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)

A series of (alkylthio)trifluoropropanones containing a heterocyclic moiety was synthesized. The compounds were tested for in vitro inhibition of four hydrolytic enzymes including insect juvenile hormone esterase (JHE), eel acetylcholinesterase (AChE), yeast lipase (LP), and bovine alpha-chymotrypsin. The I50 values ranged from 10(-3) to 10(-7) M. 3-(2-Pyridylthio)-1,1,1-trifluoro-2-propanone was found to be the most potent inhibitor as compared to the other tested heterocyclic analogues with an I50 value of 98 nM against JHE from the fifth-instar larvae of Trichoplusia ni. Results from X-ray crystallography showed that the compound exists in a tetrahedral gem-diol form stabilized by an intramolecular hydrogen bond in the solid state. X-ray crystallography of a less potent inhibitor, 3-(4-pyridylthio)-1,1,1-trifluoro-2- propanone, showed that it also exists in the hydrated form, but it lacks an intramolecular hydrogen bond. These results provide indirect support that trifluoromethyl ketones are transition-state mimic inhibitors of esterases, and the bearing of the results on the transition-state mimic theory is discussed. The I50 values against AChE were in the micromolar range. Compounds containing a imidazolyl, triazolyl, and pyrimidyl moiety showed the highest inhibition of this enzyme. Differential selectivity of inhibition was associated with the bond distances between the nitrogen and the carbonyl group as in the natural substrate, when measured in the molecules in their minimal energy conformations. Inhibition of LP was moderate to weak, when compared to JHE and AChE. None of the tested compounds showed significant inhibition of alpha-chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heterocyclic derivatives of 3-substituted-1,1,1-trifluoro-2-propanones as inhibitors of esterolytic enzymes. 213 80

Geotrichum candidum produces two extracellular lipases, I and II. A lipase II cDNA clone was isolated from a cDNA library by colony hybridization using the 32P-labeled fragment of lipase I cDNA isolated previously. The nucleotide sequence of lipase II cDNA determined by the dideoxy chain terminating method includes the N- and C-terminal amino acid sequences of lipase II, and the overall amino acid composition deduced from the cDNA coincides with that deduced on amino acid analysis of this protein. The cloned lipase II cDNA codes a protein of 544 amino acids and a part of the signal sequence of 13 amino acids. The peptide chain lengths of lipases I and II are the same, their overall identity being 84%. Furthermore, four Cys residues are completely conserved, which may participate in the formation of disulfide bridges. A homology search indicated that the G. candidum lipases and Candida cyclindracea lipase are homologous enzymes and that they are members of the cholinesterase family.
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PMID:cDNA cloning and characterization of Geotrichum candidum lipase II. 239 37

Amphiphilic detergent-soluble acetylcholinesterase (AChE) from Torpedo is converted to a hydrophilic form by digestion with phospholipase C from Trypanosoma brucei or from Bacillus cereus. This lipase digestion uncovers an immunological determinant which crossreacts with a complex carbohydrate structure present in the hydrophilic form of all variant surface glycoproteins (VSG) of T. brucei. This crossreacting determinant is also detected in human erythrocyte AChE after digestion with T. brucei lipase. From these results we conclude that the glycophospholipid anchors of protozoan VSG and of AChE of the two vertebrates share common structural features, suggesting that this novel type of membrane anchor has been conserved during evolution.
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PMID:The membrane-anchoring systems of vertebrate acetylcholinesterase and variant surface glycoproteins of African trypanosomes share a common antigenic determinant. 242 55

The experiment was carried out on Wistar rats receiving orally either oil or oily solution of methylbromophenvinfos (Polfos) either in a single dose of 0.5 LD50, or doses of 0.1 LD50 once daily for a period of 2, 4 or 6 weeks. The activities of cholinesterase (ChE), beta-glucuronidase (beta-glu), lipase and amylase were assayed in the blood serum, the activity of acetylcholinesterase (AChE)-in brain homogenates, and the activities of lipase and amylase-in homogenates of the pancreas. Cholinesterases were inhibited in the course of both acute and chronic poisoning with Polfos. During the acute poisoning a sharp increase in the activity of beta-glu in the blood serum, 1 and 2 h after the pesticide administration, was observed. Polfos inhibited lipase and amylase both after acute and chronic treatment.
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PMID:The effect of methylbromophenvinfos (Polfos) on some enzymes in vivo and in vitro. I. In vivo studies. 245 47

The sensitivity of acetylcholinesterases (AChEs) from Musca domestica and from Drosophila melanogaster to the phosphatidylinositol-specific phospholipase C from Bacillus cereus and to the glycosylphosphatidylinositol-specific phospholipase C from Trypanosoma brucei was investigated. B. cereus phospholipase C solubilizes membrane-bound AChE, and both phospholipases convert amphiphilic AChEs into hydrophilic forms of the enzyme. The lipases uncover an immunological determinant that is found on other glycosylphosphatidylinositol-anchored membrane proteins after the same treatment. This immunological determinant is also present on the native hydrophilic form of AChE. The polypeptide bearing the active site of the membrane-bound enzyme migrates faster during sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the same polypeptide from the soluble enzyme. We conclude that AChE from insect brain is attached to membranes via a glycophospholipid anchor. This anchor is covalently linked to the polypeptide bearing the active esterase site of the enzyme and can be cleaved by an endogenous lipase.
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PMID:Acetylcholinesterases from Musca domestica and Drosophila melanogaster brain are linked to membranes by a glycophospholipid anchor sensitive to an endogenous phospholipase. 283 Dec 98

