Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To establish the chromosomal location of the human ACHE gene encoding the acetylcholine hydrolyzing enzyme acetylcholinesterase (ACHE, acetylcholine acetylhydrolase, E.C. 3.1.1.7), a human-specific polymerase chain reaction (PCR) procedure that supports the selective amplification of ACHE DNA fragments from human genomic DNA was employed with 19 human-hamster somatic cell hybrids carrying one or more human chromosomes. Informative ACHE-specific PCR fragments were produced from two cell lines, both of which include human chromosome 7, but not with DNA from 17 cell hybrids carrying various combinations of all human chromosomes other than 7. Fluorescent in situ hybridization of biotinylated ACHE DNA with metaphase chromosomes from human peripheral blood lymphocytes revealed prominent labeling on the 7q22 position. Therefore, further tests were performed to confirm the chromosome 7 location. DNA samples from the two cell lines including chromosome 7 and the ACHE gene were positive with PCR primers informative for the human cystic fibrosis CFTR gene, known to reside at the 7q31.1 position, but negative for the ACHE-related butyrylcholinesterase (BCHE, acylcholine acylhydrolase, E.C. 3.1.1.8) gene, mapped at the 3q26-ter position, confirming that these lines contain chromosome 7 but not chromosome 3. In contrast, three other cell lines including chromosome 3, but not 7, were BCHE-positive and ACHE-negative. In addition, genomic DNA from a sorted chromosome 7 library supported the production of ACHE- but not BCHE-specific PCR products, whereas with DNA from a sorted chromosome 3 library, the BCHE but not the ACHE fragment was amplified.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mapping the human acetylcholinesterase gene to chromosome 7q22 by fluorescent in situ hybridization coupled with selective PCR amplification from a somatic hybrid cell panel and chromosome-sorted DNA libraries. 138 Apr 83

Acetyl- and butyrylcholinesterase (ACHE, BCHE) from evolutionarily distant species display a high degree of primary sequence homology and have biochemically similar catalytic properties, yet they differ in substrate specificity and affinity for various inhibitors. The biochemical information derived from analyses of ACHE and BCHE from human, Torpedo, mouse, and Drosophila, as well as that from the recombinant forms of their natural variants and site-directed mutants, can currently be re-examined in view of the recent X-ray crystallography data revealing the three-dimensional structure of Torpedo ACHE. The picture that emerges deepens the insight into the biochemical basis for choline ester catalysis and the complex mechanism of interaction between cholinesterases and their numerous ligands.
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PMID:Excavations into the active-site gorge of cholinesterases. 141 13

1. Various hybridization approaches were employed to investigate structural and chromosomal interrelationships between the human cholinesterase genes CHE and ACHE encoding the polymorphic, closely related, and coordinately regulated enzymes having butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) activities. 2. Homologous cosmid recombination with a 190-base pair 5' fragment from BuChEcDNA resulted in the isolation of four overlapping cosmid clones, apparently derived from a single gene with several introns. The Cosmid CHEDNA included a 700-base pair fragment known to be expressed at the 3' end of BuChEcDNA from nervous system tumors and which has been mapped by in situ hybridization to the unique 3q26-ter position. In contrast, cosmid CHEDNA did not hybridize with full-length AChEcDNA, proving that the complete CHE gene does not include AChE-encoding sequences either in exons or in its introns. 3. The chromosomal origin of BuChE-encoding sequences was further examined by two unrelated gene mapping approaches. Filter hybridization with DNA from human/hamster hybrid cell lines revealed BuChEcDNA-hybridizing sequences only in cell lines including human chromosome 3. However, three BuChEcDNA-homologous sequences were observed at chromosomal positions 3q21, 3q26-ter, and 16q21 by a highly stringent in situ hybridization protocol, including washes at high temperature and low salt. 4. These findings stress the selectivity of cosmid recombination and chromosome blots, raise the possibility of individual differences in BuChEcDNA-hybridizing sequences, and present an example for a family highly similar proteins encoded by distinct, nonhomologous genes.
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PMID:Human acetylcholinesterase and butyrylcholinesterase are encoded by two distinct genes. 201 62

