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Acetylcholinesterases

Figure 10.1-12. Distribution of compounds in the layer of acetylcholinesterase inhibitors neurons colored m black and marked with a circle contain i inhibitors of acetylcholinesterase, and neurons in light gray contain other compounds. Figure 10.1-12. Distribution of compounds in the layer of acetylcholinesterase inhibitors neurons colored m black and marked with a circle contain i inhibitors of acetylcholinesterase, and neurons in light gray contain other compounds.
Enzyme-Catalyzed Reactions Enzymes are highly specific catalysts for biochemical reactions, with each enzyme showing a selectivity for a single reactant, or substrate. For example, acetylcholinesterase is an enzyme that catalyzes the decomposition of the neurotransmitter acetylcholine to choline and acetic acid. Many enzyme-substrate reactions follow a simple mechanism consisting of the initial formation of an enzyme-substrate complex, ES, which subsequently decomposes to form product, releasing the enzyme to react again. [Pg.636]

Mode of Action. All of the insecticidal carbamates are cholinergic, and poisoned insects and mammals exhibit violent convulsions and other neuromuscular disturbances. The insecticides are strong carbamylating inhibitors of acetylcholinesterase and may also have a direct action on the acetylcholine receptors because of their pronounced stmctural resemblance to acetylcholine. The overall mechanism for carbamate interaction with acetylcholinesterase is analogous to the normal three-step hydrolysis of acetylcholine however, is much slower than with the acetylated enzyme. [Pg.293]

Galanthamine (23) is an alkaloid extracted from the common snowdrop Galanthus nivalis. This compound is a long-acting, competitive AChE inhibitor which appears to be somewhat more specific for acetylcholinesterase than plasma butyrylcholinesterase (132). It is well tolerated during long-term treatment (133) and is being evaluated clinically for AD (134). [Pg.98]

Neurokinin effects are terrninated by proteolysis. In vitro acetylcholinesterase (ACE) and enkephalinase can hydrolyze substance P. However, there appears to be no clear evidence that either acetylcholinesterase or ACE limit the actions of released substance P. Enkephalinase inhibitors, eg, thiorphan, can augment substance P release or action in some systems but the distribution of enkephalinase in the brain does not precisely mirror that of substance P. There appears to be a substance P-selective enzyme in brain and spinal cord. [Pg.576]

One of the homochiral starting materials (45) for the acetylcholinesterase (ACE) inhibitor captopril [62571 -86-2] (47) is produced by a Hpase enzyme-catalyzed resolution of racemic 3-methyl-4-acetylthiobutyric acid (44) and L-proline (46) (65). [Pg.242]

Biological activities also may correlate with electronic substituent factors alone, eg, the inhibition of acetylcholinesterase by six diethyl phenyl phosphates (36) gave r = 0.95 for... [Pg.273]

The acetylcholinesterase inhibitor tacrine (64) was approved for the treatment of mild-to-moderate SDAT in the United States in 1993 followed by several other countries. The acetylcholinesterase inhibitor galanthamine (65), which has long been in clinical use in Austria for the treatment of indications such as facial neuralgia and residual poliomyelitis paralysis, has also been approved for use in... [Pg.238]

A two-site immunometric assay of undecapeptide substance P (SP) has been developed. This assay is based on the use of two different antibodies specifically directed against the N- and C-terminal parts of the peptide (95). Affinity-purified polyclonal antibodies raised against the six amino-terminal residues of the molecule were used as capture antibodies. A monoclonal antibody directed against the carboxy terminal part of substance P (SP), covalently coupled to the enzyme acetylcholinesterase, was used as the tracer antibody. The assay is very sensitive, having a detection limit close to 3 pg/mL. The assay is fiiUy specific for SP because cross-reactivity coefficients between 0.01% were observed with other tachykinins, SP derivatives, and SP fragments. The assay can be used to measure the SP content of rat brain extracts. [Pg.247]

