Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ace-1 gene, which encodes acetylcholinesterase of class A, has been cloned and sequenced in C. briggsae and compared to its homologue in C. elegans. Both genes present an open reading frame of 1860 nucleotides. The percentages of identity are 80% and 95% at the nucleotide and aminoacid levels respectively. All residues characteristic of an acetylcholinesterase are found in conserved positions in C. briggsae ACE-1. The deduced C-terminus is hydrophilic, thus resembling the catalytic peptide T of vertebrate cholinesterases. Codon usage in both ace-1 genes appears to be lowly biased. This may indicate that these genes are lowly expressed. The splicing sites of the eight introns of ace-1 in C. elegans are conserved in C. briggsae, but introns are shorter in C. briggsae. No homology was found between intronic sequences in both species, except for the consensus border sequences.
 ...
PMID:Sequence comparison of ACE-1, the gene encoding acetylcholinesterase of class A, in the two nematodes Caenorhabditis elegans and Caenorhabditis briggsae. 891 24

Formation of the mixed pattern of neurotransmitter synthesis at intermediate stage of neuron functional differentiation involving interaction of nerve and epidermal growth factors (NGF and EGF) and also thyroxine was analysed histochemically. Analysis of change dynamics of acetyl cholinesterase catecholamine ratio influenced by NGF demonstrated its dependence on the cell type. Thyroxine potentiates NGF effect while EGF stimulates NGF-induced ACE increase only during the initial period.
 ...
PMID:[The role of polypeptide growth factors and hormones in the formation of neuromediator status of a sympathoadrenal cell line]. 960 69

A gene encoding a protein with strong homology with Caenorhabditis elegans and C. briggsae acetylcholinesterase ACE-1 was cloned from Meloidogyne incognita and M. javanica pre-parasitic juveniles. Both cDNAs have an ORF of 1968 bp for a deduced translation product of 656 amino acid residues. The key residues essential to acetylcholinesterase (AChE) structure and function are conserved in both sequences. M. incognita and M. javanica AChE share a homology of 98.8% at the amino acid level and 97% at the nucleotide level. Phylogenetic analysis showed that Meloidogyne and Caenorhabditis AChE form a cluster among AChE of triploblastic organisms. This Meloidogyne AChE is expressed in eggs, pre-parasitic juveniles and males and AChE activity was detected in situ in amphids of pre-parasitic juveniles. The opportunity of using AChE as a target in new strategies of nematode control is discussed.
 ...
PMID:Molecular cloning of an acetylcholinesterase gene from the plant parasitic nematodes, Meloidogyne incognita and Meloidogyne javanica. 1034 Apr 88

The effects of chronic sub-lethal doses (7-14 mg kg-1 a day for 15 days) of quinalphos were evaluated in adult male rats for changes in testicular morphology, circulatory concentrations of hormones (LH, FSH, prolactin and testosterone), activities of acetylcholinesterase (AChE) and angiotensin converting enzyme (ACE) as well as metabolism of biogenic amines (dopamine, noradrenaline and 5-hydroxytryptamine (5-HT)) in the hypothalamus and pituitary. Hormones were assayed by radioimmunoassay or chemiluminescent immunoassay (testosterone). The enzymes were estimated after spectrophotometry and the biogenic amines by HPLC-electrochemistry. Sub-lethal chronic administration of quinalphos resulted in: decreased testicular mass and AChE activity in central as well as peripheral organs; increased serum LH, FSH, prolactin and testosterone concentrations; decreased pituitary or increased testicular ACE activity; severe disruption of spermatogenesis with increasing doses of pesticide; and no significant effects on dopamine, noradrenaline or 5-HT concentrations in the hypothalamus or pituitary. Administration of oestradiol (50 micrograms per rat a day) during pesticide treatment resulted in: a significant decrease in the mass of the testis and accessory sex organs; decreases in serum LH, FSH, testosterone concentrations; an increase in prolactin concentration; and a decrease in dopamine or an increase in noradrenaline and 5-HT in the hypothalamus or pituitary. Oestradiol had a marked effect: in pesticide-treated animals, the pesticide effects were significantly reversed. This indicates that in pesticide toxicity, the hypothalamo-pituitary-gonadal axis is operational. Since many of the observed pesticide effects could be inhibited by oestradiol, it is suggested that the pesticide acts directly on the gonadotrophins. In conclusion, quinalphos decreases fertility in adult male rats by affecting the pituitary gonadotrophins.
 ...
PMID:Effects of an organophosphate pesticide, quinalphos, on the hypothalamo-pituitary-gonadal axis in adult male rats. 1079 23

