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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans and trans-trans) undergo rapid metabolism by plasma cholinesterase (t1/2 beta < 2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5-10% of control T1 amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg.kg-1 (Group EDR-1), 0.25 mg.kg-1 (Group EDR-2), or 0.50 mg.kg-1 (Group EDR-3), in addition to a corresponding dose of atropine. Spontaneous recovery, from a T1 response of < 10% to a TOF ratio > or = 0.7, required 13.5 +/- 2.6 min (PLAC Group). In comparison, patients in the EDR-1 group required 9.2 +/- 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of > or = 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an EUEA genotype, whereas the two patients with delayed recovery in the EDR-1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg.kg-1) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg.kg-1 provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.
...
PMID:Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium. 859 May 11

We have compared the reversal characteristics of mivacurium after administration of an edrophonium-plasma cholinesterase (PCHE) combination with that produced by each antagonist alone. Forty ASA I adults were given mivacurium 0.15 mg kg-1 during fentanyl-thiopentone-nitrous oxide-isoflurane anaesthesia. TOF stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height (T1) reached 10% of its initial control value, patients were allocated randomly to one of four groups (n = 10 in each). Neuromuscular function in patients in group 1 (control group) was allowed to recover spontaneously. Patients in groups 2-4, respectively, received edrophonium 1 mg kg-1 (group ED), exogenous PCHE equivalent to activity present in 25 ml kg-1 of human plasma (group PCHE) or edrophonium 1 mg kg-1 with exogenous human PCHE equivalent to the activity present in 25 ml kg-1 of human plasma (combination group). The time to attain a TOF ratio of 0.75 in the combination group was 4.6 (SD 0.9) min. This was shorter (P < 0.01) than that observed in patients in the control (16.8 (3.3) min), ED (8.9 (3.6) min) and PCHE (9.3 (1.6) min) groups. There was no difference in recovery indices between groups ED and PCHE. We have demonstrated that the edrophonium-PCHE combination significantly accelerated recovery of mivacurium-induced block compared with that observed with the use of individual antagonists.
...
PMID:Edrophonium and human plasma cholinesterase combination for antagonism of mivacurium-induced neuromuscular block. 894 25

Mivacurium is metabolized by plasma cholinesterase (PCHE). Metoclopramide inhibits PCHE in vitro and in vivo. We have assessed the effect of metoclopramide on duration of action of mivacurium and measured PCHE at baseline and at the time of maximal block. In a randomized, double-blind study, 30 patients received metoclopramide 0.15 mg kg-1 i.v. or saline, followed by propofol anaesthesia and mivacurium 0.15 mg kg-1. Using a TOF-Guard accelerometer, times to recovery of TI to 25%, 75% and 90% were 13.4, 19.3 and 21.9 min in the saline group and 17.8, 25.3 and 28.8 min in the metoclopramide group (P < 0.01, P < 0.05, P < 0.05, respectively). There were no differences in onset time or recovery index between the groups. PCHE activity at the time of maximum block decreased within each group (P < 0.01) but there was no difference between groups. In a second biochemical study of eight patients, a small decrease in PCHE activity was detected after metoclopramide 0.15 mg kg-1, but before administration of mivacurium (P < 0.025). We conclude that metoclopramide prolongs the duration of action of mivacurium.
...
PMID:Influence of metoclopramide on plasma cholinesterase and duration of action of mivacurium. 1047 19

Previous kinetic studies found that butyrylcholinesterase (BChE) inhibited by (1R)-isomalathions readily reactivated, while enzyme inactivated by (1S)-isomers did not. This study tested the hypothesis that (1R)- and (1S)-isomers inhibit BChE by different mechanisms, yielding distinct adducts identifiable by peptide mass mapping with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Equine BChE (EBChE) was inhibited to <10% of control activity with each isomer of isomalathion and the reference compound isoparathion methyl. Control and treated enzyme was digested with trypsin, and peptides were fractionated with HPLC. Separated and unseparated peptides were analyzed with MALDI-TOF-MS. Identity of an organophosphorus peptide adduct was confirmed by fragmentation using postsource decay analysis. EBChE inhibited by (1R)-isomalathions or (S)-isoparathion methyl readily reactivated after oxime treatment with 30-40% activity recovered. Enzyme inactivated by (1S)-isomalathions or (R)-isoparathion methyl recovered <2% and <5% activity, respectively, after oxime treatment. MALDI-TOF-MS analysis revealed that inhibition of EBChE by (1R)-isomalathions and (R)- or (S)-isoparathion methyl yielded O,S-dimethyl phosphate adducts. Enzyme inactivated by (1S)-isomalathions produced only O-methyl phosphate adduct. EBChE modified by (1R)-isomalathions or either enantiomer of isoparathion methyl yielded an O-methyl phosphate adduct as well. The results indicate that EBChE inhibition by (1R)-isomalathions proceeds with loss of diethyl thiosuccinate, but inactivation by (1S)-isomers occurs with loss of thiomethyl as the primary leaving group followed by rapid expulsion of diethyl thiosuccinate to yield an aged enzyme. Furthermore, the data suggest that aging of the O,S-dimethyl phosphate adduct occurs via an S(N)2 process with loss of thiomethyl.
...
PMID:Identification of butyrylcholinesterase adducts after inhibition with isomalathion using mass spectrometry: difference in mechanism between (1R)- and (1S)-stereoisomers. 1160 83

