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)

Three groups of 200-gm rats were injected subcutaneously with neostigmine methylsulfate (1 mg/kg/day) for 7, 30, and 100 days. Electrophysiological changes were assessed in vitro, using microelectrode techniques to examine diaphragm muscles of treated and untreated animals. Miniature end-plate potential (MEPP) amplitude decreased in neostigmine-treated preparations. Guanidine hydrochloride enhances transmitter release and increases MEPP frequency in control preparations. Neostigmine-treated animals examined between 6 to 72 hours after discontinuation of neostigmine therapy showed impaired response to the facilitating influence of guanidine. Recovery of response to guanidine was inversely related to length of treatment with neostigmine. Results of electron-microscopic examination of motor end-plates in treated animals revealed ultrastructural changes, including simplified end-plates, and, occasionally, multiple, separate, junctional regions. Therefore, the chronic administration of cholinesterase inhibitors in man may have a deleterious effect, as well as a transient beneficial one.
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PMID:Neostigmine methylsulfate. Does it have a chronic effect as well as a transient one? 17 68

In 4 patients with clinical signs of dermatomyositis, confirmed by electromyography and muscle biopsy, a form of muscle fatigue was detected which was expressed clinically by predominantly proximal motor deficit, with phonation and deglutition disturbances, slightly influenced by prostigmine. In all patients, stimulation of the ulnar nerve at 3--10 Hz induced a decrement of muscle-evoked potentials in abductor digiti minimi and at 15--50 Hz an increment at the end of the trains (1.2 sec in duration) of repetitive stimulation (preceded in two cases by a decrement in the response to the fifth stimulus in the train). Stimulation at 30 Hz for 10 sec resulted in a transient facilitation, followed (at 3 Hz stimulation) by postactivation exhaustion which disappeared after 5--15 min. The post-tetanic facilitation, the incremental response and the myasthenic symptoms reverted to normal under treatment with corticosteroids, an immunosuppressor agent and guanidine hydrochloride. A mixed, pre- and postsynaptic mechanism is presumed to underlie the muscle fatigue in our patients. Electron microscopy of muscle biopsies disclosed zones of necrosis and, in incipient stages, large agglomerations of glycogen that had disorganized the structure of myofibrils. The end-plates in the biopsies were larger than normal and the cholinesterase reaction was hyperactive. Serum immunoelectrophoretic and electrophoretic data--increase of IgG and IgM, decrease of IgA and hypergammaglobulinaemia -- point to a possible autoimmune mechanism of the neuromuscular disorders in our patients.
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PMID:Myasthenia in patients with dermatomyositis: clinical, electrophysiological and ultrastructural studies. 21 37

The major C4 component of human serum cholinesterase was highly purified by a two-step procedure involving chromatography on DEAE-cellulose and preparative disc electrophoresis. The final product was about 8 000-fold purified with a yield of 64%. The subunit structure was determined by 8M urea polyacrylamide disc electrophoresis and by the sedimentation equilibrium centrifugation method in 5M guanidine hydrochloride. It was found that the C4 enzyme has a tetrameric structure. The subunits are equal in size and charge and a molecular weight comparable to that of the C1 enzyme from native serum. The major C4 enzyme and the minor C1 enzyme were subjected to an 'active enzyme centrifugation'. It was found that the C4 enzyme was a tetramer and the C1 enzyme was a monomer in the presence of substrate. The number of diisopropylphosphofluoridate-binding sites was measured from the molar ratio of bound diisopropylphosphate to protein. A value close to two binding sites was found for the C4 enzyme.
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PMID:Human-serum cholinesterase subunits and number of active sites of the major component. 100 25