Cholinesterases are ubiquitous carboxylesterase type B enzymes capable of hydrolyzing the neurotransmitter acetylcholine which are transiently expressed in multiple germline, embryonic, and tumor cells. The acute poisoning effects of various organophosphorous compounds are generally attributed to their irreversible covalent interaction with cholinesterases and block of their catalytic activities. We have recently found a de novo inheritable amplification of a CHE gene encoding defective butyrylcholinesterase (acylcholine acyl hydrolase; EC 3.1.1.8) in a family under prolonged exposure to the agricultural organophosphorous insecticide methyl parathion. Further analysis revealed that both the CHE and the ACHE genes, encoding acetylcholinesterase (acetylcholine acetyl hydrolase; EC 3.1.1.7), are amplified in leukemias and platelet disorders and that the tumorigenic expression of these genes in ovarian carcinomas is associated with their frequent coamplification in these tumors. The amplification of CHE and ACHE genes in normal and tumor tissues might be analogous to the well-known amplification of other genes encoding target proteins to toxic compounds. As such, it could provide cells a selection advantage when exposed to organophosphorous poisons. Further, since cholinesterases appear to play developmentally important roles in multiple cell types, the amplification and overexpression of their corresponding genes might affect fertility, be related to the progression of various tumor types, and bear upon the ecological and clinical risks involved with the common use of organophosphorous poisons.
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PMID:Amplification of butyrylcholinesterase and acetylcholinesterase genes in normal and tumor tissues: putative relationship to organophosphorous poisoning. 240 80

To study the yet unknown role of the ubiquitous family of cholinesterases (ChoEases) in developing blood cells, the recently isolated cDNAs encoding human acetylcholinesterase (AcChoEase; acetylcholine acetylhydrolase, EC 3.1.1.7) and butyrylcholinesterase (BtChoEase; cholinesterase; acylcholine acylhydrolase, EC 3.1.1.8) were used in blot hybridization with peripheral blood DNA from various leukemic patients. Hybridization signals (10- to 200-fold intensified) and modified restriction patterns were observed with both cDNA probes in 4 of the 16 leukemia DNA preparations examined. These reflected the amplification of the corresponding AcChoEase and BtChoEase genes (ACHE and CHE) and alteration in their structure. Parallel analysis of 30 control samples revealed nonpolymorphic, much weaker hybridization signals for each of the probes. In view of previous reports on the effect of acetylcholine analogs and ChoEase inhibitors in the induction of megakaryocytopoiesis and production of platelets in the mouse, we further searched for such phenomena in nonleukemic patients with platelet production disorders. Amplifications of both ACHE and CHE genes were found in 2 of the 4 patients so far examined. Pronounced coamplification of these two related but distinct genes in correlation with pathological production of blood cells suggests a functional role for members of the ChoEase family in megakaryocytopoiesis and raises the question whether the coamplification of these genes could be causally involved in the etiology of hemocytopoietic disorders.
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PMID:Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: correlation with various leukemias and abnormal megakaryocytopoiesis. 273 15

A growing number of metabolic genetic defects can be diagnosed prenatally; however, the most common genetic diseases defy our efforts so far. Promising new avenues are mentioned. Efforts to diagnose neural tube defects in early pregnancy have gained wide acceptance. The most widely used method is alpha-fetoprotein (AFP)-determination in amnion fluid supplemented by ultrasound examination and particularly successfully by the ACHE-(acetyl-cholinesterase)gel test. In many countries, a general introduction of AFP-screening in maternal serum for neural tube defects is being considered. Two large field studies, each including some 24,000 patients, will soon be completed in Giessen and Hannover. They were designed to supplement the data from Great Britain in judging the advisability of mass screening of maternal serum AFP in the second trimenon in a low-incidence area such as Western Germany. The concluding discussion touches on future aspects of prenatal diagnosis and ethical considerations.
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PMID:[Prenatal recognition of genetic diseases and neural tube defects]. 619 31

Thirty wine growers have been examined in a preliminary study to define the morbidity related to the use of pesticides. The health status was defined (history, physical examination, liver and kidney function study, cholinesterase, EMG) before any exposure and some parameters were reassessed during exposure. Several results vary significantly during treatment with pesticides (ALT, AST, OCT, ACHE, BCHE). The initial health status is good, showing no systematic pathology. Several episodes of acute intoxication are mentioned in the patient's histories.
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PMID:[Wine growers and pesticides]. 715 69