In the body, metrifonate converts to the active metaboUte dichlorvos, (2,2-dichlorovinyl dimethyl phosphate), which is responsible for the inhibition of the enzyme acetylcholinesterase in the susceptible worm. This effect alone is unlikely to explain the antischistosomal properties of metrifonate (19). Clinically, metrifonate is effective only against infection caused by S. haematobium. Metrifonate is administered in three doses at 2-wk intervals (17). The dmg is well tolerated. Side effects such as mild vertigo, nausea, and cramps are dose-related. This product is not available in the United States. The only manufacturer of metrifonate is Bayer A.G. of Leverkusen, Germany. [Pg.244]

Diethyl 0-(3-methyl-5-pyrazolyl) phosphate (722) and 0,0-diethyl 0-(3-methyl-5-pyrazolyl) phosphorothioate (723) were prepared in 1956 by Geigy and they act, as do all organophosphates in both insects and mammals, by irreversible inhibition of acetylcholinesterase in the cholinergic synapses. Interaction of acetylcholine with the postsyn-aptic receptor is therefore greatly potentiated. 0-Ethyl-5-n-propyl-0-(l-substituted pyrazol-4-yl)(thiono)thiolphosphoric acid esters have been patented as pesticides (82USP4315008). [Pg.297]

An enzymatic assay can also be used for detecting anatoxin-a(s). " This toxin inhibits acetylcholinesterase, which can be measured by a colorimetric reaction, i.e. reaction of the acetyl group, liberated enzymatically from acetylcholine, with dithiobisnitrobenzoic acid. The assay is performed in microtitre plates, and the presence of toxin detected by a reduction in absorbance at 410 nm when read in a plate reader in kinetic mode over a 5 minute period. The assay is not specific for anatoxin-a(s) since it responds to other acetylcholinesterase inhibitors, e.g. organophosphoriis pesticides, and would need to be followed by confirmatory tests for the cyanobacterial toxin. [Pg.117]

Of the known cyanobacterial toxins only anatoxin-fl(s) is detected and is, therefore, able to be screened for by acetylcholinesterase inhibition. [Pg.121]

SJ Cho, ML Garsia, J Bier, A Tropsha. Stracture-based alignment and comparative molecular held analysis of acetylcholinesterase inhibitors. J Med Chem 39(26) 5064-5071, 1996. [Pg.367]

ACETYLCHOLINESTERASE INHIBITING PESTICIDES Cholinesterase activity in red Discretionary 70% of individuals Ns... [Pg.86]

FIGURE 5.46 Interaction of the serine hydroxyl residue in the catalytically active site of acetylcholinesterase enzyme with esters of organophosphates or carbamates. The interaction leads to binding of the chemical with the enzyme, inhibition of the enzyme, inhibition of acetylcholine hydrolysis, and thus accumulation of acetylcholine in the synapses. [Pg.287]

An adjacent tnfluoromethyl group sharply increases the electrophilic character of the carbonyl carbon Compounds that readily form hydrates and hemiacetals show a time-dependent reversible mhibition of the en yme acetylcholinesterase (equation 2), in which the tight complex makes inhibition only partially reversible [75] In comparison with a nonfluormated analogue, several aliphatic ketones flanked by CFj and CF2 groups, are exceptionally potent reversible inhibitors of acetylcholinesterase, as documented by companson of inhibition constants shown in equation 3 [16 ... [Pg.1012]

Acetylcholine (indirectly phosphororganic pesticides in the ng/ml-range) Acetylcholinesterase Choline, acetic acid physiol, salt solution pH 7.2 Acetylcholine-Liquid membrane 10 2 10 4 M... [Pg.255]

