Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analogues of the potent inhibitor of choline acetyltransferase (CAT) (E)-4-(1-naphthylvinyl)pyridine methiodide were synthesized and evaluated for their ability to inhibit CAT and protect against nerve agent intoxication. Several compounds, notably (E)-1-(2-hydroxyethyl)-(1-naphthylvinyl)pyridinium bromide (3), (E)-1-methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine hydrochloride (22), and (E)-1-methyl-4-(1-naphthylvinyl)piperidine hydrochloride (23), were found to afford significant protection against sarin in the mouse and against soman in the guinea pig. However, protection was apparently not related to CAT inhibition. Compound 23, our most effective compound in protecting against nerve agent, was without CAT inhibitory activity. Compound 22, which proved to be a potent CAT inhibitor, most likely owed this activity to being dehydrogenated back to the pyridinium quaternary salt by oxidative enzymes. Several of the (naphthylvinyl)pyridine quaternary salts, but not their tertiary amine analogues, were found to be effective in slowing the rate of aging of soman-inhibited acetylcholinesterase. Ability to slow the rate of aging was enhanced by introduction of methoxy substituents on the aryl moiety whereas the aging rate was actually accelerated by chloro substituents. To date, our most effective compound in slowing the rate of aging, (E)-4-[(4-methoxy-1-naphthyl)vinyl]pyridine methochloride (6), did not provide significant protection against soman in the mouse.
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PMID:Approaches to protection against nerve agent poisoning. (Naphthylvinyl)pyridine derivatives as potential antidotes. 335 60

A 20 S asymmetric (non-globular) form of acetylcholinesterase (AChE, E.C. 3.1.1.7) has been purified from 1-day chick muscle. This form is a hybrid molecule containing both AChE and butyrylcholinesterase (BuChE, E.C. 3.1.1.8) catalytic subunits, linked through a collagenous tail. However, the 20 S hybrid AChE/BuChE could not account for the total enzyme activities of AChE and BuChE in a high-salt/Triton X-100 extract of 1-day chick muscle. By applying AChE- and BuChE-specific monoclonal antibodies for immunoadsorption, homogeneous asymmetric AChE and BuChE forms were also identified in that extract. The homogeneous BuChE accounts for 20% of the total activity of the asymmetric BuChE present and sediments at 17 S. About 6% of the asymmetric AChE present is, likewise, in a homogeneous, instead of the hybrid, form. The 17 S asymmetric BuChE does not react with monoclonal antibodies specific for the collagenous tail of the hybrid 20 S AChE/BuChE molecule, suggesting that the collagenous subunit differs between these two forms.
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PMID:Identification of a 17 S asymmetric butyrylcholinesterase in chick muscle by monoclonal antibodies. 336 25

Antibodies against acetylcholinesterase were found in the serum of a patient presenting dyspnea, generalized muscle paresis, diminished tendon reflexes, and fasciculations. Electrodiagnostic studies showed a decremental response, an incomplete interference pattern, and reduced motor nerve conduction velocity. Edrophonium administration resulted in extreme cholinergic crisis. Biopsies displayed muscle atrophy and nervous tissue degeneration. Recurrent acute respiratory failure ended in death. The patient's serum pseudocholinesterase and red blood cells acetylcholinesterase levels were generally very low, with periodical fluctuations. Minute quantities of the patient's serum inhibited the activity of cholinesterases from normal human serum and from various fetal tissues. Enzyme inhibition was abolished following preadsorption of the serum immunoglobulins with goat antihuman Fab, and radioiodinated acetylcholinesterase from human erythrocytes was precipitated by the patient's serum, confirming that anticholinesterase antibodies were present. Acetylcholinesterase extracted from fetal striated muscle with detergent and salt was inhibited to a larger extent than the enzymes similarly prepared from other fetal tissues and more efficiently than buffer-soluble muscle enzyme. These findings suggest that the patient's serum contained antibodies which interacted preferentially with the membrane-associated forms of muscle acetylcholinesterase and indicate that autoantibodies against acetylcholinesterase could play a role in the pathogenesis of the disease.
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PMID:Antibodies against acetylcholinesterase and low levels of cholinesterases in a patient with an atypical neuromuscular disorder. 339 Sep 68

