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)

Torpedo acetylcholinesterase (AcChoEase, EC 3.1.1.7) and human butyrylcholinesterase (BtChoEase, EC 3.1.1.8), while clearly differing in substrate specificity and sensitivity to inhibitors, possess 53% sequence homology; this permitted modeling human BtChoEase on the basis of the three-dimensional structure of Torpedo AcChoEase. The modeled BtChoEase structure closely resembled that of AcChoEase in overall features. However, six conserved aromatic residues that line the active-site gorge, which is a prominent feature of the AcChoEase structure, are absent in BtChoEase. Modeling showed that two such residues, Phe-288 and Phe-290, replaced by leucine and valine, respectively, in BtChoEase, may prevent entrance of butyrylcholine into the acyl-binding pocket. Their mutation to leucine and valine in AcChoEase, by site-directed mutagenesis, produced a double mutant that hydrolyzed butyrylthiocholine almost as well as acetylthiocholine. The mutated enzyme was also inhibited well by the bulky, BtChoEase-selective organophosphate inhibitor (tetraisopropylpyrophosphoramide, iso-OMPA). Trp-279, at the entrance of the active-site gorge in AcChoEase, is absent in BtChoEase. Modeling designated it as part of the "peripheral" anionic site, which is lacking in BtChoEase. The mutant W279A displayed strongly reduced inhibition by the peripheral site-specific ligand propidium relative to wild-type Torpedo AcChoEase, whereas inhibition by the catalytic-site inhibitor edrophonium was unaffected.
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PMID:Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis. 143 84

The distribution of amino acids between plasma, liver and brain was studied in adult male rats, fed a diet containing 8.7, 17 (control animals), 32 and 51% of protein during 15 days. The caloric intake was nearly equal in all groups. The highest food intake was observed in the animals on the low protein diet. Changes in plasma amino acids were variable. In contrast to the behavior of most amino acids in plasma, the branched chain amino acids were highest in the animals fed the 51% protein diet. Despite the low protein intake in the animals fed a 8.7% protein diet, the concentration of serine, glutamic acid, glutamine, glycine, alanine, methionine, isoleucine, leucine, phenylalanine and ornithine were significantly higher compared to control animals, whereas in those receiving a high protein diet, valine, leucine, tyrosine, tryptophan and histidine increased in relation to the increased protein and amino acid intake. The plasma amino acid patterns are not greatly influenced by the amino acid distribution in the food and the amount ingested. Alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and cholinesterase showed a two- to fivefold increased activity in the liver of animals consuming a high protein diet. In the brain, the concentration of valine, leucine, isoleucine, phenylalanine and tyrosine in animals receiving the low protein diet was higher than in controls and increased further with increasing protein content of the diet. Glutamine was increased in all dietary groups. The predicted influx of amino acids showed increasing influx rates in dependence of the plasma amino acid concentration. The entry of tyrosine and tryptophan and their brain concentration was inversely proportional to the protein content of the diet. In the present study which considers long-term adaptation to an increasing protein and amino acid intake in comparison to a balanced control protein diet, the levels of the indispensable amino acids were maintained within narrow limits in the brain and liver. The results indicate that inspite of a variable protein intake, the body tends to keep organ amino acids in relatively narrow limits favoring in this way amino acid homeostasis.
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PMID:Effect of different protein diets on the distribution of amino acids in plasma, liver and brain in the rat. 159 Jun 69

Quantitative and qualitative changes in acetylcholinesterase confer resistance to insecticides. We have constructed several Drosophila melanogaster strains producing various amounts of enzyme by P-mediated transformation. Toxicological analysis of these strains demonstrates that resistance to organophosphorus insecticides is correlated with the amount of acetylcholinesterase in the central nervous system. Resistance may also be qualitatively determined. Comparison of the Drosophila acetylcholinesterase gene between a resistant strain caught in the wild and a wild type susceptible strain only revealed one nucleotide transition resulting in the replacement of a phenylalanine by a tyrosine. Flies mutant for acetylcholinesterase and rescued with a minigene mutagenized for this same transition produced an altered enzyme which renders flies resistant to pesticides.
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PMID:Acetylcholinesterase. Two types of modifications confer resistance to insecticide. 162 20