So far, many kinds of nucleophiles active for hydrolysis such as imidazolyl-, amino-, pyridino-, carboxyl- and thiol-groups, have been used for preparation of hydrolase models. Overberger et al.108,1091 prepared copolymers of vinylimidazole and acrylic acid 60 (PVIm AA), by which the cationic substrate, 61 (ANTI), was hydrolyzed. This kind of copolymer is considered to be a model of acetylcholinesterase. With ANTI, the rate of the copolymer catalysis was higher than that of imidazole itself in the higher values of pH, as is seen in Table 9. In this work, important contributions of the electrostatic interactions are clear. The activity of the copolymer was not as high with the negatively charged and neutral substrates. [Pg.162]

Acetylcholine serves as a neurotransmitter. Removal of acetylcholine within the time limits of the synaptic transmission is accomplished by acetylcholinesterase (AChE). The time required for hydrolysis of acetylcholine at the neuromuscular junction is less than a millisecond (turnover time is 150 ps) such that one molecule of AChE can hydrolyze 6 105 acetylcholine molecules per minute. The Km of AChE for acetylcholine is approximately 50-100 pM. AChE is one of the most efficient enzymes known. It works at a rate close to catalytic perfection where substrate diffusion becomes rate limiting. AChE is expressed in cholinergic neurons and muscle cells where it is found attached to the outer surface of the cell membrane. [Pg.12]

Acetylcholinesterase (EC 3.1.1.7) (AChE) Acetylcholine acetylhydrolase True ChE ChE I ChE Acet-ylthiocholinesterase Acetylcholine hydrolase Acetyl (3-methylcholinesterase Erythrocyte ChE Butyrylcholinesterase (EC 3.1.1.8) (BChE or BuChE) ChE Pseudocholinesterase Plasma ChE Acylcholine acylhydrolase Non-specific ChE ChEII Benzoylcholinesterase Propionylcholinesterase... [Pg.357]

The esteratic subsite contains the catalytic machinery of the enzyme. The catalytic triad residues - Ser 200, His 440 and Glu 327 (the residue numbering in this section refers to Torpedo californica acetylcholinesterase, TcAChE) - are identical in both enzymes and basically in the same positions. [Pg.358]


See other pages where Acetylcholinesterases is mentioned: [Pg.509]    [Pg.510]    [Pg.511]    [Pg.662]    [Pg.7]    [Pg.24]    [Pg.279]    [Pg.290]    [Pg.290]    [Pg.300]    [Pg.301]    [Pg.96]    [Pg.98]    [Pg.98]    [Pg.100]    [Pg.517]    [Pg.318]    [Pg.404]    [Pg.403]    [Pg.112]    [Pg.439]    [Pg.440]    [Pg.145]    [Pg.646]    [Pg.792]    [Pg.12]    [Pg.357]   
See also in sourсe #XX -- [ Pg.189 ]

See also in sourсe #XX -- [ Pg.130 ]




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Acetylcholine Acetylcholinesterase

