Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The anti-inflammatory activity of FL 70, a derivative of 2,5-dihydroxy-benzoic acid, was examined in a number of conventional experimental models. In addition, FL-70 was tested for its inhibitory action on enzymes. The results were as follows: 1. The induction of a local inflammatory reaction and the subsequent i.v. injection of trypan blue showed that FL 70 reduces the capillary permeability. 2, FL-70 significantly suppresses exudation in the formalin-induced peritonitis of the rat. 3. A slight inhibition of an edema in the footpad of the rat induced by formalin-dextran was not shown to be statistically significant. 4. Local swelling could be markedly inhibited in the turpentine-oil induced inflammatory reaction of the rabbit. 5. Exudation and formation of granulomatous tissue was inhibited in Selye's granuloma. 6. FL-70 markedly inhibited the local inflammatory reaction accompanying the cutaneous reaction in experimental vaccinia infection of the rabbit skin. The size of the infiltration after intracutaneous infection of the virus was not reduced. 7. FL-70 could not prevent the onset of clinical signs, if administered in experimental allergic encephalitis. 8. The activity of acid phosphatase was inhibited by FL-70. Alcaline phosphatase, cholinesterase, leucin aminopeptidase, glucose-6- phosphatase-dehydrogenase (G-6-PDH), trypsin and chymotrypsin were unaffe-ted. FL-70 inhibits the following, G-6-PDH activated reduction process: glucose-6-phosphate (see article).
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PMID:[Anti-inflammatory activity of a new quinoid polyradical (FL-70)]. 16 92

Light microscopic observations using Nomarski optics on the aldehyde-fixed hypothalamus of normal adult cats, monkeys and rabbits revealed the presence of cells in the supraoptic, paraventricular and periventricular nuclei which possessed yellow birefringent inclusions. Immunogold labelling showed that in each species the cells displayed oxytocin-like immunoreactivity, both in electron-dense inclusions within some (but not all) cisterns of rough endoplasmic reticulum and in secretory granules. The cells in cats and rabbits were in all respects indistinguishable from the homologous 'birefringent' cells previously described in rats, but in monkeys, cells frequently contained additional inclusions in cisterns of rough endoplasmic reticulum which did not display oxytocin or vasopressin-like immunoreactivity, even after trypsin, pepsin or chymotrypsin treatment of sections. Observations on cats and rabbits using fluorescence microscopy revealed that the birefringent cells possessed bright autofluorescence which facilitated the identification of more cells than were seen using Nomarski optics alone. Autofluorescence was abolished when sections were mounted in glycerol, or when exposed to light for protracted periods of time. Attempts to label for monoamines in these cells were not successful, suggesting that the fluorescence is not due to aldehyde-induced amine fluorescence. It is not clear why neuropeptides are retained in some rough endoplasmic reticulum cisterns. It is possible that these birefringent cells contain a peptide, or peptides, which are abnormal in some manner, or which may be other members of the oxytocin gene family. Alternatively, the processing of neuropeptides to permit their export to the Golgi apparatus may be deficient. Acetylcholinesterase (AChE) histochemistry revealed that, unlike other oxytocin neurons, cells with intracellular accretions lacked detectable acetyl cholinesterase. As AChE is a known peptidase, it may be involved in regulating peptide export from the rough endoplasmic reticulum.
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PMID:Neuropeptide accretions in the endoplasmic reticulum of oxytocinergic neurons in cats, monkeys and rabbits: a widespread phenomenon. 129 66