Phenylalanine was evaluated for its ability to protect broiler chickens from the toxic effects of ochratoxin A (OA). A completely randomized 2-by-3 factorial design was utilized consisting of 0, .8, and 2.4% supplemental L-phenylalanine (Phe) and of 0 and 4 mg of OA per kg of diet. The basal diet contained 14% protein. Broilers were raised in battery brooders to 3 wk of age, when blood was collected and various hematological parameters were determined. The health status of the broilers was evaluated by assaying serum for various enzyme activities and metabolites using an automated, clinical chemistry analyzer. Adding OA to the broiler diets resulted in an increased concentration of serum hemoglobin as well as increased activity for cholinesterase and gamma glutamyl transferase but in decreased activity for aspartate amino transferase, lactate dehydrogenase, and alkaline-phosphatase activity as well as decreased concentrations of total triglyceride and of inorganic phosphorus. Supplemental Phe decreased the concentrations of hemoglobin and serum glucose. The regression slopes for Phe at 4 mg of OA per kg of diet were significant for uric acid, creatinine, total protein, albumin, and cholesterol suggesting that supplemental Phe improved the health status of the broilers fed diets containing OA with respect to these parameters.
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PMID:Impact of L-phenylalanine supplementation on the performance of three-week-old broilers fed diets containing ochratoxin A. 2. Effects on hematology and clinical chemistry. 197 19

In a previous paper (Burri et al., 1990), we have shown that experimental hyperphenylalaninemia (hyper-Phe) in 3-17 d-old rats leads to reduced myelinogenesis. Such treated rats recover during a 6 w low phenylalanine (Phe) period between days 17 and 59. In order to get more detailed information about the disturbed myelinogenesis and recovery, we measured in hyper-Phe rats the developmental pattern of two brain enzymes typical for myelination, cerebroside sulfotransferase (CST), and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), and other developmental parameters. Further, we correlated brain Phe levels with the brain damage in hyper-Phe rats, and we measured brain acetylcholinesterase (AChE) as a neuronal marker. Experimental hyper-Phe rats, injected between postnatal days 3 and 17 with alpha-methylphenylalanine and phenylalanine, showed a delayed age-dependent increase of CST activity, compared to that of controls. In hyper-Phe rats, CST peak activity was reached 2-4 d later, and was lower than in controls. The age-dependent decrease of the CST activity, however, started in test and control rats at the same time, at day 21. Between days 24 and 59, hyper-Phe rats had normal CST activity. CNP activity in hyper-Phe rats was lower than in controls from day 10 to 35, and recovered to normal values between days 35 and 59. Our results indicate that recovery from reduced myelinogenesis is possible after the period of fast myelination without compensatory increased CST activity. Further, the brain damage in test rats with Phe levels higher than average is more severe than in test rats with Phe levels lower than average; and there is no effect of hyperphenylalaninemia on brain neurons containing AChE.
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PMID:Reduced myelinogenesis and recovery in hyperphenylalaninemic rats. Correlation between brain phenylalanine levels, characteristic brain enzymes for myelination, and brain development. 209 83

The venom from Crotalus molossus nigrescens contains many activities including: hyde powder azure proteinase; N-benzoyl-arginine-ethyl-ester hydrolase; phospholipase; phosphodiesterase; desoxyribonuclease; fibrinogen coagulase; collagenase, fibrinolytic activity, and hemorrhagic factors. The venom, assayed with amounts of venom up to 50 micrograms protein per assay, does not contain acetylcholinesterase, phosphatase, amylase, ribonuclease, tyrosyl-ester hydrolase or hyaluronidase activities. The venom is lethal to mice with an i.p. LD50 of 2.35 mg/kg mouse. Fractionation of soluble venom by Sephadex G-75 separates at least five families of components. Fractions I-III contains all the enzymes, and fraction V have six small peptides. Further separation of fractions II-III on diethyl-amino-ethyl-cellulose columns at pH 8.0 and 8.3 gave pure proteinase E with a mol. wt of 21,390 and the following N-terminal amino acid sequence; Phe-Ala-Lys-Arg-Tyr-Val-Glx-Leu-Val-Ile-Val-Ala. A thrombin-like enzyme with a mol. wt of 75,000 was also purified from this venom by means of affinity and ion exchange chromatographies.
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PMID:Characterization of the venom from Crotalus molossus nigrescens Gloyd (black tail rattlesnake): isolation of two proteases. 218 98

The substrate specificity of lipoamidase, purified from the pig brain membrane with lipoyl 4-aminobenzoate (LPAB) as a substrate, was extensively studied. This single polypeptide was found to hydrolyse the bonding between amide, ester and peptide compounds. However, stringent structural requirements were found in the substrates, e.g. LPAB was hydrolysed, whereas biotinyl 4-aminobenzoate was not, as stated in our previous paper [Oizmui & Hayakawa (1990) Biochem. J. 266, 427-434]. The enzyme specifically recognized the whole molecular structure of the substrate, whereas it loosely recognized the bond structure of the substrate; e.g. the dipeptide Asp-Phe was not hydrolysed, whereas the methyl ester of Asp-Phe (aspartame) was. The exopeptidase activity was demonstrated by lipoamidase; however, longer peptides than the hexamer seemed not to be substrates. Lipoyl esters, which were electrically neutral, exhibited higher specificity with longer acyl groups. Molecular mass and molecular hydrophobicity (hydropathy) seemed to determine the substrate specificity. Lipoyl-lysine, acetylcholine and oligopeptides were hydrolysed at similar Km values; however, acetylcholine was hydrolysed at a velocity 100 times higher. Although many similar specificities were found between electric eel acetylcholinesterase and lipoamidase, distinctly different specificity was demonstrated with lipoyl compounds. The role of lipoamidase, which resides on the brain membrane and possesses higher specificity for hydrophobic molecules, remains to be elucidated.
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PMID:Lipoamidase is a multiple hydrolase. 222 21

