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)

Detergent binding studies indicated that the neural enzyme, acetylcholinesterase, did not exhibit the properties of an integral membrane protein. The 11S form was isolated by affinity chromatography from a tryptic digest and the 14S and 18S forms in like manner from an undigested preparation. Studies were performed with [3H]TX-100 to determine the extent of binding by these forms and with catalase and human low density lipoprotein as reference proteins. All forms of the enzyme bound less than 0.04 mg TX-100/mg protein which is only slightly higher than binding by catalase and about 25 fold lower than the binding exhibited by low density lipoprotein.
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PMID:Evidence that eel acetylcholinesterase is not an integral membrane protein. 22 81

Decay-accelerating factor (DAF) is an integral membrane protein that inhibits amplification of the complement cascade on the cell surface. We and other investigators have shown that DAF is part of a newly characterized family of proteins that are anchored to the cell membrane by phosphatidylinositol (PI). The group includes the variant surface glycoprotein (VSG) of African trypanosomes, the p63 protein of Leishmania, acetylcholinesterase (AChE), alkaline phosphatase, Thy-1, 5'-nucleotidase, and RT6.2--an alloantigen from rat T cells. The structure of the membrane anchor has been best characterized for VSG, but chemical studies of the membrane anchors of AChE and Thy-1 suggest that similar glycolipid moieties anchor these proteins to the cell surface. In the VSG, the membrane anchor consists of an ethanolamine linked covalently to an oligosaccharide and glucosamine; the entire complex is anchored to the cell membrane by PI. Immunologically, this glycolipid defines an epitope, the cross-reacting determinant (CRD), that is only revealed after removal of the diacyl glycerol anchor by a phospholipase C. By Western blotting, we show here that DAF-S (DAF released from the membrane by PI-specific phospholipase C [PIPLC]) also contains CRD. Using a newly developed immunoradiometric assay (IRMA) in which the solid-phase capturing antibody is a monoclonal antibody to DAF and the second antibody is anti-CRD, we have been able to quantitate DAF-S. By IRMA, we show that the reaction between anti-CRD and DAF-S is specific, since the binding is competitively inhibited only by the soluble form of the VSG. These observations further support the concept that the glycolipid anchors of this new family of proteins have similar structures. DAF is also found as a soluble protein in various tissue fluids as well as in Hela cell supernatants. No evidence for the presence of the CRD epitope was found on these proteins, suggesting that these forms of DAF are not released from the surface of cells by endogenous phospholipases.
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PMID:Decay-accelerating factor (DAF) shares a common carbohydrate determinant with the variant surface glycoprotein (VSG) of the African Trypanosoma brucei. 243 27

Subcellular distribution and some extraction properties of acetylcholinesterase (AchE) (EC 3.1.1.7) and nonspecific cholinesterase (ChE) (EC 3.1.1.8) were studied in rat liver employing subcellular fractionation techniques. All purified subcellular fractions were enriched in total cholinesterase activity over the homogenate. Plasma membrane and Golgi fractions showed a significant enrichment in AchE activity, while ChE activity was enriched in both rough and smooth endoplasmic reticulum. Subcellular fractions were subjected to conditions that selectively release proteins having varying degrees of association to membranes. High-pH treatment (known to release peripheral and soluble proteins) extracted ChE activity, but more than 90% of AchE activity remained associated to the pellet. Solubility properties and molecular forms of AchE and ChE in this tissue were studied by extraction in high-salt medium with and without Triton X-100, followed by velocity sedimentation centrifugation. Most of AchE activity (88%) (41% G4 and 59% G2 + G1) was detergent soluble; 42% of ChE activity (detected only as G2 + G1) was high-salt soluble, whereas remaining ChE activity was detergent soluble. These results indicate not only a different subcellular location for both enzymes, but also point to a differential association to membranes. AchE behaves as an integral membrane protein and ChE behaves as a peripheral or a luminal soluble protein.
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PMID:Acetylcholinesterase and nonspecific cholinesterase activities in rat liver: subcellular localization, molecular forms, and some extraction properties. 261 91

The characterization of individual acetylcholinesterase (AChE) molecular form subcellular pools in adult mammalian skeletal muscle is a critical point when considering such questions as the origin, assembly, and neurotrophic regulation of these molecules. By correlating the results of differential extraction, in vitro collagenase digestion, and in situ pharmacologic probes of AChE molecular forms in endplate regions of adult rat anterior gracilis muscle, we have shown that: 1) 4.0S (G1) and 6.0S (G2) AChE are predominantly membrane-bound and intracellular; if an extracellular and/or soluble fraction of these forms exists, it cannot be adequately resolved by our methods; 2) 9-11S (globular) AChE activity is distributed between internal and external pools, as well as membrane-associated and soluble fractions; 3) 16.0S (A12) AChE is not an integral membrane protein and exists both intracellularly (25-30%) and extracellularly (70-75%).
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PMID:Subcellular localization of acetylcholinesterase molecular forms in endplate regions of adult mammalian skeletal muscle. 650 36

