the action of the enzyme acetylcholinesterase, which is located in the synaptic cleft. Acetylcholinesterase is a serine esterase that has a mechanism similar to that of chymotrypsin (see Box 13.5). 

The mode of action of the isobutylamides is unknown, although Miyakado et al. found that several isobutylamides (i.e. pipercide and related compounds) caused repetitive discharge when the nerve cord of the cockroach, Periplaneta americana was stimulated. We found that fagaramide was inactive as an acetylcholine esterase inhibitor in an m vitro assay(unpublished dat a). 

The special case of the endogenous transmitter acetylcholine illustrates well the high velocity of ester hydrolysis. Acetylcholine is broken down at its sites of release and action by acetylcholinesterase (pp. 100,102) so rapidly as to negate its therapeutic use. Hydrolysis of other esters catalyzed by various esterases is slower, though relatively fast in comparison with other biotransformations. The local anesthetic, procaine, is a case in point it exerts its action at the site of application while being largely devoid of undesirable effects at other locations because it is inactivated by hydrolysis during absorption from its site of application. 

Lin BQ, Ji H, Li P, Fang W, Jiang Y, Inhibitors of acetylcholine esterase in vitro screening of steroidal alkaloids from Fritillaria species, Planta Afc 72 814—818,... 

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