The conformations of acetylcholine receptor from Torpedo californica in the absence and presence of agonists, antagonists, and local anesthetics were studied by circular dichroism (CD). Without ligands, the receptor had about 40% helix, 20% beta-sheets, and 10% beta-turns as analyzed from its far-UV CD spectrum. Its near-UV CD spectrum resembled that of acetylcholinesterase from the same source. None of the ligands studied altered the far-UV spectrum of the receptor. However, in the near-UV region, carbamylcholine and acetylcholine shifted the Phe and Tyr bands of AChR to less negative, whereas hexamethonium changed the Tyr bands to more negative, indicating that the site of binding of agonists and antagonists and their effect on the conformation of the receptor may be different. Decamethonium, procaine, and lidocaine had no effect on both the far- and near-UV CD spectra of acetylcholine receptor.
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PMID:Conformation of acetylcholine receptor in the presence of agonists and antagonists. 234 71

Hybridomas secreting monoclonal antibodies to Nippostrongylus brasiliensis antigens were generated by hybridization of IR983F myeloma cells with spleen cells from Lou/M/Wol rats infected with living third-stage larvae. Antibodies specific either for larval or worm antigens were identified by enzyme-linked immunosorbent assays with Nippostrongylus brasiliensis fragments, homogenates and secretions as antigens. The results demonstrate that all antibodies which recognized larval antigens (38 antibodies) also reacted with worm surfaces. Ten antibodies were specific only for worm antigens. Ten antibodies reacted with worm homogenate, three antibodies recognized components of worm secretion and 17 antibodies combined with acetylcholinesterase. The epitope specificity was investigated by the capacity of various glycosides, aminoacids, N-acetylneuraminic acid and phosphorylcholine to inhibit the binding to worm fragments. The analysis revealed that alpha-methylglucoside, alpha-methylmannoside, N-acetylglucosamine, N-acetylgalactosamine, fucose and the amino acids leucine, phenylalanine, tyrosine, serine, tryptophan did not combine with the antigen-binding sites of the antibodies. Proline, arginine and histidine, however, displayed inhibitory effects. With N-acetylneuraminic acid as inhibitor three groups of antibodies could be discriminated. At a concentration of 10-20 mM, phosphorylcholine was a potent inhibitor for all antibodies.
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PMID:Characterization of antigens of the nematode Nippostrongylus brasiliensis by monoclonal antibodies. 241 42

In rats treated with sodium cyanide (5-20 mg/kg, ip) dopamine was dose dependently decreased in the striatum within 60 sec. One of the main metabolites of dopamine in the central nervous system, 3-methoxy-4-hydroxyphenylacetic acid (HVA), was decreased in striatum, olfactory tubercle, and hippocampus. However, the oxidatively deaminated metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was not significantly altered in any of the brain regions studied. Naturally occurring levels of 3,4-dihydroxy-L-phenylalanine (L-dopa), as well as L-dopa accumulated after inhibition of the neuronal L-aromatic amino acid decarboxylase, increased in cyanide-treated rats. The dopamine receptor antagonist spiperone (0.05 mg/kg, ip) slightly increased the survival in acute cyanide intoxication. Sodium cyanide increased the levels of glutamine in frontal cortex and striatum at all doses studied. Glutamic acid was increased in the cerebellum, striatum, and hippocampus after sodium cyanide (5-10 mg/kg, ip). Higher doses decreased glutamic acid in the cerebellum, the frontal cortex, and the striatum. gamma-Aminobutyric acid (GABA) concentrations were diminished at high doses in all regions studied. Cyanide increased the levels of cyclic GMP in the cerebellum. In the striatum cyclic GMP was decreased after sodium cyanide (10 and 20 mg/kg). No significant alterations in the concentrations of acetylcholine or choline were seen in the striatum of cyanide-treated rats. The acetylcholinesterase inhibitor physostigmine and the muscarinic receptor antagonist atropine decreased the survival of mice given sodium cyanide. Acute cyanide intoxication thus produces rapid and fairly specific changes in central dopaminergic and GABA-ergic pathways.
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PMID:Acute cyanide intoxication and central transmitter systems. 286 59


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