A series of trifluoromethyl ketones that reversibly inhibit acetylcholinesterase and pseudocholinesterase were synthesized. By analogy to chymotrypsin and on the basis of data reported here, we propose that the active-site serine adds to the ketone to form an ionized hemiketal. The compound (5,5,5-trifluoro-4-oxopentyl)trimethylammonium bicarbonate (1) inhibits acetylcholinesterase with Ki = 0.06 X 10(-9)M and pseudocholinesterase with Ki = 70 X 10(-9)M. Replacement of the nitrogen of 1 by carbon (compound 2) increases Ki for 1 200-fold for acetylcholinesterase but does not significantly alter Ki for pseudocholinesterase. The Ki for the methyl ketone corresponding to 2 is 2 X 10(-4)M for both enzymes, as compared with 12 X 10(-9)M for the trifluoromethyl ketone (acetylcholinesterase). For both enzymes, a linear decrease in log Ki with decreasing pK of the inhibitor hydrate was observed with ketones containing from 0 to 3 fluorines. We attribute this effect to the stabilization of the hemiketal oxyanion. The reduction of the pK of the hemiketal by the trifluoromethyl group is an important contributing factor to the low Ki of trifluoromethyl ketones. The inhibition of acetylcholinesterase by tetramethylammonium chloride and trifluoroacetone was compared to the inhibition by 1, which is a composite of the two smaller inhibitors. The entropic advantage of combining the smaller inhibitors into one molecule is 1.1 X 10(3)M. Inhibitors with Ki less than or equal to 70 X 10(-9) M are slow binding (Morrison, 1982; Morrison & Walsh, 1988). The kinetic data do not require formation of a noncovalent complex prior to formation of the ketal, although such a complex(es) cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition kinetics of acetylcholinesterase with fluoromethyl ketones. 260 96

Benzoyl- and isopentenoyl phosphoric triamides (BPA and IPA) strongly inhibited urease activities from jack bean, soybean, watermelon seed, Proteus mirabilis, P. rettgeri, P. vulgaris, Mycobacterium smegmatis, and Ureaplasma urealyticum. Their I50 values (the final concentration causing 50% inhibition), independent of enzyme source, were 2-21 nM, which are about 1,000-fold lower than that of caprylohydroxamic acid, one of the most potent urease inhibitors. ATP-urea amidolyase activity was inhibited 50% by BPA at a higher concentration of 0.28 mM, but was not affected by IPA even at 1.3 mM. Thirteen kinds of hydrolases (trypsin, chymotrypsin, thermolysin, leucine aminopeptidase, papain, lipase, alpha-amylase, glucuronidase, asparaginase, arylsulfatase, alkaline phosphatase, acid phosphatase, and true cholinesterase), two oxidoreductases (catalase and alcohol dehydrogenase), three transferases (glutamic-oxaloacetic aminotransferase, gamma-glutamyl transpeptidase, and arylsulfotransferase) and two kinases (pyruvate kinase and creatine kinase) were not affected at all even at 1 mM BPA and IPA. Exceptionally, pseudo-cholinesterase from human serum was inhibited by BPA and IPA, whose I50 values were 70 nM and 10 muM, respectively, using acetylthiocholine as a substrate. These values increased to 0.55 muM and 54 muM, respectively, when acetylcholine was used as a substrate. These results show that N-acylphosphoric triamides potently and specifically inhibit urease activity at concentrations of nM order.
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PMID:Specific inhibition of urease by N-acylphosphoric triamides. 384 42

1. The action of beryllium on the following enzymes has been examined: alkaline phosphatase (Escherichia coli and kidney), acid phosphatase, phosphoprotein phosphatase, apyrase (potato), adenosine triphosphatase (liver nuclei, liver mitochondria, brain microsomes), glucose 6-phosphatase, polysaccharide phosphorylases a and b, phosphoglucomutase, hexokinase, phosphoglyceromutase, ribonuclease, A-esterase (rabbit serum), cholinesterase (horse serum), chymotrypsin. Alkaline phosphatase and phosphoglucomutase are inhibited by 1mum-beryllium sulphate whereas the other enzymes are largely unaffected by 1mm-beryllium sulphate. 2. Possible mechanisms for the inhibition of phosphoglucomutase and alkaline phosphatase are discussed.
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PMID:The inhibition of enzymes by beryllium. 428 87