We report the full coding sequences and the genomic organization of the four genes encoding acetylcholinesterase (AChE) in Caenorhabditis elegans and Caenorhabditis briggsae, in relation to the properties of the encoded enzymes. ace-1 and ace-2, located on chromosome X and I, respectively, encode two AChEs (ACE-1 and ACE-2) that present 35% identity. The C-terminal end of ACE-1 is homologous to the C terminus of T subunits of vertebrate AChEs. ACE-1 oligomerizes into amphiphilic tetramers. ACE-2 has a hydrophobic C terminus of H type. It associates into glycolipid-anchored dimers. In C. elegans and C. briggsae, ace-3 and ace-4 are organized in tandem on chromosome II, with only 356 nt and 369 nt, respectively, between the stop codon of ace-4 (upstream gene) and the ATG of ace-3. ace-3 produces only 5 % of the total AChE activity. It encodes an H subunit that associates into dimers of glycolipid-anchored catalytic subunits, which are highly resistant to the usual AChE inhibitors, and which hydrolyze butyrylthiocholine faster than acetylthiocholine. ACE-4 is closer to ACE-3 (54 % identity) than to ACE-1 or ACE-2. The usual sequence FGESAG surrounding the active serine residue in cholinesterases is changed to FGQSAG in ace-4. ACE-4 was not detected by our current biochemical methods, although the gene is transcribed in vivo. However the level of ace-4 mRNAs is far lower than those of ace-1, ace-2 and ace-3. The ace-2, ace-3 and ace-4 transcripts were found to be trans-spliced by both SL1 and SL2, although these genes are not included in typical operons. The molecular bases of null mutations g72 (ace-2), p1304 and dc2 (ace-3) have been identified.
 ...
PMID:Four genes encode acetylcholinesterases in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. cDNA sequences, genomic structures, mutations and in vivo expression. 1089 Dec 66

The biochemical effects of the 2-nitroimidazole hypoxic cell radiosensitizers KIN-804, KIN-806, and their analogues KIN-844 and TX-1877 on brain acetylcholinesterase (AChE) and hepatic free radical scavenging systems, such as reduced glutathione (GSH) and glucose-6-phosphate dehydrogenase (G-6-PDH) levels, and hepatic antioxidants, such as superoxide dismutase (SOD) and catalase, were evaluated in Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. The assay of brain AChE revealed nonsignificant changes with all drugs examined. To evaluate the hepatic metabolic capacity, groups of mice were divided into control, EAC-inoculated, 10-Gy local gamma-irradiated, and KIN-804, KIN-844, KIN-806, or TX-1877 (50 mg/kg body weight, i.p.) groups, and gamma-irradiation was combined with each drug. EAC inoculation markedly suppressed GSH, G-6-PDH, SOD, and catalase levels. On the other hand, treatment with gamma-irradiation significantly enhanced them. The treatment of EAC-bearing mice with each drug alone in the absence of gamma-irradiation revealed that KIN-806 and its derivative TX-1877 showed antitumor activity through their significant recovery of GSH and SOD levels, respectively, in the EAC-bearing mice group. Similarly, the combined treatment of EAC-bearing mice with gamma-irradiation with each of the drugs tested showed that KIN-806 and TX-1877 significantly increased GSH and SOD, and to a lesser extent G-6-PDH and catalase levels. On the other hand, KIN-804 and KIN-844 had only a nonsignificant effect on all parameters examined. In conclusion, these data reveal that the administration of KIN-806 and TX-1877 with or without subsequent gamma-irradiation, resulted in significant recovery of GSH and SOD activities that were inhibited by EAC inoculation.
 ...
PMID:Comparison of hypoxic cell radiosensitizers, KIN-804, KIN-844, KIN-806 and TX-1877, on brain and liver metabolizing capacities in mice bearing Ehrlich ascites carcinoma. 1203 98

