Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the first 4 postnatal days, the atrioventricular specialized tissue of the rat contains butyrylcholinesterase alone. The next 7 days are associated with a mixture of both acetyl and butyryl activity, but after the 12th day, acetylcholinesterase is found to predominate largely. It is suggested that this change in activity is related to the growth of adrenergic nerves into the heart on the 4th day. Administration of antinerve growth factor prevents the development of these nerves and is found to delay the onset of the change in cholinesterase activity from butyryl to acetyl from the 5th day until the 21st. Only after the 31st day is acetylcholinesterase the most prominent enzyme in treated animals.
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PMID:The relationship between innervation and the cholinesterases of the rat atrioventricular node. 83 22

As a continuation of our efforts to develop and study inhibitors which act presynaptically on neuromuscular function, sulfur analogues of hemicholinium-3 (HC-3, 1) and acetyl-seco-hemicholinium-3 (AcHC-3, 3) were prepared. In each case sulfur is substituted for the noncarbonyl oxygen in HC-3 (1) and AcHC-3 (3). As expected on the basis of conformational differences between acetylcholine and acetylthiocholine both of the thio analogues are produced in the seco form and do not cyclize spontaneously or when subjected to aqueous, acidic conditions up to 100 degrees C. Both compounds are stable in aqueous pH 7.4 solutions at 37 degrees C and in slightly acidic D2O solutions for more than 24 h. While thio-seco-hemicholinium 3 (11) is stable in the presence of acetylcholinesterase and butyrylcholinesterase in H2O at pH 7.4, acetylthio-seco-hemicholinium-3 (12) reacts within seconds to form the hemiacetal form of thiohemicholinium-3 (16). Mouse toxicity studies (LD50) indicate that while 12 is approximately as toxic as HC-3 (1) and AcHC-3 (3), 11 is 226 times less toxic. As in the studies with 1 and 3, mice were protected from 11 by choline and slightly by neostigmine. It is of interest, however, that almost equal and intermediate protection against 12 was afforded by choline and neostigmine. Structure-toxicity relationships of 1,3,11, 12, and 16 are discussed.
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PMID:Effect of sulfur substitution for the noncarbonyl oxygen in hemicholinium-3 and acetyl-seco-hemicholinium-3. Synthesis, biological activity, and structure-toxicity relationships. 83 27

Acetylcholinesterase (AChE) activity has been studied in normal, control and denervated muscle of rabbits by electron microscopic-cytochemistry and radiometric assay. A small amount of butyrylcholinesterase (BuChE) activity is also found in biochemical assay of unfixed muscle, but it is not demonstrable cytochemically in fixed specimens by the method used in this study. Both a soluble and particulate AChE activity are present in all specimens examined. The particulate activity is probably due to enzyme localized in the sarcotubular system and at the motor end-plate. Soluble AChE activity may represent those sites exhibiting random cytochemical end product, such as some areas of normal and denervated muscle and muscle nuclei, Schwann cells, and AChE-containing mononuclear cells in the connective tissue. There is a greater proportion of particulate than soluble AChE activity in normal and control muscle, a finding which is compatible with the well localized cytochemical sites. Four to six weeks post-denervation, there is a marked increase in extrajunctional AChE activity to peak values 15 to 30 fold above control values. The increase is accompanied by a reversal in the proportion of particulate to soluble enzyme, so that there is almost twice as much soluble as particulate AChE. There are also numerous "spots" of random cytochemical end product throughout extrajunctional muscle. The increase in levels of AChE activity, the change to predominantly soluble form, and the large numbers of new cytochemically active sites indicate that synthesis of new enzyme has taken place. Changes in AChE activity in denervated rabbit have been compared to those occurring in dystrophic mouse muscle. It has been suggested that there might be a relationship between the formation of new extrajunctional sarcoplasmic sites of AChE activity and the spread of alpha-bungarotoxin binding sites and chemosensitivity in developing and denervated muscle.
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PMID:Electron microscopic-cytochemical and biochemical studies of acetylcholinesterase activity in denervated muscle of rabbits. 83 40

In the cerebellum of four species belonging to the three main reptilian orders the histochemical localization of cholinesterases has been studied. The use of different substrate-inhibitor combinations permits to record the distribution patterns of acetylcholinesterase and pseudocholinesterase, mainly revealed as butyrylcholinesterase activity. From the neurological point of view it is interesting to note that acetylcholinesterase activity shows three different distribution patterns in reptilian cerebellum, thus confirming the characteristic variability previously noticed in the cerebellar cortex of other vertebrates.
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PMID:Cholinesterase patterns in the cerebellum of reptiles. 84 59

A series of halomethylated derivatives of dihydrocoumarins has been found to inhibit irreversibly proteases and esterases. alpha-Chymotrypsin, subtilish, elastase are rapidly inactivated in the presence of these compounds, while trypsin, kallicrein, papain are inhibited more slowly. Esterases like acetylcholinesterase and butyrylcholinesterase also lose activity in their presence. Two structural features of these inactivators are essential for inhibition: a reactive cis-ester function and an alkylating function. Analogues of these derivatives having only one of these characteristics are inefficient. Therefore it is suggested that the efficiency of these bifunctional reagents is due to their character of potential "suicide substrates".
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PMID:Inactivation of proteases and esterases by halomethylated derivatives of dihydrocoumarins. 88 30

