Butyrylcholine

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. ... 

Primarily hydrolyses esters with longer aliphatic (compared to AChE) or aromatic acyl moiety, such as butyrylcholine (BCh) and benzoylcholine (BzCh). BChE is the primary circulating ChE. It is threefold more abundant than AChE in human blood and is found in liver, lungs, muscles, brain and heart. 

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... 

There is some confusion in the literature regarding the substances designated as anti-choline-esterases (usually shortened to anticholinesterases). The term cholinesterase was first used1 in connexion with an enzyme present in the blood serum of the horse which catalysed the hydrolysis of acetylcholine and of butyrylcholine, but exhibited little activity towards methyl butyrate,... 

Thus a distinction was provided between simple esterases, such as fiver esterase, which catalysed the hydrolysis of simple aliphatic esters but were ineffective towards choline esters. The term 1 cholinesterase was extended to other enzymes, present in blood sera and erythrocytes of other animals, including man, and in nervous tissue, which catalysed the hydrolysis of acetylcholine. It was assumed that only one enzyme was involved until Alles and Hawes2 found that the enzyme present in human erythrocytes readily catalysed the hydrolysis of acetylcholine, but was inactive towards butyrylcholine. Human-serum enzyme, on the other hand, hydrolyses butyrylcholine more rapidly than acetylcholine. The erythrocyte enzyme is sometimes called true cholinesterase, whereas the serum enzyme is sometimes called pseudo-cholinesterase. Stedman,3 however, prefers the names a-cholinesterase for the enzyme more active towards acetylcholine, and / -cholinesterase for the one preferentially hydrolysing butyrylcholine. Enzymes of the first type play a fundamental part in acetylcholine metabolism in vivo. The function of the second type in vivo is obscure. Not everyone agrees with the designation suggested by Stedman. It must also be stressed that enzymes of one type from different species are not always identical in every respect.4 Furthermore,... 

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... 

Acetylcholine is the optimal substrate for acetylcholinesterase, whereas butyrylcholine is the optimal substrate for butyrylcholinesterase. 80,104 Acetylcholinesterase does not hydrolyze butyrylcholine very efficiently-... 

Mesulam M, Guillozet A, Shaw P, et al Widely spread butyrylcholines-terase can hydrolyze acetylcholine in the normal and Alzheimer brain. Neurobiol Dis 9 88-93, 2002... 

The more widely distributed butyrylcholinesterase612 is less specific but prefers butyrylcholine. Acetylcholinesterase is a very efficient catalyst 613-615 /ccat = 1.6 x 104 s-1... 

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). 

Acetylcholineesterase and choline oxidase Amniotic fluid was mixed at 27° C with phosphate buffer (pH 8) and the current was measured with an electrode consisting of an immobilized choline oxidase membrane at 650 mV versus Ag/AgCl. After reaching the steady state, acetylcholine or butyrylcholine was added and the current was measured. Rapid and sensitive discriminating determination of AChE activity in amniotic fluid with choline sensor. The calibration graphs were rectilinear and the coefficient of variation was 2.5%. [116]... 

Butyrylcholine iodide monohydrate (Calbiochem grade B) was used as the substrate for plasma assay, and the results are expressed as micromoles of butyric acid produced per milliliter of plasma per minute. 

This name reflects that the activity of this enzyme used to be assayed with butyrylcholine (Tm not sure if that model substrate is still in use). However, the enzyme also cleaves acetylcholine and many other natural or synthetic choline esters, just as p-galactosidase cleaves both lactose and many synthetic 3-galactosides, including the blue X-Gal that you may have seen in the lab. 

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 ... 

Scheme 19 Selective Deprotection of the C-Terminus of a Nucleopeptide Choline Ester by Butyrylcholine Esteraseb l...

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