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)

The present investigation revealed the effect of the organochlorine insecticide dieldrin at the dose level 0.25 LD50 at different time intervals on the concentration of 11 rat brain amino acids, on the activities of glutamic oxyacetic transaminase (GOT), glutamic pyruvic transaminase (GpT) and cholinesterase. The study was also extended to include the total protein content during the tested periods. The daily injection of dieldrin caused a marked decrease in the levels of glutamic acid, glutamine and taurine and an increase in the levels of aspartic acid, asparagine, GABA, glycine, lysine, serine, alanine and histidine. However, the maximal increase and decrease were recorded for most of the tested amino acids at the end of the tested period. The activity of the transaminases increased significantly. The recorded values of GOT were usually higher than GPT. Cholinesterase activity was inhibited thoroughly during all the experimental periods. Total protein content was decreased in the experiment; the minimal value was given 3 days after the injection.
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PMID:Effect of dieldrin injection on the level of certain amino acids and some enzymes in rat brain. 287 4

We describe a case of liver cirrhosis lacking the expected increase in serum thyroxin (T4)-binding globulin (TBG) despite abrupt, severe increases in aspartate and alanine aminotransferases (ASAT and ALAT) in serum. Sequential change in serum T4, triiodothyronine (T3), and TBG concentrations were also measured retrospectively in serum of 10 hospitalized patients with acute viral hepatitis. Although their mean T4 and TBG concentrations significantly exceeded those in 40 normal subjects (P less than 0.002 and P less than 0.001, respectively), these values were within the normal reference intervals in five patients. ASAT and ALAT concentrations were not significantly different in patients with increased TBG and patients with normal TBG, whereas mean concentrations of serum albumin and cholinesterase and mean prothrombin times (in percent) in the former group were significantly higher than those in the latter group (P less than 0.05, P less than 0.05, and P less than 0.001, respectively). For 60 samples with increased ASAT and ALAT, TBG and albumin or cholinesterase correlated significantly (r = 0.49, P less than 0.001 and r = 0.50, P less than 0.001, respectively), but not TBG and ASAT or ALAT. Collectively, these results suggest that the increase in serum TBG in acute hepatitis may reflect its synthesis in regenerating hepatocytes rather than a simple leakage from damaged hepatocytes.
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PMID:Are increases in thyroxin-binding globulin in patients with acute hepatitis ascribable to synthesis by regenerating hepatocytes? 312 18

In this paper, we show the existence of alternative splicing in the 3' region of the coding sequence of Torpedo acetylcholinesterase (AChE). We describe two cDNA structures which both diverge from the previously described coding sequence of the catalytic subunit of asymmetric (A) forms (Schumacher et al., 1986; Sikorav et al., 1987). They both contain a coding sequence followed by a non-coding sequence and a poly(A) stretch. Both of these structures were shown to exist in poly(A)+ RNAs, by S1 mapping experiments. The divergent region encoded by the first sequence corresponds to the precursor of the globular dimeric form (G2a), since it contains the expected C-terminal amino acids, Ala-Cys. These amino acids are followed by a 29 amino acid extension which contains a hydrophobic segment and must be replaced by a glycolipid in the mature protein. Analyses of intact G2a AChE showed that the common domain of the protein contains intersubunit disulphide bonds. The divergent region of the second type of cDNA consists of an adjacent genomic sequence, which is removed as an intron in A and Ga mRNAs, but may encode a distinct, less abundant catalytic subunit. The structures of the cDNA clones indicate that they are derived from minor mRNAs, shorter than the three major transcripts which have been described previously (14.5, 10.5 and 5.5 kb). Oligonucleotide probes specific for the asymmetric and globular terminal regions hybridize with the three major transcripts, indicating that their size is determined by 3'-untranslated regions which are not related to the differential splicing leading to A and Ga forms.
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PMID:Complex alternative splicing of acetylcholinesterase transcripts in Torpedo electric organ; primary structure of the precursor of the glycolipid-anchored dimeric form. 318 Nov 25

Acetylcholinesterase (EC 3.1.1.7) has been shown to possess an intrinsic peptidase activity. [Chubb et al. (1983), Neuroscience 10, 1369-1383]. To examine this activity further, the breakdown of a model hexapeptide (leu-trp-met-arg-phe-ala) LWMRFA was studied. Affinity-purified eel acetylcholinesterase rapidly cleaved the hexapeptide in a trypsin-like manner to produce two peptides (LWMR and FA). Acetylcholinesterase more slowly cleaved the C-terminal alanine residue from the peptide to yield LWMRF. Although the enzyme showed preference for cleaving the hexapeptide at its C-terminal, it was also able to cleave the N-terminal leucine residue form the tryptic product LWMR. Hydrolysis of the peptide at the tryptic site (arg4-phe5) was strongly inhibited by the trypsin inhibitor diisopropylfluorophosphate. Cleavage of the C-terminal alanine was only poorly inhibited by diisopropylfluorophosphate, but more strongly inhibited by metal-ion chelating agents, and it was increased in the presence of Zn2+ and Co2+. The pH optimum for cleavage at the tryptic site was 6, while that for the carboxypeptidase site was 8-9. These results show that acetylcholinesterase can hydrolyse peptides like a trypsin-like endopeptidase and a Zn2+- or Co2+-dependent exopeptidase, and they suggest that these two peptidase activities are associated with two separate active sites on the acetylcholinesterase molecule. As both peptidase activities eluted with acetylcholinesterase from a TSK 4000SW column when it was chromatographed by high-performance liquid chromatography, it is unlikely that the presence of either peptidase activity could be attributable to a contaminant in the acetylcholinesterase preparation. We suggest that acetylcholinesterase may be involved in the breakdown of bioactive peptides or their precursors in neuroendocrine cells.
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PMID:Acetylcholinesterase exhibits trypsin-like and metalloexopeptidase-like activity in cleaving a model peptide. 330 51