We have found that approximately one third of the total cell-associated acetylcholinesterase (AChE) is located on the plasma membrane of cultured chick embryo muscle, the remaining two thirds being found within the cells. This cell surface AChE appears to be an integral membrane protein. The surface enzyme is synthesized by the muscle cells in culture and is transported over a 2-3 hr period to the plasma membrane, where it accumulates at the rate of 2-3% of total surface AChE per hour. Once on the plasma membrane the AChE molecules are degraded by a process that exhibits first-order decay kinetics with a half-life of about 50 hr. Under the same experimental conditions, the acetylcholine receptor, a well described muscle cell integral membrane protein, has a half-life of approximately 19 hr. These studies provide the first direct evidence that the numbers of different muscle plasma membrane glycoprotein molecules are determined not only by differential rates of biosynthesis but also by differential rates of degradation. The intracellular AChE constitutes a rapidly turning-over pool of molecules. The rate of synthesis of AChE in culture is approximately 20% of the total cell-associated enzyme per hour, most of which is destined for secretion into the medium. Only a small portion of the newly synthesized AChE is retained on the plasma membrane. The time from synthesis to release of the enzyme is 2-3 hr. Using 3H-DFP to label the newly synthesized AChE, we can also show a quantitative transfer of AChE molecules from the intracellular to the extracellular compartments without any detectable residence time on the plasma membrane. By studying the synthesis transport and externalization of AChE we have defined the intracellular transport pathway and metabolic requirements for secretion in cultured muscle cells. These studies form the basis for a comparison of the metabolism of membrane-bound and secreted glycoproteins from this cell type.
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PMID:Synthesis, transport and fate of acetylcholinesterase in cultured chick embryos muscle cells. 744 73

Neuropathy target esterase (NTE) is an integral membrane protein present in all neurons and in some non-neural-cell types of vertebrates. Recent data indicate that NTE is involved in a cell-signalling pathway controlling interactions between neurons and accessory glial cells in the developing nervous system. NTE has serine esterase activity and efficiently catalyses the hydrolysis of phenyl valerate (PV) in vitro, but its physiological substrate is unknown. By sequence analysis NTE has been found to be related neither to the major serine esterase family, which includes acetylcholinesterase, nor to any other known serine hydrolases. NTE comprises at least two functional domains: an N-terminal putative regulatory domain and a C-terminal effector domain which contains the esterase activity and is, in part, conserved in proteins found in bacteria, yeast, nematodes and insects. NTE's effector domain contains three predicted transmembrane segments, and the active-site serine residue lies at the centre of one of these segments. The isolated recombinant domain shows PV hydrolase activity only when incorporated into phospholipid liposomes. NTE's esterase activity appears to be largely redundant in adult vertebrates, but organophosphates which react with NTE in vivo initiate unknown events which lead, after a delay of 1-3 weeks, to a neuropathy with degeneration of long axons. These neuropathic organophosphates leave a negatively charged group covalently attached to the active-site serine residue, and it is suggested that this may cause a toxic gain of function in NTE.
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PMID:Neuropathy target esterase. 1058 48

Exposure of cells to liposomes results in the release of integral membrane proteins. However, it is still controversial whether the release is due to spontaneous protein transfer from cells to liposomes or shed vesicles released from cells. We investigated this issue in an erythrocyte-liposome system by examining the location of acetylcholinesterase (AChE, an integral membrane protein marker), cholesterol (erythrocyte membrane lipid marker), hemoglobin (cytosolic protein marker), and a nonexchangeable lipid marker in liposomes in a sucrose density gradient at high resolution. The density distribution showed that AChE is not transferred to the liposomes but is located on small (about 50 nm) light (10-20 wt % sucrose) or large (about 200 nm) heavy shed vesicles (more than 30 wt % sucrose). AChE in the light shed-vesicle fraction markedly increased even after its level in the heavy fraction reached a plateau. AChE was also released from isolated heavy shed vesicles and accumulated in the small light shed-vesicle fraction in the presence of liposomes. After incubation of spherical erythrocytes (morphological index, 5.0) with liposomes, AChE hardly appeared in the heavy shed-vesicle fraction, and the majority (>99%) appeared in the light shed-vesicle fraction, indicating that AChE is released from both the erythrocytes and heavy shed vesicles to the light shed-vesicle fraction, which becomes rich in AChE. Our results demonstrated for the first time that GPI-linked proteins do not spontaneously transfer from erythrocytes to liposomes. Our study also suggests that in vivo GPI-linked membrane proteins do not spontaneously transfer between cell membranes but that some catalyst is needed.
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PMID:GPI-linked proteins do not transfer spontaneously from erythrocytes to liposomes. New aspects of reorganization of the cell membrane. 1092 43