Butyrylcholin esterase

Application of the CCM to small sets (n < 6) of enzyme inhibitors revealed correlations between the inhibitory activity and the chirality measure of the inhibitors, calculated by Eq. (26) for the entire structure or for the substructure that interacts with the enzyme (pharmacophore) [41], This was done for arylammonium inhibitors of trypsin, Di-dopamine receptor inhibitors, and organophosphate inhibitors of trypsin, acetylcholine esterase, and butyrylcholine esterase. Because the CCM values are equal for opposite enantiomers, the method had to be applied separately to the two families of enantiomers (R- and S-enantiomers). 

The choline ester is prepared by treating the 2-bromoethyl ester with trimethyl-amine. The ester is cleaved with butyrylcholine esterase (pH 6, 0.05 M phosphate buffer, rt, 50-95% yield). As with the morpholinoethyl ester, the choline ester imparts greater solubility to the C-terminal end of very hydrophobic peptides, thus improving the ability to cleave enzymatically the C-terminal ester. ... 

The classical role of AChEs is to terminate transmission of neuronal impulses by rapid hydrolysis of ACh. The closely related butyrylcholin-esterases (BuChEs) or pseudocholinesterases have a less stringent substrate specificity but their function remains ill-defined. In mammals, BuChE is found at high concentration in the plasma and the gut, where it has been... 

BUTYRYLCHOLINE ESTERASE CHOLINE SULFATASE CHOLINE SULFOTRANSFERASE CHOLOYL-OoA SYNTHETASE OHONDROITIN 4-SULFOTRANSFERASE OHONDROSULFATASES CHORISMATE MUTASE CHORISMATE SYNTHASE Chromatin self-assembly,... 

Assays of acetyl- and butyrylcholine esterases inhibition, as well as of modulation of calcium channels and nicotinic receptors have been conducted in vivo. Moreover, their interaction with the active center of acetylcholine esterase has been simulated by molecular dynamics. For synthesized compounds the IC50 of acetylcholine esterase inhibition was about 9 X M, and for the most active the value was four to five times... 

Organophosphorus compounds bearing a fluorescent group were specifically introduced into the active sites of the serine-enzymes -Chymotrypsin, Trypsin and Butyrylcholin-esterase using the agents 2, 3i and 4. This was shown using electrophoresis. 

The compounds 2, 3 and 4 are effective inhibitors of serine enzymes ( -Chymotrypsin, Trypsin, Butyrylcholin-esterase and Acetylcholin-esterase (only 4). 

Maekawa, M., K. Sudo, D.C. Dey, J. Ishikawa, M. Izumi, K. Kotani, and T. Kanno. 1997. Genetic mutations of butyrylcholine esterase identified from phenotypic abnormaUties in Japan. CUn. Chem. 43 924—929. 

OP-inhibited acetylcholinesterase and butyrylcholin-esterase are the established biomarkers of OP exposure. The special features that make them good biomarkers are ... 

This type of modified lipopeptide cannot be deblocked under basic conditions because the labile palmitic acid thioester group would be preferentially hydrolyzed. The C-terminus of the peptide chain was selectively deprotected by removing the choline ester with choline esterase without affecting the palmitic acid thioester bond. The observed chemoselectivity here is exactly opposite to that found in nonenzymatic conversions. Some of the synthesized N-terminally deprotected lipopeptides, have been labeled with biotinand are expected to serve as anchors for a protein moiety in an artificial membrane. Butyrylcholine esterase mediated cleavage of the choline ester has been utilized l as the key step in the synthesis of S-palmitoylated peptides such as Myr-Gly-Cys(Plm)-Thr-Leu-Ser-Ala-OH, which represents the characteristic N-terminus of the a-subunit of human G o protein. 

The C-terminus of a nucleopeptide choline ester 9 was deprotectedt smoothly by butyrylcholine esterase (Scheme 19). Neither the acetate, the N-terminal urethane, the allyl phosphate, the phenylacetamide and the peptide bonds, nor the acid- or base-labile purine nucleosides and serine phosphates are attacked. The methods have been exploited further for the synthesis of several biologically relevant nucleopeptides.t ... 

The solubilizing capacity of the choline residue is so pronounced that even substrates combining two hydrophobic amino acids are homogeneously soluble in aqueous buffer without any additional cosolvent. These favorable physical properties were also used in the enzymatic formation of peptide bonds. The amino acid choline ester 38 acts as the carboxyl component in kinetically controlled peptide syntheses with the amino acid amides 39 and 40 [52] (Fig. 11). The fully protected peptides 41 and 42 were built up by means of chymotrypsin in good yields. Other proteases like papain accept choline esters as substrates also, and even butyrylcholine esterase itself is able to generate peptides from these electrophiles. 

Gatley, S.J. Activities of the enantiomers of cocaine and some related compoimds as substrates and inhibitors of plasma butyrylcholin-esterase. Biochem Pharmacol 41 1249-1254, 1991. 