Acetylcholine receptors Acetylcholinesterase

Acetylcholine, deactivation acetylcholinesterase

Acetylcholinesterase

Acetylcholinesterase

Acetylcholinesterase (AChE

Acetylcholinesterase (AChE true

Acetylcholinesterase (AChE true inhibition

Acetylcholinesterase (AchE Inhibitor

Acetylcholinesterase , virtual screening

Acetylcholinesterase ACHE gene

Acetylcholinesterase AChE reactivation

Acetylcholinesterase AChE-based biosensors

Acetylcholinesterase Adaptation

Acetylcholinesterase acceleration

Acetylcholinesterase acidic group

Acetylcholinesterase active site

Acetylcholinesterase active-site gorge

Acetylcholinesterase activity

Acetylcholinesterase activity assays

Acetylcholinesterase activity measurements

Acetylcholinesterase affinities

Acetylcholinesterase ageing

Acetylcholinesterase agents

Acetylcholinesterase alkaloid reversible inhibitor

Acetylcholinesterase amniotic fluid

Acetylcholinesterase anionic site

Acetylcholinesterase binding sites

Acetylcholinesterase biological role

Acetylcholinesterase bisquaternary

Acetylcholinesterase blood-brain barrier

Acetylcholinesterase carbamates

Acetylcholinesterase carbamylation

Acetylcholinesterase catalytic site

Acetylcholinesterase catalytic triad

Acetylcholinesterase choline

Acetylcholinesterase decreased

Acetylcholinesterase deficiency

Acetylcholinesterase distribution

Acetylcholinesterase donepezil

Acetylcholinesterase drug targets

Acetylcholinesterase drugs

Acetylcholinesterase enzyme inhibition

Acetylcholinesterase enzyme mechanism

Acetylcholinesterase enzyme reactor

Acetylcholinesterase erythrocyte

Acetylcholinesterase esteratic site

Acetylcholinesterase exposure-induced accumulation

Acetylcholinesterase fluoride

Acetylcholinesterase formation

Acetylcholinesterase forms

Acetylcholinesterase function

Acetylcholinesterase galantamine

Acetylcholinesterase gene

Acetylcholinesterase gene structure

Acetylcholinesterase genetic variants

Acetylcholinesterase histochemistry

Acetylcholinesterase hydrolysis

Acetylcholinesterase in skeletal muscle

Acetylcholinesterase induction

Acetylcholinesterase inhibition antidotes

Acetylcholinesterase inhibition by nerve agents

Acetylcholinesterase inhibition carbamates

Acetylcholinesterase inhibition clinical symptoms

Acetylcholinesterase inhibition individual agents

Acetylcholinesterase inhibition irreversible

Acetylcholinesterase inhibition kinetics

Acetylcholinesterase inhibition mechanisms

Acetylcholinesterase inhibition muscarinic effects

Acetylcholinesterase inhibition neurotoxicity

Acetylcholinesterase inhibition nicotinic effects

Acetylcholinesterase inhibition organophosphate nerve agents

Acetylcholinesterase inhibition oxime-induced

Acetylcholinesterase inhibition preventing

Acetylcholinesterase inhibition products

Acetylcholinesterase inhibition prolonged

Acetylcholinesterase inhibition spontaneous

Acetylcholinesterase inhibition structure-activity relationships

Acetylcholinesterase inhibition time course

Acetylcholinesterase inhibition tolerance

Acetylcholinesterase inhibition, reactivation

Acetylcholinesterase inhibitors

Acetylcholinesterase inhibitors AChEIs)

