Esterases cholinesterase

C-type esterases (cholinesterase EC 3.1.1.7 EC 3.1.1.8) they are most active on choline esters but hydrolyse some aromatic and aliphatic esters slowly they are inhibited by organophosphates. 

One of the most important hydrolases is acetylcholine esterase (cholinesterase). Acetylcholine is a potent neurotransmitter for voluntary muscle. Nerve impulses travel along neurons to the synaptic cleft, where acetylcholine stored in vesicles is released, carrying the impulse across the synapse to the postsynaptic neuron and propagating the nerve impulse. After the nerve impulse moves on, the action of the neurotransmitter molecules must be stopped by cholinesterase, which hydrolyzes acetylcholine to choline and acetic acid. Some dangerous toxins such as the exotoxin of Clostridium botulinum and saxitoxin interfere with cholinesterase, and many nerve agents such as tabun and sarin act by blocking the hydrolytic action of cholinesterase, see also Enzymes Hydrolysis. 

See also A-Esterases Cholinesterase Inhibition Organophosphate Poisoning, Delayed Neurotoxicity Organophosphates. 

See also Acetylcholine A-Esterases Cholinesterase Inhibition Neurotoxicity Organophosphate Poisoning, Intermediate Syndrome Organophosphates. 

In certain regions of the biosphere are localized esterases possessing a more marked specificity chlorophyllase, pectin-esterases, cholinesterases, etc. 

Cholinesterases are another group of B-esterases. The two main types are acetylcholinesterase (EC 3.1.1.7) and unspecific or butyrylcholinesterase (EC 3.1.1.8). Acetylcholinesterase (AChE) is found in the postsynaptic membrane of cholinergic... 

Cholinesterase (ChE) A general term for esterases that hydrolyze cholinesters. 

The mechanism of OPIDN is poorly understood, but, since all organophosphate esters that produce OPIDN are either direct cholinesterase inhibitors or are metabolically converted to cholinesterase inhibitors, inhibition of an esterase of some kind has generally been thought to be involved (Baron 1981). Certain... 

FMC. 1991a. The effects of Durad 125 on serum cholinesterase and brain neuropathy. Target esterase activity in male Long-Evans rats. Study No 64460. FMC Corporation, Princeton, NJ. 

Some OP compounds induce delayed neurotoxic effects ("delayed neuropathy") after acute poisoning. This delayed neurotoxic action is independent of cholinesterase inhibition but related to phosphorylation of a specific esterasic enzyme in the nervous tissue, called "neurotoxic esterase" or "neuropathy target esterase" (NTE) (Johnson, 1982). NTE is present in the nervous tissue, liver lymphocytes, platelets, and other tissues, but its physiological function is unknown. There is a rather large inter-individual variation of lymphocyte and platelet NTE activity (Table 2). 

In AChE-based biosensors acetylthiocholine is commonly used as a substrate. The thiocholine produced during the catalytic reaction can be monitored using spectromet-ric, amperometric [44] (Fig. 2.2) or potentiometric methods. The enzyme activity is indirectly proportional to the pesticide concentration. La Rosa et al. [45] used 4-ami-nophenyl acetate as the enzyme substrate for a cholinesterase sensor for pesticide determination. This system allowed the determination of esterase activities via oxidation of the enzymatic product 4-aminophenol rather than the typical thiocholine. Sulfonylureas are reversible inhibitors of acetolactate synthase (ALS). By taking advantage of this inhibition mechanism ALS has been entrapped in photo cured polymer of polyvinyl alcohol bearing styrylpyridinium groups (PVA-SbQ) to prepare an amperometric biosensor for... 

Esterases that contribute to human drug metabolism fall into three major classes the cholinesterases (acetylcholinesterase, pseudocholinesterase, butyrylcholinesterase, etc.),... 

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,... 

The enzyme responsible for the reaction is insensitive to fluoride, and it is not related to phosphatase, cholinesterase or esterase.2... 

The enzymes used by these workers were cholinesterase, prepared from horse serum, and horse-liver esterase. Parallel experiments were carried out with twice crystallized ovalbumin, and with an aged, dialysed specimen of horse serum with negligible esterase activity. 