The interaction of serine protease (esterases) with 6-chloro-2-pyrones was investigated. Time-dependent inactivation of chymotrypsin, alpha-lytic protease, pig liver elastase, and cholinesterase was found with 3- and 5-benzyl-6-chloro-2-pyrone, as well as 3- and 5-methyl-6-chloro-2-pyrone. No inactivation was observed with the unsubstituted 6-chloro-2-pyrone. The substituted pyrones did not inactivate papain or carboxypeptidase A, as well as a number of other nonproteolytic enzymes. The substituted chloropyrones, therefore, show considerable selectivity toward serine proteases. Analogues in which the 6-chloro substituent is replaced by H or OH do not inactivate. The presence of the halogen is, therefore, essential for inactivation. Chymotrypsin catalyzes the hydrolysis of 3-benzyl-6-chloro-2-pyrone. At pH 7.5, (E)-4-benzyl-2-pentenedioic acid is the major product, and 2-benzyl-2-pentenedioic anhydride is a minor product. The ration of hydrolysis product found to the number of enzyme molecules inactivated varies from 14 to 40. The enzyme inactivated with the 3-benzyl compound does not show a spectrum characteristic of the pyrone ring. This suggests that inactivation by 3-benzyl-6-chloro-2-pyrone occurs in a mechanism-based fashion after enzymatic lactone hydrolysis. When the enzyme is inactivated with the 5-benzyl compound, absorbance due to the pyrone ring is observed. We suggest that inactivation occurs through an active site directed mechanism involving a 1,6-conjugate addition of an active site nucleophile to the pyrone ring.
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PMID:Novel inactivators of serine proteases based on 6-chloro-2-pyrone. 641 Nov 20

The pathology and enzymology of the intestinal mucosae of lambs dosed daily with 2500 Trichostrongylus vitrinus larvae and killed at five, nine or 14 weeks were compared with worm-free animals. The proximal small intestines of the infected lambs exhibited extensive mucosal damage at five and nine weeks, but only isolated lesions were found at 14 weeks. Activities of the brush border enzymes alkaline phosphatase, leucine amino-peptidase, maltase and glycyl-L-leucine dipeptidase were all significantly depleted during infection, although the magnitude, time of onset and duration of the individual enzyme responses varied. Mucosal activities of the pancreatic enzymes, trypsin and to a lesser extent chymotrypsin were also markedly decreased particularly during the first nine weeks of infection. Specific acetylcholinesterase activity was significantly increased throughout the study, maximal levels being observed at five weeks. In contrast 'pseudo'-cholinesterase levels were consistently within the control range. During the early stages of infection (five weeks) glutamine-oxaloacetate transaminase activity was significantly decreased, while aldolase and creatine phosphokinase levels were significantly elevated. At nine weeks low glutamine-oxaloacetate transaminase activities were again detected and lactate dehydrogenase activity was also markedly reduced. At 14 weeks the mean activities of all four enzymes were within the normal range as were superoxide dismutase levels throughout. Significant correlations were found between alkaline phosphatase, trypsin, chymotrypsin, aldolase and glutamine-oxaloacetate transaminase activities and the degree of mucosal damage within the individual lambs.
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PMID:Changes in the intestinal enzyme activity of lambs during chronic infection with Trichostrongylus vitrinus. 710 Jun 47

A simple direct spectrophotometric method for the determination of butyrylcholinesterase (EC 3.1.1.8) and arylesterase (EC 3.1.1.2) activities has been developed. New chromogenic substrates, (3-carboxypropyl)trimethylammonium iodide o-nitrophenyl ester (I) and (3-carboxypropyl)trimethylammonium iodide p-nitrophenyl ester (II), as well as new fluorogenic substrate, (3-carboxypropyl)trimethylammonium iodide 4'-methylumbelliferyl ester (III), were used in this study. Horse serum butyrylcholinesterase equally catalyzed hydrolysis of the compounds, I, II and III. Hydrolysis of these compounds by trypsin, chymotrypsin, acetylcholinesterase and carboxylesterase was negligible or quite slow. By human serum butyrylcholinesterase, however, only the compound I was preferentially hydrolyzed. The compound III, by contrast, was found to be a specific substrate for arylesterase of human serum without being affected by the butyrylcholinesterase. All these measurements were carried out readily and efficiently, by analyzing highly colored products with I and II, and highly fluorescent product with III.
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PMID:New chromogenic and fluorogenic substrates for the determination of butyrylcholinesterase and arylesterase activities. 720 43