A novel, proteomics based method was developed for the detection, quantification, and categorization of serum butyrylcholinesterase (BChE) inhibitors, including organophosphates (OPs) and carbamates (CBs). This method was based on the MALDI-TOF-MS analysis of the trypsin generated BChE active site peptide (191-SVTLFGESAGAASVSLHLLSPR-212) previously modified by reaction with an OP or CB. The ionization efficiency of OP modified active site peptides by MALDI was greatly improved by adding diammonium citrate to the MALDI matrix, which made the quantification of OP exposure feasible. Excellent linearity (r2 > 0.98) between the normalized abundance ratios (NARs) and OP concentrations or logarithm of carbaryl concentration was obtained. The accuracy of the developed assay was evaluated by comparison of IC50 and IC100 values from the assay with those determined by the Ellman method. Results from this method were comparable with those from the Ellman method. The advantage of the assay was that both the origin and the extent of pesticide exposure can be determined in one analysis. Our MALDI method can provide critical evidence for the pesticide exposure at low BChE inhibition levels even down to 3%, not available with the Ellman method.
...
PMID:Development of a MALDI-TOF-MS method to identify and quantify butyrylcholinesterase inhibition resulting from exposure to organophosphate and carbamate pesticides. 1722 55

An analysis method for determining isopropyl methylphosphonic acid (IMPA) and cyclohexyl methylphosphonic acid (CMPA), the metabolic hydrolysis products of toxic organophosphorus nerve agents isopropyl methylphosphonofluoridate (sarin, GB) and cyclohexyl methylphosphonofluoridate (cyclosarin, GF), respectively, has been developed and validated using high-performance liquid chromatography-mass spectrometry with negative ion electrospray ionization with time-of-flight detection (LC-ESI-MS-TOF). The linear range of quantitation was 5 to 125 ng/mL in plasma with a method detection limit of 2 ng/mL for each compound. This method was developed to determine the amount of metabolic hydrolysis that was formed during and after nerve agent exposure in minipigs to account for a major pathway of GB and GF elimination that had not been previously characterized in the bloodstream, particularly during low-level whole-body inhalation experiments. Metabolic hydrolysis accounted for 70% to 90% of the recoverable agent in the bloodstream during exposure, when compared to both unbound and cholinesterase bound agent recovered by fluoride ion reactivation analysis for the same samples. The estimated half-life of IMPA and CMPA in plasma was determined to be 44 and 61 min, respectively. The method utilizes the mass selectivity of LC-ESI-MS-TOF using a bench-top instrument to achieve a detection limit that is consistent with reported LC-MS-MS methods analyzing blood samples.
...
PMID:Quantification of sarin and cyclosarin metabolites isopropyl methylphosphonic acid and cyclohexyl methylphosphonic acid in minipig plasma using isotope-dilution and liquid chromatography- time-of-flight mass spectrometry. 1826 98

A novel toxic polypeptide, INN-toxin, is purified from the venom of Naja naja using combination of gel-permeation and ion-exchange chromatography. It has a molecular mass of 6951.6Da as determined by MALDI-TOF/MS and the N-terminal sequence of LKXNKLVPLF. It showed both neurotoxic as well as cytotoxic activities. INN-toxin is lethal to mice with a LD(50) of 1.2mg/kg body weight. IgY raised in chicks against basic peptide pool neutralized the toxicity of INN-toxin. INN-toxin did not inhibit cholinesterase activity. It is toxic to Ehrlich ascites tumor (EAT) cells, but it is not toxic to leukocyte culture. The toxin appears to be specific in its mode of action. Interaction of N-bromosuccinamide (NBS) with the peptide resulted in the modification of tryptophan residues and loss of lethal toxicity of INN-toxin.
...
PMID:INN-toxin, a highly lethal peptide from the venom of Indian cobra (Naja naja) venom-Isolation, characterization and pharmacological actions. 1876 Mar 17

