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

---

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

ace-1 and ace-2 genes encoding acetylcholinesterase in the nematode Caenorhabditis elegans present 35% identity in coding sequences but no homology in noncoding regions (introns, 5'- and 3'-untranslated regions). A 5'-region of ace-2 was defined by rescue of ace-1;ace-2 mutants. When green fluorescent protein (GFP) expression was driven by this regulatory region, the resulting pattern was distinct from that of ace-1. This latter gene is expressed in all body-wall and vulval muscle cells (Culetto et al., 1999), whereas ace-2 is expressed almost exclusively in neurons. ace-3 and ace-4 genes are located in close proximity on chromosome II (Combes et al., 2000). These two genes were first transcribed in vivo as a bicistronic messenger and thus constitute an ace-3;ace-4 operon. However, there was a very low level of monocistronic mRNA of ace-4 (the upstream gene) in vivo, and no ACE-4 enzymatic activity was ever detected. GFP expression driven by a 5' upstream region of the ace-3;ace-4 operon was detected in several muscle cells of the pharynx (pm3, pm4, pm5 and pm7) and in the two canal associated neurons (CAN cells). A dorsal row of body-wall muscle cells was intensively labelled in larval stages but no longer detected in adults. The distinct tissue-specific expression of ace-1, ace-2 and ace-3 (coexpressed only in pm5 cells) indicates that ace genes are not redundant.
...
PMID:Multiple ace genes encoding acetylcholinesterases of Caenorhabditis elegans have distinct tissue expression. 1291 46

Nematodes are unusual in that diverse molecular forms of acetylcholinesterase are the product of distinct genes. This is best characterised in the free living organism Caenorhabditis elegans, in which 3 genes are known to give rise to distinct enzymes, with a fourth likely to be non-functional. ACE-1 is an amphiphilic tetramer associated with a hydrophobic non-catalytic subunit, analogous to vertebrate T enzymes, whereas ACE-2 and ACE-3 are glycosylphosphatidylinositol-linked amphiphilic dimers. The different ace genes show distinct anatomical patterns of expression in muscles, sensory neurons and motor neurons, with only a few examples of coordinated expression. Clear homologues of ace-1 and ace-2 have now been isolated from a variety of parasitic nematodes, and the predicted proteins have very similar C-terminal amino acid sequences, implying an analogous means of anchorage to membranes. In addition to these membrane-bound enzymes, many parasitic nematodes which colonise mucosal surfaces secrete acetylcholinesterases to the external (host) environment. These hydrophilic enzymes are separately encoded in the genome, so that some parasites may thus have a total complement of six ace genes. The secretory enzymes have been characterised from the intestinal nematode Nippostrongylus brasiliensis and the lungworm Dictyocaulus viviparus. These show a number of common features, including a truncated C-terminus and an insertion at the molecular surface, when compared to other nematode acetylcholinesterases. Although the function of these enzymes has not been determined, they most likely alter host physiological responses to promote survival of the parasite.
...
PMID:Nematode acetylcholinesterases are encoded by multiple genes and perform non-overlapping functions. 1624 3

Acetylcholine (ACh) is one of an array of neurotransmitters used by invertebrates and, analogous to vertebrate nervous systems, acetylcholinesterase (AChE) regulates synaptic levels of this transmitter. Similar to other invertebrates, nematodes possess several AChE genes. This is in contrast to vertebrates, which have a single AChE gene, transcripts of which are alternatively spliced to produce different types of the enzyme which vary at their C-termini. Parasitic nematodes have a repertoire of AChE genes which include those encoding neuromuscular AChEs and those genes which code for secreted AChEs. The latter proteins exist as soluble monomers released by the parasite during infection and these AChE are distinct from those enzymes which the nematodes use for synaptic transmission in their neuromuscular system. Thus far, Dictyocaulus viviparus is the only animal-parasitic nematode for which distinct genes that encode both neuromuscular and secreted AChEs have been defined. Here, we describe the isolation and characterization of a cDNA encoding a putative neuromuscular AChE from D. viviparus which contains a tryptophan amphiphilic tetramerization (WAT) domain at its C-terminus analogous to the common 'tailed' AChE form found in the neuromuscular systems of vertebrates and in the ACE-1 AChE from Caenorhabditis elegans. This enzyme differs from the previously isolated, D. viviparus neuromuscular AChE (Dv-ACE-2), which is a glycosylphosphatidylinositol-anchored variant analogous to vertebrate 'hydrophobic' AChE.
...
PMID:A tryptophan amphiphilic tetramerization domain-containing acetylcholinesterase from the bovine lungworm, Dictyocaulus viviparus. 1671 58