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

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

Oral administration of 0.5 mg/kg/day monocrotophos for 28 days caused death in one out of three animals. A dose of 2.0 mg/kg/day of monocrotophos was 100 percent lethal within 8-12 days after start of insecticide administration. Clinical symptoms were mainly characterised by ataxia, knuckling of limbs, progressive paralysis and prostration. Monocrotophos at both doses caused significant inactivation of erythrocyte cholinesterase (29.4-50.8%) and caused significant elevation in the serum levels of aspartate and alanine aminotransferases.
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PMID:Subacute toxicity of monocrotophos and its influence on circulating enzymes of Bubalus bubalis. 341 31

Active-site tryptic peptides were isolated from three genetic types of human serum cholinesterase. The active-site peptide was identified by labeling the active-site serine with [3H]diisopropylfluorophosphate. Peptides were purified by high-performance liquid chromatography. Amino acid composition and sequence analysis showed that the peptide from the usual genotype contained 29 residues with the sequence Ser-Val-Thr-Leu-Phe-Gly-Glu-Ser-Ala-Gly-Ala-Ala-Ser-Val-Ser-Leu-His-Leu- Leu-Ser-Pro-Gly-Ser-His-Ser-Leu-Phe-Thr-Arg. The active-site serine was the eighth residue from the N-terminal. The peptide containing the active-site serine from the atypical genotype contained 22 residues with the sequence Ser-Val-Thr-Leu-Phe-Gly-Glu-Ser-Ala-Gly-Ala-Ala-Ser-Val-Ser-Leu-His-Leu- Leu-Ser-Pro-Gly. The peptide from the atypical-silent genotype contained eight residues with the sequence Gly-Glu-Ser-Ala-Gly-Ala-Ala-Ser. Thus, the sequences of the atypical and atypical-silent active-site peptides were identical to the corresponding portions of the usual peptide.
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PMID:Amino acid sequence of the active site of human serum cholinesterase from usual, atypical, and atypical-silent genotypes. 374 70

Cholinesterases are serine esterases that rapidly hydrolyze the neurotransmitter acetylcholine. In humans, cholinesterases exhibit extensive polymorphism in terms of their substrate specificity, sensitivity to selective inhibitors, hydrophobicity, and cellular as well as subcellular localization. It is not yet known whether the various cholinesterase forms originate from different genes or are products of posttranscriptional and posttranslational processing. The extent to which these enzyme forms are homologous in their amino acid sequence is also not known. However, a consensus organophosphate-binding hexapeptide sequence Phe-Gly-Glu-Ser-Ala-Gly was found both in "true" acetylcholinesterase from the electric organ of Torpedo [McPhee-Quigley et al: J Biol Chem 260:12185-12189, 1985] and in "pseudocholinesterase" (butyrylcholinesterase) from human serum [Lockridge: "Cholinesterases--Fundamental and Applied Aspects." New York: de Gruyter pp 5-12, 1984], suggesting that this region in the protein is conserved in all cholinesterases. Based on this common sequence, we prepared synthetic oligodeoxynucleotides and used them as labeled probes to screen a cDNA library from fetal human brain mRNA, cloned in lambda gt10 phages. A cDNA clone of 770 nucleotides in length was isolated. It contains an open reading frame terminating with the sequence Ser-Val-Thr-Leu-Phe-Gly-Glu-Ser-Ala-Gly-Ala-Ala, which includes the consensus hexapeptide used for designing the DNA probe. Furthermore, the sequence of this 12-amino acid peptide is identical to the sequence reported for the organophosphate binding site of human serum pseudocholinesterase [Lockridge: "Cholinesterases--Fundamental and Applied Aspects." New York: de Gruyter, pp 5-12, 1984]. These findings confirm that the isolated clone is indeed part of a human cholinesterase cDNA.
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PMID:Use of synthetic oligodeoxynucleotide probes for the isolation of a human cholinesterase cDNA clone. 375 63

The intralaminar distributions of transmitter and nontransmitter enzyme activities and amino acid levels were determined in the midtemporal cortices from normal individuals and established cases of Alzheimer's disease. In the normal, choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities were relatively high in the outer cortical layers, particularly, for CAT, in the two granular layers (II and IV). Both activities were reduced in Alzheimer's disease at all, although generally most extensively in the outer and middle layers of the grey matter whereas activities were near normal in the white matter. Further, the enzyme distribution patterns of these cholinergic activities were also disrupted in Alzheimer's disease and the activity of CAT throughout the cortex was generally reduced to that found in the white matter. No such differences in distribution were found for two other enzymes, pseudocholinesterase and lactate dehydrogenase. Assessment of the gamma-aminobutyric acid (GABA) system in the normal revealed a much more extensive intralaminar variation in the enzyme, glutamate decarboxylase, compared with the level of GABA itself. In contrast with the cholinergic enzymes, neither the levels nor intralaminar patterns of GABA were altered in Alzheimer's disease. From an analysis of free amino acids at the different cortical levels, the cortical pattern of glutamic acid in the normal was different from that for GABA, aspartic acid, or nontransmitter amino acids such as alanine. Neither of the putative amino acids, glutamate or aspartate, was altered in Alzheimer's disease. These findings demonstrate the relatively selective nature of microchemical changes occurring in the cortex in Alzheimer's disease and suggest that a functional abnormality in cholinergic input to the outer neocortical layers (I-IV) with predominantly receptive and associative functions may be an important feature of the disease.
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PMID:Intralaminar neurochemical distributions in human midtemporal cortex: comparison between Alzheimer's disease and the normal. 614 24


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