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:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myotubes prepared from the Japanese quail embryo at 9 days gestation were cultivated in the presence of glycyl-L-glutamine (Gly-Gln, beta-endorphin C-terminal dipeptide) or glycyl-glutamic acid (Gly-Glu), and changes in the activity of acetylcholinesterase (AChE) molecular forms and binding of 125I-alpha-bungarotoxin (alpha BGT) to cell surface nicotinic acetylcholine receptors were measured. The A12 oligomer was the major form of AChE in the cultures. The activity of all molecular forms of the enzyme was increased in the presence of Gly-Gln, but Gly-Glu did not alter AChE activity. In cells infected with the temperature-sensitive mutant, La31C, of Rous sarcoma virus (ts-RSV) and transferred to the nonpermissive temperature, the A12 form of AChE was absent, but its activity could be induced following exposure of the cells to Gly-Gln. When cells treated in this way were incubated in the presence of collagenase, there was a small but significant loss of A12 AChE activity, indicating that Gly-Gln stimulated the activity of a pool of this oligomer which was mainly but not entirely intracellular. Neither Gly-Gln nor Gly-Glu influenced 125I-alpha BGT binding after exposure of the cells to the peptides for any duration. Neither Gly-Gln nor Gly-Glu influenced the accumulation of cyclic AMP in the cultures. beta-Endorphin is one of a family of peptides that coexist transiently with acetylcholine in lower motoneurones of vertebrates in the perinatal period. This report provides evidence for the selective trophic activity of one of its derivatives toward the postsynaptic cholinergic system in avian muscle cells.
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PMID:Glycyl-L-glutamine stimulates the accumulation of A12 acetylcholinesterase but not of nicotinic acetylcholine receptors in quail embryonic myotubes by a cyclic AMP-independent mechanism. 215 12

Under anesthesia with sodium pentobarbital, the sciatic nerves of rats were transected bilaterally, and a catheter was inserted into the central end of the left renal artery. After an initial flush, an Alzet pump was attached to the catheter, containing various concentrations of glycyl-L-glutamine (Gly-Gln), methylprednisolone sodium succinate (MePred), or both. Rats were sacrificed at intervals of 2, 4, or 6 days; the peripheral portions of the sciatic nerves were excised, homogenized, and centrifuged, and the supernates were assayed for acetylcholinesterase (AcChoEase; acetylcholine acetylhydrolase, EC 3.1.1.7) and protein. Significantly higher contents of AcChoEase over untreated transected controls were obtained (i) at 4 days posttransection in rats infused with 0.015 M Gly-Gln and (ii) at 6 days posttransection in rats infused with MePred at 3.0 mg.kg-1.hr-1 after an initial dose of 120 mg/kg with or without Gly-Gln.
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PMID:Effects of glycyl-L-glutamine and methylprednisolone on maintenance of acetylcholinesterase of transected rat sciatic nerves. 225 Dec 90

