Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Cholinesterase enzymes, esteratic site

Figure 6.1 Synthesis and metabolism of acetylcholine. Choline is acetylated by reacting with acetyl-CoA in the presence of choline acetyltransferase to form acetylcholine (1). The acetylcholine binds to the anionic site of cholinesterase and reacts with the hydroxy group of serine on the esteratic site of the enzyme (2). The cholinesterase thus becomes acetylated and choline splits off to be taken back into the nerve terminal for further ACh synthesis (3). The acetylated enzyme is then rapidly hydrolised back to its active state with the formation of acetic acid (4)... Figure 6.1 Synthesis and metabolism of acetylcholine. Choline is acetylated by reacting with acetyl-CoA in the presence of choline acetyltransferase to form acetylcholine (1). The acetylcholine binds to the anionic site of cholinesterase and reacts with the hydroxy group of serine on the esteratic site of the enzyme (2). The cholinesterase thus becomes acetylated and choline splits off to be taken back into the nerve terminal for further ACh synthesis (3). The acetylated enzyme is then rapidly hydrolised back to its active state with the formation of acetic acid (4)...
We may now consider in a little more detail the interaction of true (or a-) cholinesterase with acetylcholine. Wilson and Berg mann1 suggest that there are two active sites in the enzyme, known as anionic site and esteratic site respectively. These sites (represented diagrammatically in fig. II)2 are not to be considered independent. The mode of attachment will be seen to depend upon (a) the quaternary nitrogen atom (N+< ) and... [Pg.73]

Most cholinesterase inhibitors inhibit the enz)nne by acylating the esteratic site on the enzyme surface. Physostigmine and neostigmine are examples of... [Pg.63]

The enzyme cholinesterase, effecting the degradation of ACh, consists of two active sites, the anionic and the esteratic site (Figure 9.1). In the first step, ACh is attached to the anionic site and the acetyl group of the ACh molecule is transferred to the amino acid serine. The resulting serine ester is then cleaved hydrolytically and the enzyme is regenerated. ... [Pg.141]

Cholinesterase is now considered to react with substrates and competitive inhibitors by the initial formation of an enzyme affinity complex which enables the serine hydroxyl group at the esteratic site to become acylated. The acylated group can then react with any nucleophilic reagent to regenerate the free enzyme. The overall scheme is as follows ... [Pg.52]

It has already been mentioned that there are some doubts A26) about the existence of an anionic site in human or horse cholinesterase. Comparative kinetic studies using a series of pyridylcarbinol acetates as substrates have shown that acetylcholinesterase from T. marmorata electric organ and the plasma cholinesterases from horse and man have similar esteratic sites. It was also shown that the electric eel organ enzyme has an anionic site, whereas the second site of butyrylcholine... [Pg.57]

Comprehensive reviews (Kl, Ul) of the active sites of cholinesterase both postulated the presence not only of an esteratic site for butyrylcholinesterase but also of an anionic site. Additionally, in the region of the anionic site, there are two hydrophobic areas, one directly surrounding the anionic group and the second located at some distance from it (Kl). The presence of hydrophobic areas has been established (B32, C3, H29, H45, MIO) by the use of fluorescent probes with spectral responses which reflect the environment of the probe. Such probes can be used to monitor changes in the conformations of enzymes and can be designed to be active-site-directed, competitive inhibitors (H30). Aspects of the spectroscopy of intrinsic and extrinsic fluorescent probes have been reported (C3). [Pg.58]

The quaternary ammonium compound Tris [tris-(hydroxymethyl)-aminomethane] has been found to be a competitive inhibitor of horse plasma cholinesterase using butyrylcholine as substrate (P5), with inhibition occurring at concentrations commonly used in buffer solutions. Tris is believed to compete for the esteratic site but, in the absence of Mg and Ca, the enzyme was activated. The exact role of the cations was not investigated, but a complex of the cation with an amino group could be the effective inhibitor. Similar results were obtained using acetylcholinesterase from r. marmorata. [Pg.64]