Acetylcholinesterase inhibitors Alzheimer disease dementia

Acetylcholinesterase inhibitors Organophosphates

Acetylcholinesterase inhibitors acute toxicity

Acetylcholinesterase inhibitors aging

Acetylcholinesterase inhibitors analogs

Acetylcholinesterase inhibitors analytical methods

Acetylcholinesterase inhibitors anatoxin

Acetylcholinesterase inhibitors antagonists

Acetylcholinesterase inhibitors antidotes

Acetylcholinesterase inhibitors behavioral effects

Acetylcholinesterase inhibitors bivalent

Acetylcholinesterase inhibitors cholinergic effects

Acetylcholinesterase inhibitors cholinesterase inhibition

Acetylcholinesterase inhibitors cholinesterase inhibitor donepezil

Acetylcholinesterase inhibitors design

Acetylcholinesterase inhibitors drug interactions

Acetylcholinesterase inhibitors for Alzheimer s disease

Acetylcholinesterase inhibitors huprines

Acetylcholinesterase inhibitors onchidal

Acetylcholinesterase inhibitors organophosphate nerve agents

Acetylcholinesterase inhibitors pharmacokinetics

Acetylcholinesterase inhibitors pharmacology

Acetylcholinesterase inhibitors physostigmine

Acetylcholinesterase inhibitors poisoning

Acetylcholinesterase inhibitors prevention/treatment

Acetylcholinesterase inhibitors properties

Acetylcholinesterase inhibitors side effects

Acetylcholinesterase inhibitors signs/symptoms

Acetylcholinesterase inhibitors substrates from acetylcholine

Acetylcholinesterase inhibitors therapy

Acetylcholinesterase inhibitors toxicity

Acetylcholinesterase inhibitors, effects

Acetylcholinesterase insecticidal

Acetylcholinesterase insecticides, poisoning with

Acetylcholinesterase irreversible

Acetylcholinesterase isoenzymes

Acetylcholinesterase knockout mice

Acetylcholinesterase localization

Acetylcholinesterase molecular forms

Acetylcholinesterase molecule

Acetylcholinesterase muscle-specific expression

Acetylcholinesterase nematode

Acetylcholinesterase nerve agent antidote

Acetylcholinesterase neuronal

Acetylcholinesterase neurotransmitter release

Acetylcholinesterase normal function

Acetylcholinesterase organic phosphates

Acetylcholinesterase organophosphate-binding

Acetylcholinesterase organophosphates inhibition

Acetylcholinesterase organophosphorus inhibitors

Acetylcholinesterase oxyanion hole

Acetylcholinesterase parasitic nematodes

Acetylcholinesterase pathway

Acetylcholinesterase peripheral

Acetylcholinesterase peripheral anionic site

Acetylcholinesterase pesticides detection

Acetylcholinesterase phosphorylated

Acetylcholinesterase phosphorylation

Acetylcholinesterase phosphylated

Acetylcholinesterase plant-derived

Acetylcholinesterase primary

Acetylcholinesterase properties

Acetylcholinesterase prophylaxis, soman

Acetylcholinesterase protective effects

Acetylcholinesterase pseudosubstrate

Acetylcholinesterase purification

Acetylcholinesterase quaternary

Acetylcholinesterase reaction

Acetylcholinesterase reactivation

Acetylcholinesterase reactivators

Acetylcholinesterase reactivators reactivation potency

Acetylcholinesterase receptor

Acetylcholinesterase receptor binding

Acetylcholinesterase regulation

Acetylcholinesterase reversible

Acetylcholinesterase reversible inhibitors

Acetylcholinesterase rivastigmine

Acetylcholinesterase sensor

Acetylcholinesterase serine residue

Acetylcholinesterase slow reactivation

Acetylcholinesterase sources

Acetylcholinesterase stability

Acetylcholinesterase stereoselectivity

Acetylcholinesterase structure

Acetylcholinesterase structure-activity relationship

Acetylcholinesterase substrate binding rates

Acetylcholinesterase substrate specificity

Acetylcholinesterase substrates

Acetylcholinesterase therapeutic applications

Acetylcholinesterase tissue distribution

Acetylcholinesterase toxicity

Acetylcholinesterase turnover number

Acetylcholinesterase using acetylthiocholine

Acetylcholinesterase variants

Acetylcholinesterase, activation volume

Acetylcholinesterase, comparative

Acetylcholinesterase, comparative inhibition

Acetylcholinesterase, inhibition

Acetylcholinesterase, inhibition acetylcholine

Acetylcholinesterase, inhibition catalysis

Acetylcholinesterase, inhibition reversible

Acetylcholinesterase, inhibition with phosphorylated

Acetylcholinesterase, phosphorylated esteratic

Acetylcholinesterase, serine function

Acetylcholinesterase, suicide

Acetylcholinesterase, suicide inhibitors

Acetylcholinesterase-inhibiting insecticides

Acetylcholinesterases classification

Acetylcholinesterases synergists

Acyl pocket, acetylcholinesterase

Acylation, acetylcholinesterase

Aging acetylcholinesterase

Aging nerve agent-acetylcholinesterase

Aging of acetylcholinesterase

Aging, phosphorylated acetylcholinesterase

Alkylphosphates, acetylcholinesterase

Alkylphosphates, acetylcholinesterase inhibition

Antagonists acetylcholinesterase

Anticholinesterases Acetylcholinesterase

Anticholinesterases acetylcholinesterase inhibition

Antidotes acetylcholinesterase reactivators

Apoptosis acetylcholinesterase

Aromatic gorge, acetylcholinesterase

Biomarkers acetylcholinesterase

Bioscavengers acetylcholinesterase

Biosensors acetylcholinesterase

Biosensors acetylcholinesterase inhibition

Blood cells acetylcholinesterase

Blood human, measuring acetylcholinesterase

Brain acetylcholinesterase

CGRP), acetylcholinesterase (AChE), somatostatin and tyrosine hydroxylase in Purkinje cells