We report an analysis of the solubility and hydrophobic properties of the globular forms of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) from various Torpedo tissues. We distinguish globular nonamphiphilic forms (Gna) from globular amphiphilic forms (Ga). The Ga forms bind micelles of detergent, as indicated by the following properties. They are converted by mild proteolysis into nonamphiphilic derivatives. Their Stokes radius in the presence of Triton X-100 is approximately 2 nm greater than that of their lytic derivatives. The G2a forms fall in two classes. Class I contains molecules that aggregate in the absence of detergent, when mixed with an AChE-depleted Triton X-100 extract from electric organ. AChE G2a forms from electric organs, nerves, skeletal muscle, and erythrocyte membranes correspond to this type, which is also detectable in detergent-soluble (DS) extracts of electric lobes and spinal cord. Class II forms never aggregate but only present a slight shift in sedimentation coefficient, in the presence or absence of detergent. This class contains the AChE G2a forms of plasma and of the low-salt-soluble (LSS) fractions from spinal cord and electric lobes. The heart possesses a BuChE G2a form of class II in LSS extracts, as well as a similar G1a form. G4a forms of AChE, which are solubilized only in the presence of detergent and aggregate in the absence of detergent, represent a large proportion of cholinesterase in DS extracts of nerves and spinal cord, together with a smaller component of G4a BuChE. These forms may be converted to nonamphiphilic derivatives by Pronase. Nonaggregating G4a forms exist at low levels in the plasma (BuChE) and in LSS extracts of nerves (BuChE) and spinal cord (AChE).
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PMID:Amphiphilic and nonamphiphilic forms of Torpedo cholinesterases: I. Solubility and aggregation properties. 341 26

One form of acetylcholinesterase (AChE), 3S, has been identified in the thymus of normal mice as the predominant species. Histochemical studies show that the AChE is localized to nerves or to nerve-related tissues. The form isolated is composed of a salt and a detergent-sensitive fraction. Since the sedimentation values and the kinetics of the two fractions are identical, it is proposed that only one gene encodes for this globular 3S species of AChE.
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PMID:Nerve-related 3S acetylcholinesterase in murine thymus. 347 74

A hybrid cell line (E-2) that secretes the enzyme acetylcholinesterase (AChE) has been prepared. The E-2 cell was the product of a fusion between primary mouse hepatocytes and a chemically transformed rat liver cell line (FRL), neither of which expresses AChE activity. The enzyme was determined to be AChE on the basis of its susceptibility to inhibition by BW284c51 but not by iso-OMPA, as well as its substrate specificity. Although the secreted enzyme was salt soluble and its activity not modified by the addition of the nonionic detergent, Triton X-100, the activity of the cellular enzyme (derived from homogenates of E-2 cells) was greatly enhanced in the presence of the detergent.
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PMID:Secretion of acetylcholinesterase by a mouse hepatocyte X rat liver cell hybrid culture. 349 Oct 63

A significant proportion of the acetylcholinesterase that is present in the electric organ of Torpedo californica exists as a presynaptic membrane molecule. The monoclonal antibody Tor 23 binds the Torpedo presynaptic nerve membrane where it recognizes a polypeptide of 68,000 daltons. Our present studies indicate that Tor 23 identifies acetylcholinesterase. From the homogenates of Torpedo nerve terminals, Tor 23 immunoprecipitates measurable esterase activity. Esterase precipitation was not observed with no Tor 23 added; nor was it observed with any other test antibodies, including other Tor antibodies, in particular, Tor 70, which binds, as does Tor 23, to the presynaptic nerve membrane. The esterase activity was specific for acetylcholinesterase. Our studies indicate the molecule defined by Tor 23 has the solubility properties described for that of presynaptic acetylcholinesterase: it is soluble in detergent-treated electroplax homogenates and insoluble in high-salt extractions. In sections of Torpedo back muscle, both nerve and endplate acetylcholinesterase can be detected histochemically. Tor 23 localizes to the nerve and is not clustered at the endplate. The utility of the antibody Tor 23 thus includes biochemical and histological analyses of the multiple forms of acetylcholinesterase.
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PMID:Monoclonal antibody Tor 23 recognizes a determinant of a presynaptic acetylcholinesterase. 355 31