Variant alleles of the butyrylcholinesterase gene, BCHE, have often been used to trace the genetic histories of populations. The D70G substitution in BCHE causes prolonged postanesthesia apnea ("atypical" phenotype); H322N substitution in the closely related acetylcholinesterase gene, ACHE, is the basis of the mutually incompatible Yt blood groups. In both genes, additional point mutations were reported to be linked to these phenotypically evident ones. To examine whether the intragenic linkage reported for the ACHE and BCHE mutations in Americans is universal, we studied frequencies of these mutations in trans-Caucasian Georgian Jews, a population that has remained relatively isolated for 1500 years. To this end we employed PCR amplification followed by DNA sequencing and enzymatic restriction and compared the frequencies we found to corresponding reported phenotype data. Georgian Jews' N322 ACHE was a rather low 7.0% and was totally linked to a P446 mutation, in agreement with a recent report. In BCHE, however, G70 was a relatively high 5.8%, and the V497 and T539 mutations were not found, either in Georgian or in Ashkenazi Jews, in contrast to reported findings in Americans. Our findings reveal distinct displays of ACHE and BCHE haplotypes in Georgian Jews and suggest different founder effects, genetic drifts, and/or selection pressures in the evolution of each of these genes.
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PMID:Population diversity and distinct haplotype frequencies associated with ACHE and BCHE genes of Israeli Jews from trans-Caucasian Georgia and from Europe. 780 14

A large cDNA fragment covering the complete sequence of the mature catalytic subunit of rabbit acetylcholinesterase (AChE) has been cloned and sequenced. This sequence was compared to that of rabbit butyrylcholinesterase [BChE; Jbilo, O. & Chatonnet, A. (1990) Nucleic Acids Res. 18, 3990]. Amino acid sequences of AChE and BChE have 51% identity. They both possessed a choline-binding site W84, a catalytic triad S200-H440-E327 and six cysteine residues (positions 67-94, 254-265, 402-521) in conserved sequence positions to those that form three intrachain disulfide bonds in all cholinesterases (by convention, numbering of amino acids is that used for Torpedo AChE). Rabbit AChE had a larger number of aromatic residues lining the active-site gorge than rabbit BChE (14 compared to 8, respectively) and a smaller number of potential N-glycosylation sites (3 compared to 8, respectively). Both catalytic subunits have a hydrophilic C-terminus (catalytic subunits of type T). Expression of acetylcholinesterase and butyrylcholinesterase genes (ACHE and BCHE) was studied in rabbit tissues and during development by a correlation of Northern-blot analysis and enzymic activities. This correlation was rendered difficult by the presence of an eserine-resistant esterase active on butyrylthiocholine in serum, liver and lung. When the contribution of this carboxylesterase was taken into account, brain was found as the richest source of BChE followed by lung and heart. Rabbit liver had a very low content of BChE that correlated with the low BChE activity in plasma. During development, BCHE transcripts were detected as early as day 10 post coitum, whereas ACHE transcripts appeared only on day 12.
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PMID:Acetylcholinesterase and butyrylcholinesterase expression in adult rabbit tissues and during development. 792 28

The acetylcholine hydrolysing cholinesterases control the termination of cholinergic signalling in multiple tissues and are targets for a variety of drugs, natural and man-made poisons and common insecticides. Molecular cloning and gene mapping studies revealed the primary structure of human acetyl- and butyrylcholinesterase and localized the corresponding ACHE and BCHE genes to the chromosomal positions 3q26-ter and 7q22, respectively. Several different point mutations in the coding region of BCHE were found to be particularly abundant in the Israeli population. Analytical expression studies in microinjected Xenopus oocytes have demonstrated that the biochemical properties of cholinesterases may be modified by rationalized site-directed mutagenesis and in chimeric ACHE/BCHE constructs. These properties are differently altered in the various allelic BCHE variants, conferring resistance to several anti-cholinesterases, which may explain the evolutionary emergence of these multiple alleles. At the clinical level, abnormal expression of both ACHE and BCHE and the in vivo amplification of the ACHE and BCHE genes has been variously associated with abnormal megakaryocytopoiesis, leukemias and brain and ovarian tumors. Moreover, antisense oligonucleotides blocking the expression of these genes were shown to interfere with hemocytopoiesis in culture, implicating these genes in cholinergic influence on cell growth and proliferation.
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PMID:Mutations and impaired expression in the ACHE and BCHE genes: neurological implications. 799 87


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