A previously developed method to identify members of the Culex pipiens complex exploiting polymorphisms in a nuclear intron (acetylcholinesterase [ACE] based-assay) cannot differentiate the two forms of Cx. pipiens: form pipiens and form molestus. Notably, the two forms seem to differ extensively in behavior and physiology and likely have very different epidemiologic importance. Because they are morphologically indistinguishable, molecular methods are critical for the evaluation of their relative importance. Although the two forms of Cx. pipiens have been distinguished using a panel of microsatellite loci, such a protocol is laborious and expensive. We developed a rapid assay based on polymorphisms in the flanking region of a microsatellite locus. Used in conjunction with the ACE-assay, this new assay allows the identification of pure and hybrid populations of the two Cx. pipiens forms as well as those including Cx. quinquefasciatus. We discuss the usefulness of the method as well as limitations to its application.
...
PMID:Rapid assay to identify the two genetic forms of Culex (Culex) pipiens L. (Diptera: Culicidae) and hybrid populations. 1689 27

In insects, selection of insecticide-insensitive acetylcholinesterase (AChE) is a very common resistance mechanism. Mosquitoes possess both AChE1 and AChE2 enzymes and insensitivity is conferred by single amino-acid changes located near the active site of the synaptic AChE1. Only two positions have been reported so far to be involved in resistance, suggesting a very high structural constraint of the AChE1 enzyme. In particular, the G119S substitution was selected in several mosquitoes' species and is now largely spread worldwide. Yet, a different type of AChE1 insensitivity was described 10 years ago in a Culex pipiens population collected in Cyprus in 1987 and fixed thereafter as the ACE-R strain. We report here the complete amino-acid sequence of the ACE-R AChE1 and show that resistance is associated with a single Phe-to-Val substitution of residue 290, which also lines the active site. Comparison of AChE1 activities of the recombinant F290V protein and ACE-R mosquito extracts confirmed the causal role of the substitution in insensitivity. Biochemical characteristics of the mutated protein indicated that the resistance level varies with the insecticide used. A molecular diagnosis test was designed to detect this mutation and was used to show that it is still present in Cyprus Island.
...
PMID:A new amino-acid substitution in acetylcholinesterase 1 confers insecticide resistance to Culex pipiens mosquitoes from Cyprus. 1717 45