Besides esterase activity, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyze o-nitroacetanilides through aryl acylamidase activity. We have reported that BuChE tetramers and monomers of human blood plasma differ in o-nitroacetanilide (ONA) hydrolysis. The homology in quaternary structure and folding of subunits in the prevalent BuChE species (G4(H)) of human plasma and AChE forms of fetal bovine serum prompted us to study the esterase and amidase activities of fetal bovine serum AChE. The k(cat)/K(m) values for acetylthiocholine (ATCh), ONA and its trifluoro derivative N-(2-nitrophenyl)-trifluoroacetamide (F-ONA) were 398 x 10(6) M(-1) min(-1), 0.8 x 10(6) M(-1) min(-1), and 17.5 x 10(6) M(-1) min(-1), respectively. The lack of inhibition of amidase activity at high F-ONA concentrations makes it unlikely that there is a role for the peripheral anionic site (PAS) in F-ONA degradation, but the inhibition of ATCh, ONA and F-ONA hydrolysis by the PAS ligand fasciculin-2 points to the transit of o-nitroacetalinides near the PAS on their way to the active site. Sedimentation analysis confirmed substrate hydrolysis by tetrameric 10.9S AChE. As compared with esterase activity, amidase activity was less sensitive to guanidine hydrochloride. This reagent led to the formation of 9.3S tetramers with partially unfolded subunits. Their capacity to hydrolyze ATCh and F-ONA revealed that, despite the conformational change, the active site architecture and functionality of AChE were partially retained.
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PMID:Hydrolysis of acetylthiocoline, o-nitroacetanilide and o-nitrotrifluoroacetanilide by fetal bovine serum acetylcholinesterase. 1929 75

Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulating of arginine and other guanidino compounds. Convulsions, lethargy and psychomotor delay or cognitive deterioration are predominant clinical features of this disease. Although neurologic symptoms predominate in this disorder, their pathophysiology is still unknown. In the present study we initially investigated the in vitro effect of arginine, homoarginine, N-acetylarginine and argininic acid on acetylcholinesterase and butyrylcholinesterase in hippocampus and serum of 15-, 30- and 60-day-old rats. Results showed that arginine in vitro significantly decreased acetylcholinesterase activity in hippocampus of 15-day-old rats and increased this enzyme activity in hippocampus of 60-day-old rats, homoarginine and N-acetylarginine significantly increased acetylcholinesterase activity both in hippocampus of 15- and 30-day-old rats. On the other hand, butyrylcholinesterase was inhibited by homoarginine in serum of 15-day-old rats. The influence of the antioxidants trolox and ascorbic acid on the effects elicited by arginine, homoarginine and N-acetylarginine was also studied. Results showed that these antioxidants were able to prevent the alteration on acetylcholinesterase and butyrylcholinesterase activities caused by guanidine compounds studied, suggesting that alterations on these cholinesterases were probably mediated by free radicals. It is presumed that these results might be associated, at least in part, with the neuronal dysfunction of patients affected by hyperargininemia.
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PMID:Guanidino compounds inhibit acetylcholinesterase and butyrylcholinesterase activities: effect neuroprotector of vitamins E plus C. 2059 4

A series of novel adamantane-substituted guanylhydrazones was synthesized and used in a study of inhibitory potential toward butyrylcholinesterase. The experimental results were further supported by using docking studies to examine the behavior of the inhibitors within the active site regions of the enzyme. The enzyme-inhibitor dissociation constants K(i) were determined from Hunter-Downs diagrams using Ellman's method for cholinesterase activity determination. Compounds 2-(N-guanidino)iminoadamantane hydrochloride (1) and 2,4-bis(N,N'-guanidino)iminoadamantane dihydrochloride (2) were found to be the best BChE inhibitors and their affinities for the enzyme active site were about five times higher compared to the enzyme peripheral site. The strongest interaction observed in complexes obtained by docking studies was the H-bond between the guanidine and the carboxylate of Glu199 and the second guanidine group in bisguanidine compounds was stabilized with additional H-bonds.
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PMID:Adamantane-substituted guanylhydrazones: novel inhibitors of butyrylcholinesterase. 2233 89