31P NMR spectroscopy of butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and chymotrypsin (Cht) inhibited by pinacolyl methylphosphonofluoridate (soman), methylphosphonodifluoridate (MPDF), and diisopropyl phosphorofluoridate (DFP) allowed direct observation of the OP-linked moiety of aged (nonreactivatable) and nonaged organophosphorus (OP)-ChE conjugates. The 31P NMR chemical shifts of OP-ChE conjugates clearly demonstrated insertion of a P-O- bond into the active site of aged OP-ChE adducts. The OP moiety of nonaged OP-ChEs was shown to be uncharged. The OP-bound pinacolyl moiety of soman-inhibited and aged AChE was detached completely, whereas only partial dealkylation of the pinacolyl group was observed for soman-inhibited BChEs. This suggests that the latter enzyme reacted with the less active stereoisomer(s) of soman. In the case of soman-inhibited Cht, no dealkylation could be experimentally detected for any of the four stereoisomers of OP-Cht adducts. Results are consistent with the contention that the phenomenon of enzyme-catalyzed dealkylation of OP adducts of serine hydrolases strongly depends on the orientation of both the catalytic His and the carboxyl side chain of either Glu or Asp positioned next to the catalytic Ser. The denatured protein of aged OP-ChE or OP-Cht is a convenient leaving group in nucleophilic displacements of tetrahedral OP compounds despite the presence of a P-O- bond. This indicates that the unusual resistance to reactivation of the aged enzyme cannot be ascribed to simple electrostatic repulsion of an approaching nucleophile. The broadening of the 31P NMR signal of native OP-ChEs relative to that of OP-Cht is in agreement with the crystal structure of AChE, showing that the active site region of ChEs in solution resides in a deep, narrow gorge.
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PMID:Direct observation and elucidation of the structures of aged and nonaged phosphorylated cholinesterases by 31P NMR spectroscopy. 825 80

The disulfide bonds and N-glycosylation sites in a glycoprotein from the Rathke's gland secretion of the Kemp's ridley turtle (Lepidochelys kempi) have been characterized with respect to peptide sequences and glycan structures. The glycoprotein constitutes about 70% of the total protein in the secretion, and based on partial sequence information, it shows more than 20% identity with both the catalytic (esterases) and the noncatalytic (thyroglobulin) members of the esterase/lipase family of proteins. For the determination of the disulfide locations, the glycoprotein was digested with chymotrypsin, and the three HPLC peptide peaks yielding fluorescent products after treatment with tributylphosphine (Bu3P) and 4-(aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (ABD-F) were collected. The three fractions were treated with the same reagents in separate experiments, the resulting pairs of ABD-Cys-containing peptides were separated by HPLC, and the sequence of each individual peptide was determined. The peptide identity established that three disulfide bonds existed in the glycoprotein: Cys 65-Cys 91, Cys 254-Cys 265, and Cys 130-Cys 404; the first two of these are conserved in all the members of the esterase family. For the study of the glycosylation sites, the glycoprotein was reduced with Bu3P and the SH groups covalently blocked with ABD-F, and the resulting product was digested with chymotrypsin. The glycopeptides were isolated by affinity chromatography, separated by reverse-phase HPLC, and subjected to sequence analysis and fast atom bombardment mass spectrometry before and after separation of the glycans and the peptides through the action of glycoamidase. Three separate glycosylation sites were identified, each containing multiple glycans. The sugar analyses of the hydrolysates of the glycoprotein indicated that only GlcNAc and Man were present as building blocks, and the mass spectrometric data showed that Man3GlcNAc2-, GlcNAc2-4Man3GlcNAc2-, and possibly GlcNAc2Man2GlcNAc2- were the major glycan structures, distributed differently at the three sites. The three glycosylation sites match three of the nine sites glycosylated in human serum choline esterase, and one of them, Asn 106, is also found as one of two glycosylation sites in the homologous segment of thyroglobulin.
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PMID:Characterization of the disulfide bonds and the N-glycosylation sites in the glycoprotein from Rathke's gland secretions of Kemp's ridley sea turtle (Lepidochelys kempi). 878 16


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