Laing et al. (L6) purified a bacterial cholinesterase from P. fluorescens (Goldstein strain) by fractionation on a CM Sephadex column following ammonium sulfate fractional precipitation. However, acetylcholine was the only substrate used with the purified enzyme, so that it is uncertain whether this microbiol cholinesterase is a butyrylcholine esterase or an acetylcholine esterase similar to that isolated from P. aeruginosa (T2). 

Sedimentation coefficients—Sjow—representing the velocity of sedimentation in unit gravitational field in water at 20°C, may be used, together with diffusion constants, to calculate the relative molecular masses of purified enzyme preparations. Reported values of S20W for cholinesterase isolated from human or equine serum are given in Table 7. Furthermore, the Sjow value for highly purified butyrylcholine esterase of porcine parotid gland is 9.7 units (T9) and it is 2.5 units for the enzyme from P. polycolor (N2). 

Main et al. (M5) found high concentrations of a butyrylcholine esterase, of relative molecular mass 83,000 daltons, in pooled rabbit serum. This was unexpected, since rabbit serum is classed with those mammalian sera that have low cholinesterase activities (A25, E2). Substrate specificity confirmed that the enzyme was a butyrylcholine esterase. Moreover, the active site concentration of the enzyme was five times that found for pooled horse serum, which is a rich source of the enzyme. The known fact that some rabbits can metabolize atropine, whereas others are unable to do so, can be explained by the presence or absence of serum atropinase, which is a genetic trait. Perhaps the subunit-sized butyrylcholine esterase is characteristic of some rabbits, but absent in others This seems probable according to Ellis (E9) and Koelle... 

K31), who found that benzoylcholinesterase activity varies widely among the sera of various rabbits. Unfortunately, the relevant genetics were not investigated. The presence of butyrylcholine esterase may also be questioned it acts—apparently—as a monomer in rabbit sera, but as a tetramer in human and horse sera. Perhaps the apparent absence of the tetramer and other polymers in some rabbits is the result of the inhibition or complete absence of an aggregating enzyme Does such an enzyme control the interconvertibility of the isoenzymes which are present in other plasma It is relevant that Main (private communication) isolated from rabbit liver cholinesterase two monomer forms of butyrylcholine esterase, one of which spontaneously formed a tetramer after purification. 

H23. Heilbronn, E., Hydrolysis of carboxylic acid esters of thiocholine and its analogs. III. Hydrolysis catalysed by acetylcholine esterase and butyrylcholine esterase. Acta Chem. Scand. 13, 1547-1560 (1959). 

Organophosphorus compounds are irreversible inhibitors of acetylcholine esterase and butyrylcholine esterase (BuChe, EC 3.1.1.8) because the phosphate group is irreversibly bound by the enzyme. Therefore, organophosphorus pesticides can be detected by using the free enzyme. Since the activity of cholinesterases (ChE) in normal serum is rather large (800 UA), untreated serum pools may be employed for inhibitor determination. Gruss and Scheller (1987) have shown that the hydrolysis of butyrylthiocholine iodide can be directly indicated at a membrane-covered platinum electrode polarized to +470 mV. Twenty seconds after sample addition a steady value proportional to the enzyme activity was obtained in the differentiated current-time curve. Injection of an inhibitor decreased the rate of thiocholine formation, so that the residual activity could be evaluated after 30 s (Fig. 115). 

Similarly, the respective dipeptide choline esters 34 are readily soluble in purely aqueous media (i. e. without added cosolvent) and are converted into the corresponding carboxylic acids under the mildest conditions, and without side attack on the peptide bonds and the N-terminal urethanes, by means of the commercially available butyrylcholine esterase from horse serum. The increased hydrophilicity of peptide choline esters was used advantageously used for the synthesis of peptides and very sensitive peptide conjugates such as lipidated peptides1118-1211, phosphorylated and glycosylated peptides158, 591 and nucleopeptides (Fig. 18-13)176, 781. 

Pseudocholinesterase. Acylcholine acylhydrolase. Butyrylcholine esterase. Non-specific cholinesterase. 

Butyrylcholine esterase Origin horse serum Biozyme... 

Butyrylcholine Esterase Origin horse serum Fluka... 

Blondet, B., Carpentier, G., Ferry, A., et al, 2010. Localization of butyrylcholin-esterase at the neuromuscular junction of normal and acetylcholinesterase knockout mice. J. Histochem. Cytochem. 58 (12), 1075-1082. 

Read, R.W, Riches, J.R., Stevens, J.A., et al., 2010. Biomarkers of organophosphorus nerve agent exposure comparison of phosphylated butyrylcholin-esterase and phosphylated albumin after oxime therapy. Arch. Toxicol. 84 (1), 25-36. 

Detoxification Cholinesterases enzymes hydrolyzing OP monoclonal antibodies against OP Butyrylcholin esterase. Mutants Acetylcholinesterase Triesterase Paraoxonase Very persjjective PROTEXIA ... 

Radic, Z., Pickering, N. A., Vellom, D. C., Camp, S. (1993). Palmer Taylor three distinct domains in the cholinesterase molecule confer selectivity for acetyl- and butyrylcholin-esterase inhibitors. Biochemistry 32,12074-12084. 

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