Partition coefficients of a series of 2-substituted 3-(N,N-dimethyl)carbamyloxypyridines were determined in an octanol-buffer (pH 7.4) system. The values obtained were compared with the ihnibitory potencies of acetylcholinesterase and butyrylcholinesterase. No significant difference was found for the role of hydrophobicity in the two enzyme systems.
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PMID:Partition coefficients of selected pyridine carbamates and comparisons with their acetylcholinesterase and butyrylcholinesterase inhibitory potencies. 93 79

The distribution and postnatal variation of cholinesterase (ChE) activity were studied in 25 human and 25 dog hearts. The observed distribution pattern is remarkably constant, In dog hearts, the pattern is as follows: sinus node (SN) greater than left atrium (LA) greater than right atrium (RA) greater than right ventricle (RV) congruent to left ventricle (LV). The average acetylcholinesterase (AcChE) activities as expressed in international units per g wet tissue are: 1.66 (SN), 1.14 (LA), 0.70 (RA), 0.22 (RV), and 0.21 (LV). In human hearts, the AcChE distribution follows the pattern of RA greater than LA greater than RV congruent to LV with corresponding average activities of 1.70, 1.38, 0.51, and 0.44 IU. The postnatal variation of ChE activity is most pronounced in the RS of the heart in both species. The average AcChE activity in the RA of the newborn puppies is 0.51 IU as compared with 2.27 IU in newborn infants. In the adult heart, however, the average atrial AcChE activity is nearly identical (1.02 IU) in both species. An additional difference is the large (34-64%) contribution of butyrylcholinesterase (BuChE) to the total activity in dog hearts whereas the contribution of BuChE is small (7-15%) in human hearts.
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PMID:Studies on the distribution of cholinesterases: activity in the human and dog heart. 94 Jul 2

Acetylcholinesterase (AchE) and butyrylcholinesterase (BuchE) activities were studied in 20,000 g supernatant (S) and pellet (P) fractions of cerebrum1, caudate nucleus and cerebellum regions of human brain between the gestational ages of 20 and 40 weeks. On a per gram wet tissue basis, cerebrum and cerebellum had 60% and caudate nucleus had 80% of AchE activity present at 20-22 weeks as compared to 38-40 weeks of gestation. Specific activity (SA) of AchE did not change appreciably with gestational age in any of the P fractions. In S fractions of cerebrum and cerebullum there was about a 1.5-fold increase during this period. BuchE SA and activity per gram tissue in P and S fractions of cerebrum and cerebellum increased by 1.5- to 3-fold and decreased by about the same order of magnitude in caudate nucleus, during 20-40 weeks of gestation.
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PMID:Acetylcholinesterase and butyrylcholinesterase of developing human brain. 94 63

Multiple linear regression-analysis of variance was used to define relationships between final visual acuity and several parameters in 31 patients with reattached primary rhegmatogenous retinal detachments. Older patient age, preoperative macular detachment, clinically visible macular lesions, greater detachment duration and extent, and higher subretinal fluid butyrylcholinesterase activity were all inversely related to final acuity. The relationship of each parameter to final acuity, in conjunction with and apart from all the other parameters, was defined. Collectively the parameters accounted for 85% of the variation about the mean of the clinically observed finally acuities. The parameters could be weighted to give a generally, reasonably accurate prediction of final acuity at the time of surgery. The findings are consistent with a pathophysiological sequence involving alterations in the choroidal circulation and the blood-ocular barrier of the posterior segment.
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PMID:Prognosis of primary rhegmatogenous retinal detachments. 2. Accounting for and predicting final visual acuity in surgically reattached cases. 94 62

In order to develop and study inhibitors of neuromuscular function which act presynaptically, three stable analogues of acetyl-seco-hemicholinum-3 (AcHC-3,2) were prepared. These analogues have 2-ethoxyethyltrimethylammonium, 4-oxopentyltrimethylammonium, and n-pentyltrimethylammonium moieties substituted for the 2-acetylethyltrimethylammonium (acetylcholine) moieties of AcHC-3 (2) to form the ether 2, ketone 4, and alkane 5 analoggues of AcHC-3 (2). Although AcHC-3 (2) has been shown to undergo deesterification rapidly in basic solutions and slowly at pH 7.4, it has been found to be stable in H2O or D2O under slightly acidic conditions. All of the analogues are stable for extended time under both slightly acidic conditions and at pH 7.4 in H2O or D3O. It has been found that 2 reacts with acetylcholinesterase and butyrylcholinesterase within seconds in H2O at pH7.4. However, deesterification of 2 with subsequent cyclization to the hemiacetal form of hemicholinium-3 (HC-3, 1) is prevented at pH 7.4, possibly by an irreversible binding of 2 to the enzyme. The analogues 3-5, however, do not react under identical conditions. Mouse toxicity studies (LD50) indicate that 2 is approximately as toxic as HC-3 (1), whereas 3, 4, and 5 are 14.2, 23.8, and 43.1 times less toxic, respectively. The toxic effects of 3-5, like 1 and 2, are antagonized by choline but not by neostigmine in mice. Structure-activity relationships of 2-5 are discussed.
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PMID:Synthesis and structure-toxicity relationships of three new stable analogues of acetyl-seco-hemicholinium-3. 95 Jun 41


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