The alterations in the distribution and activity of certain key enzymes, viz. alkaline phosphatase, acid phosphatase, glucose-6-phosphatase, cholinesterase and lipase, have been determined in the liver of rats (Rattus rattus albino) after experimental poisoning with hexavalent chromium. The histochemical and biochemical observations presented herewith provide visual evidence of chromium-induced inhibition of all these enzymes except lipase, which was found to be stimulated insignificantly. The results have been interpreted in terms of changes in the micro-environment of the cell, formation of apo-enzymes, metal-protein complexes, oxidative phosphorylation and finally with liver function.
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PMID:Dysenzymia induced by hexavalent chromium in rat liver. 299 22

We have isolated a COOH-terminal tryptic peptide from the hydrophobic globular (5.6 S) form of Torpedo californica acetylcholinesterase that exhibits divergence in amino acid sequence from the catalytic subunit of the dimensionally asymmetric (17 S + 13 S) enzyme. The divergent peptide could be recovered from the glycophospholipid-modified 5.6 S enzyme only after treatment with phosphatidylinositol-specific phospholipase C. Upon reduction, carboxymethylation with [14C]iodoacetate, and trypsin digestion the resultant peptides were purified by gel filtration followed by high performance liquid chromatography. The high performance liquid chromatography profiles of 14C-labeled cysteine peptides from lipase-treated 5.6 S enzyme revealed unique radioactive peaks which had not been present in digests of the asymmetric form. These peaks all yielded identical amino acid sequences. The difference in chromatographic behavior of the individual peptides most likely reflects heterogeneity in post-translational processing. Gas-phase sequencing and composition analysis are consistent with the sequence: Leu-Leu-Asn-Ala-Thr-Ala-Cys. Composition includes 2-3 mol each of glucosamine and ethanolamine which is indicative of modification by glycophospholipid. Glucosamine is also present in an asparagine-linked oligosaccharide. The two forms of acetylcholinesterase diverge after the threonine residue within this peptide sequence; the hydrophobic form terminates with cysteine whereas the asymmetric form extends for 40 residues beyond the divergence. The locus of divergence and absence of any other amino acid sequence difference suggest that the molecular forms of acetylcholinesterase arise from a single gene by alternative mRNA processing.
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PMID:Divergence in primary structure between the molecular forms of acetylcholinesterase. 333 34

The proposed system of continuous monitoring of enzyme activities is based primarily on the electrochemical behaviour of thiol compounds, and the experimental equipment is extremely simple. The determination of cholinesterase (EC 3.1.1.8) activity is described. The normal values obtained for men (73.9, s +/- 10.3 microkat/l) and for women (71.1, s +/- 10.2 microkat/l), lie within the usual range of analogous photometric methods. Systems for determination of the activities of alkaline phosphatase (EC 3.1.3.1) and adenosylhomocysteinase (EC 3.3.1.1) are described. The activity of aspartate aminotransferase (EC 2.6.1.1) is determined by a combination of enzyme reactions, in which CoA is released from acetyl-CoA. Analogous procedures are discussed for determinations of alanine aminotransferase (EC 2.6.1.2), lactate dehydrogenase (EC 1.1.1.27), lipase (EC 3.1.1.2), and phospholipase A2 (EC 3.1.1.4) activities, and for determination of substrates, e.g., acetate and carnitine. Possible determinations of an additional 199 enzyme activities and of some of substrates are suggested. By determining electrochemically active groups other than thiols this method becomes almost universally applicable.
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PMID:New system of continuous monitoring of enzyme activities and determination of some substrates. 344 Aug 58

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

Activities of 12 enzymes (amylase, lipase, cholinesterase, nonspecific carboxyl esterase, lactate dehydrogenase (LDH), alkaline phosphatase, glutamate-oxalacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), gamma-glutamyl transferase (gamma-GT), leucine aminopeptidase (LAP), malate dehydrogenase (MDH) and peroxidase) were determined in the perienteric fluid and homogenate of Ascaris suum. With the exception of amylase, all activities were higher in the homogenate than in the perienteric fluid. The enzyme activities in the perienteric fluid were then compared with those in the human serum. Comparable activities were demonstrated for LDH, LAP, lipase and alkaline phosphatase, markedly higher activities in perienteric fluid were demonstrated for MDH, GOT, GPT and amylase, and much lower for cholinesterase. No gamma-GT activity was detected in the perienteric fluid.
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PMID:Activities of some enzymes in the perienteric fluid of Ascaris suum. 619 63


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