To study the molecular origin of the altered regulation of butyrylcholinesterase (BuChE) in nervous system tumors, BuChE complementary DNA (cDNA) sequences from human glioblastoma and neuroblastoma cDNA libraries were compared with BuChE cDNAs from normal fetal and adult tissues. A single 2.6-kilobase BuChE cDNA sequence was found in all normal tissues, whereas an additional alternatively terminated BuChE cDNA clone was found in both tumor libraries. The tumor-specific cDNA contained a 3',0.7-kilobase nontranslatable extension, as well as several nucleotide alterations in the normal polyadenylation site. Single-base mutations in the coding region of this unusual BuChE cDNA infer two amino acid substitutions: Asp70----Gly and Ser425----Pro. The Asp70----Gly change has recently been implicated with "atypical" BuChE, which is deficient in its capacity to hydrolyze succinylcholine. The 3.6-kilobase mRNA was less abundant in RNA blot hybridization than the 2.6-kilobase mRNA, which is in agreement with the low ratios between the 3.6- and 2.6-kilobase BuChE cDNA clones in glioblastoma and neuroblastoma libraries. Furthermore, size fractionation and microinjection of glioblastoma polyadenylated RNA, followed by enzyme activity and selective inhibition measurements, demonstrated two peaks of functional BuChE mRNA, the heavier one probably reflecting the longer transcripts. Chromosomal mapping of the 0.7-kilobase 3' fragment by in situ hybridization localized it to a unique 3q26-ter position, where we recently found an inheritably amplified "silent" defective CHE gene in a family exposed to the cholinesterase inhibitor methyl parathion. Our findings confirm previous genetic linkage mapping of the functional CHE gene to the 3q26-ter position and demonstrate that extended functional mRNA transcripts encoding a BuChE form with two modified amino acids are produced from this gene in glioblastoma and neuroblastoma cells.
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PMID:Expression of alternatively terminated unusual human butyrylcholinesterase messenger RNA transcripts, mapping to chromosome 3q26-ter, in nervous system tumors. 231 87

Purified human serum butyrylcholinesterase (approximately 90-kDa subunit) is known to exhibit aryl acylamidase and peptidase activity. Limited alpha-chymotrypsin digestion of the purified butyrylcholinesterase gave three major protein fragments of approximately 50 kDa, approximately 21 kDa and approximately 20 kDa. In our earlier studies [Rao and Balasubramanian (1989) Eur. J. Biochem. 179, 639-644] we characterized the approximately 20-kDa fragment and showed that it exhibited both butyrylcholinesterase and aryl acylamidase activities. In the present studies the approximately 50-kDa fragment is characterized. This fragment, after isolation by Sephadex G-75 chromatography from a chymotryptic digest of purified butyrylcholinesterase, exhibited only peptidase activity and was devoid of cholinesterase and aryl acylamidase activities. It could bind to a column of Ricinus communis agglutinin bound to Sepharose, indicating its glycosylated nature and the presence of galactose. The peptidase activity in the approximately 50-kDa fragment could be immuno-precipitated by a polyclonal antibody raised against purified butyrylcholinesterase. SDS-gel electrophoresis of this fragment isolated by R. communis agglutinin-Sepharose and Sephadex G-75 chromatography showed a protein band of approximately 50 kDa by silver staining. Amino-terminal sequence analysis of the approximately 50-kDa fragment gave the sequence of Gly-Pro-Thr-Val-Asp which corresponded to amino acid residues 291-295 in the butyrylcholinesterase sequence [Lockridge et al. (1987) J. Biol. Chem. 262, 549-557]. The combined results suggested that alpha-chymotrypsin digestion of human serum butyrylcholinesterase resulted in the formation of a approximately 20-kDa fragment exhibiting both cholinesterase and aryl acylamidase activities and a approximately 50-kDa fragment exhibiting only peptidase activity.
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PMID:Localization of the peptidase activity of human serum butyrylcholinesterase in a approximately 50-kDa fragment obtained by limited alpha-chymotrypsin digestion. 233 89