Caenorhabditis elegans acetylcholinesterase

Carbamate compounds acetylcholinesterase inhibition

Central nervous system receptors, acetylcholinesterase

Central nervous system receptors, acetylcholinesterase inhibition

Chemical warfare, acetylcholinesterase

Chemical warfare, acetylcholinesterase inhibition

Cholinergic system Acetylcholinesterase inhibition

Cholinergic system acetylcholinesterase activity

Cholinesterases Acetylcholinesterase

Cholinesterases Acetylcholinesterase, erythrocyte

Cholinesterases acetylcholinesterase inhibition

Detection acetylcholinesterase

Diaphragm acetylcholinesterase activity

Disulfoton acetylcholinesterase inhibition

Drugs acetylcholinesterase inhibitors

Electric eel acetylcholinesterase

Enzymes acetylcholinesterase

Esterases acetylcholinesterase inhibition

Fasciculin, acetylcholinesterase

Fasciculin, acetylcholinesterase inhibition

Fear, acetylcholinesterase

Galanthamine acetylcholinesterase

Inhibition of acetylcholinesterase

Inhibition of acetylcholinesterase AChE)

Inhibitors of acetylcholinesterase

Insecticides acetylcholinesterase inhibitors

Insecticides, acetylcholinesterase

Insecticides, acetylcholinesterase inhibition

Isoflurophate acetylcholinesterase

Kinetic modeling, acetylcholinesterase

MS Assay Development for Acetylcholinesterase

Mouse acetylcholinesterase

Muscarinic receptors acetylcholinesterase inhibition

Muscle acetylcholinesterase expression

Muscle fasciculations, acetylcholinesterase

Mutations acetylcholinesterase

Myasthenia gravis acetylcholinesterase inhibitors

Nerve agents acetylcholinesterase inhibition

Nerve function acetylcholinesterase

Nervous system acetylcholinesterase inhibition

Neuromuscular junction acetylcholinesterase

Neuromuscular junction acetylcholinesterase inhibition

Nicotinic receptors, acetylcholinesterase inhibition

Nippostrongylus brasiliensis acetylcholinesterase

Ocular acetylcholinesterase

Organophosphate compounds acetylcholinesterase inhibition

Organophosphates acetylcholinesterase

Organophosphorus nerve agent acetylcholinesterase inhibition

Oximes acetylcholinesterase reactivation

Paralysis acetylcholinesterase inhibition

Parathion acetylcholinesterase inhibition

Pharmacodynamic modeling Acetylcholinesterase inhibition

Phosphorylated acetylcholinesterase reactivators

Physostigmine acetylcholinesterase inhibition

Physostigmine, acetylcholinesterase

Propidium, acetylcholinesterase

Pseudosubstrate of acetylcholinesterase

Reactivation Acetylcholinesterase reactivators

Reactivation potency, acetylcholinesterase

Reactivators, acetylcholinesterase molecule

Red blood cell acetylcholinesterase

Red cells acetylcholinesterase

Russian acetylcholinesterase inhibition

Serine active site acetylcholinesterase

Serine residue acetylcholinesterase active site

Serine-type acetylcholinesterase

Snake venom acetylcholinesterase

Status epilepticus acetylcholinesterase inhibitor-induced

Structure of acetylcholinesterase

Structure of the acetylcholinesterase enzyme

Synapse acetylcholinesterase inhibition

Terferol as acetylcholinesterase

The active site of acetylcholinesterase

Torpedo acetylcholinesterase

Torpedo californica, acetylcholinesterase

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