Disease relevance of BUTYRYLTHIOCHOLINE

• On the other hand, the two methods using butyrylthiocholine as substrate and that employing benzoylcholine showed limited clinical utility in discriminating subjects at risk of prolonged apnea (area under the ROC curve < or = 0.9) [1].

High impact information on BUTYRYLTHIOCHOLINE

• Site-directed mutagenesis of the conserved electronegative Glu441,Ile442,Glu443 domain to Gly441,Ile442,Gln443 drastically reduced the rate of butyrylthiocholine (BTCh) hydrolysis and caused pronounced resistance to dibucaine binding [2].
• Their mutation to leucine and valine in AcChoEase, by site-directed mutagenesis, produced a double mutant that hydrolyzed butyrylthiocholine almost as well as acetylthiocholine [3].
• Although of invertebrate origin and possessing the above substitutions in the active site gorge residues, the enzyme efficiently hydrolyzed acetylthiocholine and showed minimal activity against butyrylthiocholine [4].
• Phe-295 also determines substrate specificity in the non-covalent enzyme substrate complex and thus, the HuAChE F295A mutant exhibits over 130-fold increase in the apparent bimolecular rate constant for butyrylthiocholine compared with wild type enzyme [5].
• Each retained cholinesterase activity with butyrylthiocholine as substrate, although kcat/Km decreased 11-, 11- or 110-fold for purified G117H, E197Q, or G117H/E197Q, respectively, as compared with wild-type BChE [6].

Biological context of BUTYRYLTHIOCHOLINE

• Furthermore, the Drosophila enzyme hydrolyzed butyrylthiocholine much more efficiently than these eel or human enzymes, an indication that the fly head enzyme has a substrate specificity intermediate between mammalian acetylcholinesterases and butyrylcholinesterases [7].
• For this purpose, the kinetics of butyrylthiocholine (BTC) hydrolysis by wild-type human BuChE, by selected mutants and by horse BuChE was carried out at 25 degreeC and pH 7.0 in the presence of tetraethylammonium (TEA) [8].

Anatomical context of BUTYRYLTHIOCHOLINE

• Expressed in microinjected Xenopus laevis oocytes, the resultant chimera retained the catalytic activity, substrate specificity and the Km value toward butyrylthiocholine characteristic of BuChE [9].
• Additionally, transient expression of the cDNA in Cos-7 cells yielded extracts that exhibited cholinesterase activity and demonstrated a Km value for butyrylthiocholine of 106+/-9 nM [10].
• Butyrylcholinesterase activity in amniotic fluid was measured using butyrylthiocholine as substrate [11].
• Considering that AChE only reacts with ACh as substrate and occurs with negligible activities in the serum, the measured individual activity ratio of BChE in the serum (Q(BChE)SE) and the total hydrolysis rate of ACh and BCh in the CSF do allow a precise calculation of the AChE activity in the cerebrospinal fluid [12].
• After incubation of the muscle tissue in a medium containing butyrylthiocholine bromide as substrate and BW284c51 as the specific inhibitor of acetylcholinesterase, a distinct electron-dense precipitate corresponding to non-specific cholinesterase activity was found along the whole length of muscle spindles [13].

Associations of BUTYRYLTHIOCHOLINE with other chemical compounds

• Pseudocholinesterase (PCE) activity in oral fluid of 31 male and 24 female subjects was determined using butyrylthiocholine iodide as substrate [14].
• Comparison of the catalytic rate of aprophen hydrolysis with butyrylthiocholine (BTC) and the neutral aromatic substrate, phenylthiobutyrate (phi TB), indicated that BuChE hydrolyzed BTC and phi TB 3.2 X 10(5) and 3.1 X 10(5) times more rapidly than aprophen respectively [15].
• The alpha acetylcholinesterase showed a fairly low substrate specificity: the beta form hydrolyzed propionylthiocholine at the highest rate and was inactive on butyrylthiocholine; the gamma acetylcholinesterase, showing a marked active-site specificity with differently sized substrates, was likely functional in cholinergic synapses [16].
• The influence of ketamine upon human plasma cholinesterase (E.C. 3.1.1.8) was determined by means of a colorimetric assay technique at 25 degrees C, pH 7.7 with butyrylthiocholine as substrate [17].
• The pNPA and butyrylthiocholine hydrolysis in patient plasma was also assayed [18].

Gene context of BUTYRYLTHIOCHOLINE

• It was characterized as a true AChE since it hydrolyses acetylthiocholine more than seven times faster than butyrylthiocholine, and since it was inhibited by high concentrations of substrate [19].
• Recombinant AChE A secreted by Pichia pastoris was monomeric and hydrophilic, with a substrate preference for acetylthiocholine and negligible activity against butyrylthiocholine [20].
• Butyrylcholinesterase (pseudocholinesterase) was predominant in plasma, hydrolysing mainly butyrylthiocholine [21].
• The use of at least two substrates (acetyl and butyrylthiocholine) is recommended for whole blood cholinesterase analyses in domestic animals since it will allow monitoring of both acetyl- and butyrylcholinesterase activities, respectively, and a more accurate detection of exposure to anticholinesterase compounds [22].
• When the catalytic efficiencies are compared, soluble isoform of rat intestinal BChE became increasingly efficient as the size of the acyl portion of the substrate increases; BTCh > PTCh > ATCh [23].

References