The reaction conditions with cholinesterase and the esterase were in each case sufficient to produce a reduction in enzyme activity greater than 98 per cent. 

Lord and Potter1 have claimed that it is important not to generalize the known anti-cholinesterase activity of organo-phosphorus insecticides in mammals to account for their action in insects. They could find no specific cholinesterase in two species of insect, but there was a general esterase inhibited by the insecticides. 

In this connexion we will stress again that, although there is often a correspondence between toxic action of organo-phosphorus insecticides and anti-cholinesterase activity (p. 67), the relationship is not always simple. Thus parathion (p. 178), not itself an esterase inhibitor, is converted in vivo into an enzyme inhibitor.1 On the other hand, Aldridge2 has shown that the inhibitor paroxan can be hydrolysed enzymically to produce non-inhibitory substances. 

We must stress that organo-phosphorus compounds are not specific inhibitors for the cholinesterases, but are rather inhibitors for enzymes possessing carboxylic esterase activity. All the enzymes mentioned below will hydrolyse carboxylic esters. However, not all esterases are inhibited, for example, A-esterase which hydrolyses phenyl acetate is not inhibited by organo-phosphorus compounds. 

Carboxylesterases (EC 3.1.1.1) can be detected in most mammalian tissues. Besides organs with high carboxylesterase activity such as liver, kidney, and small intestine, esterase activity is present, e.g., in the brain, nasal mucosa, lung, testicle, and saliva. Compared to rat plasma, human plasma contains little carboxylesterase, its esterase activity being essentially due to cholinesterase [61][73][79][89-91],... 

In contrast to acetylcholinesterase, cholinesterase (acylcholine acyl-hydrolase, butyrylcholinesterase, EC 3.1.1.8) exhibits relatively unspecific esterase activity toward choline esters, with abroad specificity relative to the size of the acyl group. The enzyme is synthesized in the liver and can be found in smooth muscle, adipocytes, and plasma. Its physiological role remains partly obscure, but there is evidence that it is present transiently in the embryonic nervous system, where it is replaced in later stages of development by acetylcholinesterase. It has, therefore, been suggested that cholinesterase functions as an embryonic acetylcholinesterase. 

C. H. Walker, H. M. Thompson, Phylogenetic Distribution of Cholinesterases and Related Esterases , Chem. Agric. 1991, 2, 1-17. 

Other serine hydrolases such as cholinesterases, carboxylesterases, lipases, and fl-lactamases of classes A, C, and D have a hydrolytic mechanism similar to that of serine peptidases [25-27], The catalytic mechanism also involves an acylation and a deacylation step at a serine residue in the active center (see Fig. 3.3). All serine hydrolases have in common that they are inhibited by covalent attachment of diisopropyl phosphorofluoridate (3.2) to the catalytic serine residue. The catalytic site of esterases and lipases has been less extensively investigated than that of serine peptidases, but much evidence has accumulated that they also contain a catalytic triad composed of serine, histidine, and aspartate or glutamate (Table 3.1). 

Semm albumin is not an enzyme but a transport protein, yet it has demonstrated hydrolytic activity against a variety of xenobiotic substrates. This este-rase-like activity has been known for years, but there is still confusion in the literature regarding its nature and mechanism. Indeed, it was not clear whether this activity is intrinsic to the albumin molecule or results from contamination of albumin preparations by one or more hydrolytic enzymes. More-recent studies with highly purified human serum albumin (HSA) have confirmed that the protein has an intrinsic esterase activity toward several substrates, but that activity due to contaminants and particularly semm cholinesterase is involved... 

Whereas the above evidence clearly points to a catalytic activity of serum albumin, it does not exclude an activity toward less-reactive substrates due to contamination of some HSA preparations. Indeed, the hypothesis of a contamination by plasma cholinesterase (EC 3.1.1.8) has been raised [126][127]. The efficient hydrolysis of nicotinate esters by HSA (see Chapt. 8) [128][129] could be due to contamination by cholinesterase in samples of a commercially available, essentially fatty acid free albumin. Support for this hypothesis was obtained when HSA contaminated with cholinesterase was resolved into two peaks by affinity chromatography, and the esterase activity toward nicotinate esters was found exclusively in the cholinesterase fraction [130],... 

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