The embryonic development of total specific activities as well as of molecular forms of acetylcholinesterase (AChE, EC 3.1.1.7) and of butyrylcholinesterase (BChE, EC 3.1.1.8) have been studied in the chick brain. A comparison of the development in different brain parts shows that cholinesterases first develop in diencephalon, then in tectum and telencephalon; cholinesterase development in retina is delayed by about 2-3 days; and the development in rhombencephalon [not studied until embryonic day 6 (E6)] and cerebellum is last. Both enzymes show complex and independent developmental patterns. During the early period (E3-E7) first BChE expresses high specific activities that decline rapidly, but in contrast AChE increases more or less constantly with a short temporal delay. Thereafter the developmental courses approach a late phase (E14-E20), during which AChE reaches very high specific activities and BChE follows at much lower but about parallel levels. By extraction of tissues from brain and retina in high salt plus 1% Triton X-100, we find that both cholinesterases are present in two major molecular forms, AChE sedimenting at 5.9S and 11.6S (corresponding to G2 and G4 globular forms) and BChE at 2.9S and 10.3S (G1 and G4, globular). During development there is a continuous increase of G4 over G2 AChE, the G4 form reaching 80% in brain but only 30% in retina. The proportion of G1 BChE in brain remains almost constant at 55%, but in retina there is a drastic shift from 65% G1 before E5 to 70% G4 form at E7.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitative development and molecular forms of acetyl- and butyrylcholinesterase during morphogenesis and synaptogenesis of chick brain and retina. 358 28

Acetylcholinesterase was solubilized from rabbit white muscle by means of dilute buffer and Triton X-100 (0.5%). About 50% of total activity was brought into solution with buffer, the rest being solubilized by extracting the tissue with buffer and Triton X-100. The enzyme activity recovered in the supernatants was 170% of that found in the homogenate in the absence of Triton X-100 indicating that, to some extent, the enzyme could be found in an occluded form in muscle. At suboptimum substrate concentration the Triton-solubilized acetylcholinesterase displayed a negative cooperativity, this phenomenon being greatly modified in the presence of NaCl. As the salt concentration increased (0-400 mM) the enzyme activity decreased, the Km values being linearly-dependent on the NaCl concentration in the assay medium. We propose a kinetic pattern to explain both the negative cooperativity produced by the substrate and the effect of NaCl on the kinetic behaviour on this enzyme. Our data are consistent with the hypothesis of binding of substrate to both the catalytic anionic site and a peripheral anionic site, the salt showing the capacity to compete with the substrate for these two binding sites.
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PMID:Influence of NaCl on the kinetic behaviour of mammalian muscle acetylcholinesterase. 359 83

Proteolytic fragmentation of [3H]diisopropylfluorophosphate-labelled catalytic subunits of different molecular forms of acetylcholinesterase demonstrates that all forms extracted from the electric organ from Torpedo marmorata are true acetylcholinesterases. This is supported by immunochemical results showing that the radiolabelled polypeptides are readily recognized by specific anti-acetylcholinesterase antibodies. Although distinct structural differences exist, all forms contain a similar peptide carrying the serine hydroxyl of the esteratic subsite. Dimeric, detergent-soluble acetylcholinesterase is present in the low-salt-soluble extract (Mr of the catalytic subunit 66,000) together with a monomeric form (apparent Mr 76,000). This monomeric polypeptide is hydrophilic, enzymatically inactive, and might represent a precursor of the asymmetric forms of acetylcholinesterase.
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PMID:Inactive monomeric acetylcholinesterase in the low-salt-soluble extract of the electric organ from Torpedo marmorata. 359 80


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