Purified human serum butyrylcholine esterase (approximately 90-kDa subunit), which also exhibits aryl acylamidase activity, was subjected to limited alpha-chymotrypsin digestion. Three major protein fragments of approximately 50 kDa, approximately 21 kDa and approximately 20 kDa were found to be produced, as observed by SDS-gel electrophoresis of the chymotryptic digest. The purified butyrylcholine esterase could fully bind to a Ricinus-communis-agglutinin-Sepharose column but after chymotryptic digestion about 15-20% of the enzyme activity remained unbound and was recovered in the run-through fractions. Sephadex G-75 chromatography of the chymotryptic digest showed an enzymatically active fragment eluted at an approximate molecular mass of 20 kDa, apart from the undigested butyrylcholine esterase eluted at the void volume. The butyrylcholine esterase fragment that did not bind to Ricinus communis agglutinin also was eluted at an approximate molecular mass of 20 kDa from a Sephadex G-75 column. This enzymatically active low-molecular-mass fragment from Sephadex G-75 chromatography showed a single protein band of approximately 20 kDa on SDS-gel electrophoresis. Neutral sugar analysis of the approximately 20 kDa fragment showed the presence of mannose only, whereas the undigested butyrylcholine esterase showed the presence of both mannose and galactose. Amino-terminal-sequence analysis of the approximately 20 kDa fragment showed the sequence Arg-Val-Gly-Ala-Leu, which agrees with amino acid residues 147-151 reported for human serum butyrylcholine esterase [Lockridge et al. (1987) J. Biol. Chem. 262, 549-557]. Both cholinesterase and aryl acylamidase activities were co-eluted in all chromatographic procedures. The results suggested that limited alpha-chymotrypsin digestion of human serum butyrylcholine esterase resulted in the formation of a approximately 20-kDa enzymatically active fragment with Arg147 as its N-terminal residue and which was devoid of galactose.
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PMID:Isolation of a galactose-free 20-kDa fragment exhibiting butyrylcholine esterase and aryl acylamidase activity from human serum butyrylcholine esterase by limited alpha-chymotrypsin digestion. 264 20

Rats were given glycyl-L-glutamine (Gly-Gln) by intraaortic infusion with Alzet osmotic pumps during the 48-hr period following the intraaortic administration of diisopropyl phosphorofluoridate (DFP) (10 mumol/kg). The infusion of 1.2 mumol of Gly-Gln per 24 hr resulted in a significant increase in the acetylcholinesterase (AcChoEase; acetylcholine acetylhydrolase, EC 3.1.1.7) activity of the gastrocnemius muscles over that of rats that received DFP only. At a total dose of 3.6 mumol per 24 hr, a diminished result was obtained; at 0.36 mumol per 24 hr, no effect was detectable. These findings, together with earlier ones, suggest that the neurotrophic effect of Gly-Gln or a similar endogenous factor on AcChoEase synthesis is a general phenomenon at sites of cholinergic transmission.
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PMID:Effect of glycyl-L-glutamine on the rate of regeneration of acetylcholinesterase in the rat gastrocnemius muscle after diisopropyl phosphorofluoridate administration. 272 74

A point mutation in the gene for human serum cholinesterase was identified that changes Asp-70 to Gly in the atypical form of serum cholinesterase. The mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was found by sequencing a genomic clone and sequencing selected regions of DNA amplified by the polymerase chain reaction. The entire coding sequences for usual and atypical cholinesterases were compared, and no other consistent base differences were found. A polymorphic site near the C terminus of the coded region was detected, but neither allele at this locus segregated consistently with the atypical trait. The nucleotide-209 mutation was detected in all five atypical cholinesterase families examined. There was complete concordance between this mutation and serum cholinesterase phenotypes for all 14 heterozygous and 6 homozygous atypical subjects tested. The mutation causes the loss of a Sau3A1 restriction site; the resulting DNA fragment length polymorphism was verified by electrophoresis of 32P-labeled DNA restriction fragments from usual and atypical subjects. Dot-blot hybridization analysis with a 19-mer allele-specific probe to the DNA amplified by the polymerase chain reaction distinguished between the usual and atypical genotypes. We conclude that the Asp-70----Gly mutation (acidic to neutral amino acid substitution) accounts for reduced affinity of atypical cholinesterase for choline esters and that Asp-70 must be an important component of the anionic site. Heterogeneity in atypical alleles may exist, but the Asp-70 point mutation may represent an appreciable portion of the atypical gene pool.
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PMID:Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase. 291 89