The goal was to test 14 nerve agent model compounds of soman, sarin, tabun, and cyclohexyl methylphosphonofluoridate (GF) for their suitability as substitutes for true nerve agents. We wanted to know whether the model compounds would form the identical covalent adduct with human butyrylcholinesterase that is produced by reaction with true nerve agents. Nerve agent model compounds containing thiocholine or thiomethyl in place of fluorine or cyanide were synthesized as Sp and Rp stereoisomers. Purified human butyrylcholinesterase was treated with a 45-fold molar excess of nerve agent analogue at pH 7.4 for 17 h at 21 degrees C. The protein was denatured by boiling and was digested with trypsin. Aged and nonaged active site peptide adducts were quantified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of the tryptic digest mixture. The active site peptides were isolated by HPLC and analyzed by MALDI-TOF-TOF mass spectrometry. Serine 198 of butyrylcholinesterase was covalently modified by all 14 compounds. Thiocholine was the leaving group in all compounds that had thiocholine in place of fluorine or cyanide. Thiomethyl was the leaving group in the GF thiomethyl compounds. However, sarin thiomethyl compounds released either thiomethyl or isopropyl, while soman thiomethyl compounds released either thiomethyl or pinacolyl. Thiocholine compounds reacted more rapidly with butyrylcholinesterase than thiomethyl compounds. Labeling with the model compounds resulted in aged adducts that had lost the O-alkyl group (O-ethyl for tabun, O-cyclohexyl for GF, isopropyl for sarin, and pinacolyl for soman) in addition to the thiocholine or thiomethyl group. The nerve agent model compounds containing thiocholine and the GF thiomethyl analogue were found to be suitable substitutes for true soman, sarin, tabun, and GF in terms of the adduct that they produced with human butyrylcholinesterase. However, the soman and sarin thiomethyl compounds yielded two types of adducts, one of which was thiomethyl phosphonate, a modification not found after treatment with authentic soman and sarin.
...
PMID:Nerve agent analogues that produce authentic soman, sarin, tabun, and cyclohexyl methylphosphonate-modified human butyrylcholinesterase. 1971 48

The aspirin esterase activity of human plasma is due to butyrylcholinesterase and albumin. Our goal was to identify the amino acid residues involved in the aspirin esterase activity of albumin. Fatty acid-free human albumin and human plasma were treated with aspirin for 5 min-24 h. Acetylated residues were identified by LC/MS/MS and MALDI-TOF/TOF mass spectrometry of tryptic peptides. Treatment with 0.3 mM aspirin resulted in acetylation of Lys-199, Lys-402, Lys-519, and Lys-545. Treatment with 20 mM aspirin resulted in acetylation of 26 lysines. There was no acetylation of Tyr-411, under any conditions. Acetylated lysine was stable for at least 21 days at pH 7.4, 37 degrees C. Albumin acetylated by aspirin had reduced esterase activity with beta-naphthyl acetate as shown on gels stained for esterase activity. It was concluded that the aspirin esterase activity of albumin is a pseudo-esterase activity in which aspirin stably acetylates lysines and releases salicylate.
...
PMID:Reaction of human albumin with aspirin in vitro: mass spectrometric identification of acetylated lysines 199, 402, 519, and 545. 1983 60

N-trans-p-coumaroyltyramine (CT) isolated from Physalis minima is a phenolic substance exhibiting many pharmacological activities like potent inhibition of acetyl cholinesterase, cell proliferation, platelet aggregation, and also antioxidant activity. Here, we have studied the binding of CT with HSA at physiological pH 7.2 by using fluorescence, circular dichroism spectroscopy, mass spectrometry, and molecular docking methods. From the fluorescence emission studies, the number of binding sites and binding constant were calculated to be 2 and (4.5 +/- 0.01) x 10(5) M(-1), respectively. The free energy change was calculated as -7.6 kcal M(-1) at 25 degrees C, which indicates the hydrophobic interactions of CT with HSA and is in well agreement with the computational calculations and molecular docking studies. The changes in the secondary structure of HSA after its complexation with the ligand were studied with CD spectroscopy, which indicated that the protein became partially unfolded. Also, temperature did not affect the HSA-CT complexes. The binding of CT with HSA was detected as 2 molecules bound to HSA was determined using micro TOF-Q mass spectrometry. Further, molecular docking studies revealed that CT was binding at subdomain IIA with hydrophobic interactions and also by hydrogen-bond interactions between the hydroxyl (OH) group of carbon-16 and carbon-2 of CT and Arg222, Ala291, Val293, and Met298 of HSA, with hydrogen-bond distances of 2.488, 2.811, 2.678, and 2.586 A, respectively.
...
PMID:Interaction studies of coumaroyltyramine with human serum albumin and its biological importance. 2013 5


1 2 3 Next >>

---