Recent studies demonstrate that the therapeutic response in Alzheimer's disease (AD) is genotype-specific. More than 200 genes are potentially associated with AD pathogenesis and neurodegeneration, and approximately 1,400 genes distributed across the human genome account for 20 to 95% of variability in drug disposition and pharmacodynamics. Cytochrome P450 enzymes encoded by genes of the CYP superfamily, such as CYP1A1 (15q22-q24), CYP2A6 (19q13.2), CYP2C8 (10q24), CYP2C9 (10q24), CYP2C19 (10q24.1-q24.3), CYP2D6 (22q13.1), CYP2E1 (10q24.3-qter), and CYP3A5 (7q22.1), acting as terminal oxidases in multicomponent electron transfer chains which are called P450-containing monooxygenase systems, metabolize more than 90% of drugs. Some of the enzymatic products of the CYP gene superfamily can share substrates, inhibitors and inducers whereas others are quite specific for their substrates and interacting drugs. Some cholinesterase inhibitors (tacrine, donepezil, galantamine) are metabolized via CYP-related enzymes, especially CYP2D6, CYP3A4, and CYP1A2. The distribution of CYP2D6 genotypes in the Spanish population is the following: (a) Extensive Metabolizers (EM)(51.61%): *1/*1, 47.10%; and *1/*10, 4.52%; (b) Intermediate Metabolizers (IM)(32.26%): *1/*3, 1.95%; *1/*4, 17.42%; *1/*5, 3.87%; *1/*6, 2.58%; *1/*7, 0.75%; *10/*10, 1.30%; *4/*10, 3.23%; *6/*10, 0.65%; and *7/*10, 0.65%; (b) Poor Metabolizers (PM)(9.03%): *4/*4, 8.37%; and *5/*5, 0.65%; and (c) Ultrarapid Metabolizers (UM)(7.10%): *1xN/*1, 4.52%; *1xN/*4, 1.95%; and CYP2D6 gene duplications, 0.65%. PMs and UMs also accumulate genotypes of risk associated with APOE-, PS-, ACE-, and PRNP-related genes. Approximately, 15% of the AD population may exhibit an abnormal metabolism of cholinesterase inhibitors; about 50% of this population cluster would show an ultrarapid metabolism, requiring higher doses of cholinesterase inhibitors to reach a therapeutic threshold, whereas the other 50% of the cluster would exhibit a poor metabolism, displaying potential adverse events at low doses. In AD patients treated with a multifactorial therapy, including cholinesterase inhibitors (e.g., donepezil), the best responders are the CYP2D6-related EMs and IMs, and the worst responders are PMs and UMs. In addition, the presence of the APOE-4 allele in genetic clusters integrating CYP2D6 and APOE genotypes contributes to deteriorate the therapeutic outcome. From these data, it can be postulated that pharmacogenetic and pharmacogenomic factors are responsible for 75-85% of the therapeutic response in AD patients treated with conventional drugs.
...
PMID:Pharmacogenetic aspects of therapy with cholinesterase inhibitors: the role of CYP2D6 in Alzheimer's disease pharmacogenetics. 1790 53

The identification of the members of the Culex pipiens L. complex in arbovirus surveillance programs relies heavily on the use of morphology. In this work, we studied Cx. pipiens complex male mosquitoes collected from nine different locations, from northern, southern, and the hybrid zone sites in North America; Cairo, Egypt; and Nairobi, Kenya. Specimens were identified using DV/D ratio and also using amplification of the acetylcholinesterase (ACE.2) gene by both conventional and real-time polymerase chain reaction, and examination of the CQ11 locus. Consistent with previous findings, the morphological and molecular identifications did not always agree, particularly in regions of extensive introgression. There was an increased frequency of hybrid forms in late summer and early fall in Champaign Co., IL, that is north of the previously described Cx. pipiens complex hybrid zone. This represents an expansion of the North American hybrid zone. The biological and epidemiological relevance of the high degree of introgression and the late season increase in the proportion of intermediate forms is discussed.
...
PMID:Identification of male specimens of the Culex pipiens complex (Diptera: Culicidae) in the hybrid zone using morphology and molecular techniques. 1840 35