Thymulin, a metallononapeptide with the following aminoacid sequence: pyroGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-AsnOH is a thymic hormone involved in T cell differentiation requiring zinc to express biological activity as measured by the rosette assay. We established an enzyme immunoassay (EIA) for synthetic zinc-free thymulin with a thymulin-acetylcholinesterase conjugate as tracer and specific polyclonal rabbit antithymulin antibodies. The assay is performed as a classical competition assay in microtiter plates previously coated with mouse monoclonal IgG to rabbit IgG. A quantitative thymulin assay more sensitive than radioimmunoassays (RIAs) previously described was obtained with a sensitivity (IC50) of 32.5 +/- 5 pg/ml and a detection limit of 5 pg/ml. Analysis in the EIA of synthetic thymulin analogs showed that the minimal peptidic structure necessary for enzymatic tracer competition is the C-terminal part Lys3 to Asn9. It was also shown that the biologically active form of thymulin (zinc-bound) has the same immunoreactivity as zinc-free thymulin and that other thymic hormones, thymosin alpha 1 and thymopoietin II (or TP5) and unrelated short peptides do not cross-react with thymulin. These data demonstrate the specificity of this EIA for thymulin and show its suitability for application in biological fluids.
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PMID:An enzyme immunoassay for synthetic thymulin. 330 64

Intracarotid infusion of glycyl-L-glutamine (Gly-Gln) was shown previously to oppose the fall in the acetylcholinesterase and butyrylcholinesterase contents of the cat superior cervical ganglion (SCG) that otherwise follows preganglionic denervation. However, its effect was demonstrable only on the vascularly remote left SCG but not on the directly infused right SCG. Accordingly, it was concluded that a metabolite of Gly-Gln, formed in the blood, is an active neurotrophic factor. Glycyl-L-glutamic acid and L-glutamic acid were subsequently found to have a similar but less marked effect on both SCG. In the present study an alternative explanation has been tested: that Gly-Gln must combine slowly with some component of plasma to enable it to penetrate the ganglion cells and exert its neurotrophic effect. Findings are consistent with the latter proposal.
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PMID:Direct neurotrophic action of glycyl-L-glutamine in the maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat. 347 18

Purified human erythrocyte acetylcholinesterase was labeled by reductive radiomethylation with saturating amounts of [14C]formaldehyde and sodium cyanoborohydride. Acid hydrolysis and automated amino acid analysis permitted both identification of radiomethylated components by their coelution with radiomethylated standards and quantitation of these components. The methylated N-terminal amino acids glutamate and arginine were observed at levels of 0.66 and 0.34 residues, respectively, per 70-kilodalton subunit, and lysine residues were methylated on their epsilon-amino groups to a level of 7.40 residues per subunit [Haas, R., & Rosenberry, T.L. (1985) Anal. Biochem. 148, 154-162]. In addition, each subunit contained 1.35 residues of methylated ethanolamine and 0.98 residue of methylated glucosamine. Papain digestion cleaved the intact enzyme into two fragments, an enzymatically active hydrophilic fragment and a small hydrophobic fragment that represented the membrane-binding domain. The radiomethylated amino acids were quantitatively retained in the hydrophilic fragment, while the methylated ethanolamine and glucosamine were confined exclusively to the hydrophobic domain fragment. This fragment included the C-terminal dipeptide of the subunit. Peptide sequencing by manual Edman methods was combined with radiomethylation to demonstrate the sequence His-Gly-ethanolamine-Z for the hydrophobic domain fragment. The ethanolamine residue in this sequence is in amide linkage to the C-terminal Gly and is clearly distinct from the ethanolamine residues in Z which are susceptible to radiomethylation in the intact enzyme. Since Z also includes glucosamine and 2 mol of fatty acids [Roberts, W.L. & Rosenberry, T.L. (1985) Biochem. Biophys. Res. Commun. 133, 621-627], we conclude that the membrane-binding domain of human erythrocyte acetylcholinesterase is a covalently linked glycolipid at the C-termini of the subunits.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of amine components in a glycolipid membrane-binding domain at the C-terminus of human erythrocyte acetylcholinesterase. 352 71


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