A third variant of acetylcholinesterase (AChE A) secreted by the parasitic nematode Nippostrongylus brasiliensis has been isolated which shows 63-64% identity to AChE B and AChE C, with a truncated carboxyl terminus and a short internal insertion relative to AChEs from other species. Three of the fourteen aromatic residues which line the active site gorge in Torpedo AChE are substituted by non-aromatic residues (Y70T, W279D and F288M). All three enzymes have 8 cysteine residues in conserved positions, including 6 which have been implicated in disulphide bonds in other AChEs. Phylogenetic analysis suggests that these enzymes form a distinct group which evolved after speciation and are most closely related to ACE-2 of Caenorhabditis elegans. Recombinant AChE A secreted by Pichia pastoris was monomeric and hydrophilic, with a substrate preference for acetylthiocholine and negligible activity against butyrylthiocholine. A model structure of AChE A built from the coordinates of the Torpedo californica AChE suggests that W345 (F331 in Torpedo) limits the docking of butyrylcholine. This model is consistent with mutational analysis of the nematode enzymes. Expression of AChE A is regulated at the transcriptional level independently of the other 2 secreted variants, with maximal expression by fourth stage larvae and young adult worms. These enzymes thus appear to represent an unusual family of AChEs with conserved structural features which operate outside the normal boundaries of known functions in regulation of endogenous neurotransmitter activity.
 ...
PMID:A distinct family of acetylcholinesterases is secreted by Nippostrongylus brasiliensis. 1227 Jun 28

Alzheimer's disease (AD) is a genetically complex disorder associated with multiple genetic defects either mutational or of susceptibility. Current AD genetics does not explain in full the etiopathogenesis of AD, suggesting that environmental factors and/or epigenetic phenomena may also contribute to AD pathology and phenotypic expression of dementia. The genomics of AD is still in its infancy, but is helping us to understand novel aspects of the disease including genetic epidemiology, multifactorial risk factors, pathogenic mechanisms associated with genetic networks and genetically-regulated metabolic cascades. AD genomics is also fostering new strategies in pharmacogenomic research and prevention. Functional genomics, proteomics, pharmacogenomics, high-throughput methods, combinatorial chemistry and modern bioinformatics will greatly contribute to accelerating drug development for AD and other complex disorders. The multifactorial genetic dysfunction in AD includes mutational loci (APP, PS1, PS2) and diverse susceptibility loci (APOE, A2M, AACT, LRP1, IL1A, TNF, ACE, BACE, BCHE, CST3, MTHFR, GSK3B, NOS3) distributed across the human genome, probably converging in common pathogenic mechanisms that lead to premature neuronal death. Genomic associations integrate polygenic matrix models to elucidate the genomic organization of AD in comparison to the control population. Using APOE-related monogenic models it has been demonstrated that the therapeutic response to drugs (e.g., cholinesterase inhibitors, non-cholinergic compounds) in AD is genotype-specific. A multifactorial therapy combining three different drugs yielded positive results during 6-12 months in approximately 60% of the patients. With this therapeutic strategy, APOE-4/4 carriers were the worst responders and patients with the APOE-3/4 genotype were the best responders. Other polymorphic variants (PS1, PS2) also influence the therapeutic response to different drugs in AD patients, suggesting that the final pharmacological outcome is the result of multiple genomic interactions, including AD-related genes and genes associated with drug metabolism, disposition, and elimination. The pharmacogenomics of AD may contribute in the future to optimise drug development and therapeutics, increasing efficacy and safety, and reducing side-effects and unnecessary costs.
 ...
PMID:Pharmacogenomics for the treatment of dementia. 1245 80

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

A large number of methods are available for modeling quantitative structure-activity relationships (QSAR). We examine the predictive accuracy of several methods applied to data sets of inhibitors for angiotensin converting enzyme, acetylcholinesterase, benzodiazepine receptor, cyclooxygenase-2, dihydrofolate reductase, glycogen phosphorylase b, thermolysin, and thrombin. Descriptors calculated with CoMFA, CoMSIA, EVA, HQSAR, and traditional 2D and 2.5D descriptors were used for developing models with partial least squares (PLS). In addition, the genetic function approximation algorithm, genetic PLS, and back-propagation neural networks were used for deriving models from 2.5D descriptors (i.e., 2D descriptors and 3D descriptors calculated from CORINA structures and Gasteiger-Marsili charges). Predictive accuracy was assessed using designed test sets. It was found that HQSAR generally performs as well as CoMFA and CoMSIA; other descriptor sets performed less well. When 2.5D descriptors were used, only neural network ensembles were found to be similarly or more predictive than PLS models. In addition, we show that many cross-validation procedures yield similar estimates of the interpolative accuracy of methods. However, the lack of correspondence between cross-validated and test set predictive accuracy for four sets underscores the benefit of using designed test sets.
 ...
PMID:A comparison of methods for modeling quantitative structure-activity relationships. 1548 90


<< Previous 1 2 3 4 5 6 7 Next >>