A cDNA, named Dd-ace-2, encoding an acetylcholinesterase (AChE, EC3.1.1.7), was isolated from sweet-potato-stem nematode, Ditylenchus destructor. The nucleotide and amino acid sequences among different nematode species were compared and analyzed with DNAMAN5.0, MEGA3.0 softwares. The results showed that the complete nucleotide sequence of Dd-ace-2 gene of Ditylenchus destructor contains 2425 base pairs from which deduced 734 amino acids (GenBank accession No. EF583058). The homology rates of amino acid sequences of Dd-ace-2 gene between Ditylenchus destructor and Meloidogyne incognita, Caenorhabditis elegans, Dictyocaulus viviparous were 48.0%, 42.7%, 42.1% respectively. The mature acetylcholinesterase sequences of Ditylenchus destructor may encode by the first 701 residues of deduced 734 amino acids.The conserved motifs involved in the catalytic triad, the choline binding site and 10 aromatic residues lining the catalytic gorge were present in the Dd-ace-2 deduced protein. Phylogenetic analysis based on AChEs of other nematodes and species showed that the deduced AChE formed the same cluster with ACE-2s.
...
PMID:[Molecular cloning and characterization of an acetylcholinesterase gene Dd-ace-2 from sweet potato stem nematode Ditylenchus destructor]. 1846 7

We have undertaken a study on variations in cholinesterase (ChE) genes in relation to cardiovascular (CV) function and the metabolic syndrome. Peripheral and central nervous system control of cardiovascular (CV) function mediated through cholinergic pathways is critical in homeostatic maintenance of blood pressure and responsiveness to stress. For acetylcholinesterase (AChE; EC 3.1.1.7) our focus is to identify single nucleotide polymorphisms (SNPs) in the gene that are linked to cardiovascular function. For butyrylcholinesterase (BChE; EC 3.1.1.8) we examined whether BChE activity correlated with parameters of the metabolic syndrome and cardiovascular function. ChE can be found in whole blood enabling a characterization of biochemical phenotype in addition to correlating genotype with phenotypic physiologic responses. Analysis of enzymatic activity was determined spectrophotometrically in blood samples from twin and other subject registries. Correlation analysis revealed significant relationships between enzyme activity and certain CV endpoints. Linkage analysis with data from a dizygotic (DZ) twin set showed a suggestive linkage at the BChE locus, and statistical analysis revealed a high correlation between BChE activity and variables associated with cardiovascular risk and the metabolic syndrome. Pattern of within-pair twin correlations by zygosity and the ACE model-fitting findings suggest the major source of this variation (65%) is attributable to an additive genetic component. To date 19 SNPs have been identified by the re-sequencing of AChE including four nonsynonymous coding SNPs (cSNPs).
...
PMID:The cholinesterases: analysis by pharmacogenomics in man. 1854 Dec 29

Migration of plant-parasitic nematode infective larval stages through soil and invasion of roots requires perception and integration of sensory cues culminating in particular responses that lead to root penetration and parasite establishment. Components of the chemoreceptive neuronal circuitry involved in these responses are targets for control measures aimed at preventing infection. Here we report, to our knowledge, the first isolation of cyst nematode ace-2 genes encoding acetylcholinesterase (AChE). The ace-2 genes from Globodera pallida (Gp-ace-2) and Heterodera glycines (Hg-ace-2) show homology to ace-2 of Caenorhabditis elegans (Ce-ace-2). Gp-ace-2 is expressed most highly in the infective J2 stage with lowest expression in the early parasitic stages. Expression and functional analysis of the Globodera gene were carried out using the free-living nematode C. elegans in order to overcome the refractory nature of the obligate parasite G. pallida to many biological studies. Caenorhabditis elegans transformed with a GFP reporter construct under the control of the Gp-ace-2 promoter exhibited specific and restricted GFP expression in neuronal cells in the head ganglia. Gp-ACE-2 protein can functionally complement its C. elegans homologue. A chimeric construct containing the Ce-ace-2 promoter region and the Gp-ace-2 coding region and 3' untranslated region was able to restore a normal phenotype to the uncoordinated C. elegans double mutant ace-1;ace-2. This study demonstrates conservation of AChE function and expression between free-living and plant-parasitic nematode species, and highlights the utility of C. elegans as a heterologous system to study neuronal aspects of plant-parasitic nematode biology.
...
PMID:Functional characterisation of a cyst nematode acetylcholinesterase gene using Caenorhabditis elegans as a heterologous system. 1936 33


<< Previous 1 2 3 Next >>

---