Irreversible inhibitors are effectively esteratic site inhibitors which, like true substrates, react with the hydroxyl group of serine at the catalytic active site. Such inhibitors, sometimes referred to as acid-transferring inhibitors, include the organophosphates, the organo-sulfonates, and the carbamates. All form acyl-enzyme complexes which, unlike substrate-enzyme intermediates, are relatively stable to hydrolysis. Indeed, the phosphorylated enzyme intermediates have half-lives from a few hours to several days (A12), whereas the sulfonated or carbamylated enzyme complexes have much shorter half-lives—several minutes to a few hours. Several strong lines of direct evidence point to the formation of an acyl complex—the isolation of phosphorylated serine from hydrolysates of horse cholinesterase (J2), complex formation and carbamylation (02), and the sulfonation of butyrylcholinesterase by methanesulfonyl fluoride in the presence of tubocurarine and eserine (P6). [Pg.65]

Carbamates generally act quickly. They are strongly toxic to a wide range of insect pests, but have a weak effect on the red spider mite. Some of them exhibit systemic characteristics. The duration of their action varies considerably. In a similar manner to the phosporic acid esters discussed later, they exert their action by paralysing the cholinesterase enzyme. During this process, the carbamate part of the molecule is attached to the esteratic site, and the aromatic part to the anionic site of the cholinesterase enzyme. As the distance between the esteratic and anionic sites is SO nm in the cholinesterase molecule, carbamate insecticides will be most efficient if the distance between the two groups to be bound to the two sites of the enzyme is also 50 nm. (Metcalf and Fukuto, 1965 1967 Fukuto et ai, 1967). [Pg.91]

CHOLINESTERASE REACTIVATORS Although the phosphorylated esteratic site of AChE undergoes hydrolytic regeneration at a slow or negligible rate, nucleophilic agents, such as hydroxylamine (NH OH), hydroxamic adds (RCONH-OH), and oximes (RCH=NOH), reactivate the enzyme more rapidly than does spontaneous hydrolysis. Reactivation with prahdoxime (Figure 8-1E) occurs at a million times the rate of that with hydroxylamine. Several h/s-quaternary oximes are even more potent as reactivators for insectidde and nerve gas poisoning (e.g., HI-6, used in Europe as an antidote). [Pg.131]

A model of cholinesterase has been proposed that is consistent with all of the information available (Fig. 35). In the model there are two sites of attachment, an anionic site that binds the cationic quarternary nitrogen group and an esteratic site that reacts with the carbon of the carbonyl moiety of the ester. When acetylcholine is adsorbed to the enzyme, a transfer of the carbonyl group to the enzyme takes place, forming... [Pg.372]

An interaction of the esteratic site with the carbonyl carbon is supported by results of experiments with both substrates and inhibitors. A series of derivatives of nicotinic acid was found to inhibit cholinesterase. The inhibitory strength was correlated with the electrophilic character of the carbon in the order shown in (IV). The postulation of an acyl enzyme... [Pg.375]

These compoimds inhibit the hydrolysis of the neurotransmitter ACh by the enzyme AChE within the mammalian nervous system (Zwiener and Ginsburg, 1988). This inhibition causes ACh levels to rise, thus causing cholineigjc hyperstimulation at muscarinic and nicotinic receptors. There are important differences in the way carbamates and OPs bind to AChE, as well as their ability to affect the CNS. Carbamates are reversible inhibitors of cholinesterase enz3unes. Carbamates create a reversible bond to the cholinesterase enzyme through carbamylation, which can spontaneously hydrolyze and reverse the toxicity. Carbamate poisoning produces toxicity similar to that of OPs however, the toxicity is usually of a shorter duration and less severe in nature (Lifshitz et al., 1994). In contrast, OPs inhibit cholinesterase via an irreversible bond of phosphate radicals to the active esteratic site of the enzyme (Lifshitz et al., 1999). Thus, the toxicity is more severe. [Pg.1017]


See other pages where Cholinesterase enzymes, esteratic site is mentioned: [Pg.122]    [Pg.126]    [Pg.280]    [Pg.117]    [Pg.1219]    [Pg.346]    [Pg.1373]    [Pg.210]    [Pg.44]    [Pg.63]    [Pg.1054]    [Pg.156]    [Pg.189]    [Pg.52]    [Pg.57]    [Pg.58]    [Pg.62]    [Pg.569]    [Pg.172]    [Pg.27]    [Pg.376]    [Pg.376]    [Pg.235]    [Pg.1108]    [Pg.63]   
See also in sourсe #XX -- [ Pg.42 ]




SEARCH



Cholinesterase

Cholinesterases esteratic site

Enzymes cholinesterase

Esteratic site

© 2024 chempedia.info