Butyryl-cholinesterase

Atta-ur-Rahman, Parveen, S., Khalid, A., Farooq, A., and Choudhary, M.I. (2001). Acetyl and butyryl cholinesterase -inhibiting triterpenoid alkaloids from Buxus papillosa. Phytochemistry 58 963-968. 

Released ACh is rapidly hydrolyzed and inactivated by a specific acetylcholinesterase, present on pre- and postjunctional membranes, or by a less specific serum cholinesterase (butyryl cholinesterase), a soluble enzyme present in serum and interstitial fluid. 

Blood pressure effect. Fruit juice, administered intravenously hy infusion to dogs at a dose of 3 mL/minute for 100 minutes, was active. Initial effect was a decrease in hlood pressure . Oil, administered to male weanling rats at a dose of 10% of diet for 5 weeks, produced significantly higher hlood pressure than other groups. Systolic hlood pressure was found related to the dietary intakes of saturated and unsaturated fatty acids. Prenatal exposure of the rats to a maternal low-protein diet abolished the hypertensive effect of the coconut oil dieH . Butyryl cholinesterase activity. Oil was administered to rats at different doses with or without clofibrate for 15 days. The hypolipidemic action of clofibrate was not... 

CNIOI Van Lith, H. A., M. Haller, G. Van Tintelen, A. G. Lemmens, L. E. Van Zutphen, and A. C. Beynen. Eat intake and clofibrate administration have interrelated effects on liver cholesterol concentration and serum butyryl cholinesterase activity in rats. J Nutr 1992 122(11) 2283-2291. 

Enzymes inhibited Acetylcholinesterase (AChE) AChE, butyryl-cholinesterase (BuChE) AChE... 

Fig. 28.3. Reproduced from Fig. 3 of Ref. [45], with permission from Elsevier. Detection of organo-phosphates extracted from wool, (a) Extracts containing either chlorfenvinphos (C) or diazinon (D) numbers are X in 10-XM. (b) Extracts containing mixtures of the two total concentration of organo-phosphates was 10-5M. Electrodes were exposed to the extracts, dried overnight and the currents generated in the presence of butyrylthiocholine measured. White columns, electric eel acetylcholinesterase grey, bovine erythrocyte acetylcholinesterase and black, horse serum butyryl cholinesterase.

We have described a protocol for the use of butyryl cholinesterase but it is also possible to use cholinesterases from other sources... 

The acetylcholine, in turn, is hydrolyzed by both acetylcholinesterase and plasma butyryl-cholinesterase. Choline is actively transported into nerve terminals (synaptosomes) by a high-affinity uptake mechanism. Furthermore, the availability of choline regulates the synthesis of acetylcholine (Figure 14.4). 

Tacrine is a non-competitive, irreversible inhibitor of both acetyl and butyryl cholinesterase, with a greater potency for the latter enzyme. Based on the outcome of placebo-controlled, double-blind studies, tacrine was the first anticholinesterase to be licensed for the symptomatic treatment of AD in the United States. The main disadvantage of tacrine lies in its hepatotoxicity (approximately 50% of patients were found to develop elevated liver transaminases which reversed on discontinuation of the drug). Because of such side effects and limited efficacy, tacrine is no longer widely prescribed. 

Rivastigmine is a pseudo-irreversible inhibitor of both acetyl and butyryl cholinesterases. Thus although the drug initially blocks the enzymes, it is metabolized by them thereby giving the drug a relatively short half-life. The top dose is often necessary to achieve therapeutic efficacy, at which dose the central and peripheral cholinergic side effects become apparent. 

Galantamine, unlike the other anticholinesterases in clinical use, is derived from the alkaloids from the daffodil and snowdrop family. It is a reversible, competitive inhibitor of acetylcholinesterase with some inhibitory action on butyryl cholinesterase. It is also an agonist at nicotinic receptor sites. Although a clinically effective drug, galantamine frequently causes gastrointestinal side effects. 

TMS derivative by GC/FPD in urine collected over 7 days from casualties of the Tokyo attack (43). Concentrations were not reported but the estimated exposures were 0.13-0.25 mg of sarin in a comatose patient and 0.016-0.032 mg in less severely intoxicated patients. Using LC/MS/MS and a more rigorous method of quantitation, /-PrMPA was detected underivatized in serum at concentrations of 3-136ng/ml in four casualties of the Matsumoto incident and 2-100ng/ml in 13 casualties of the Tokyo attack (59). All samples were taken within 2.5 hours of hospitalization. High levels of /-PrMPA correlated with low levels of butyryl-cholinesterase activity. Other positive analyses associated with these incidents were obtained by identification of inhibited cholinesterase, and are reported in Part B. 

Yu Q, et al. Synthesis of novel phenser-ine-based-selective inhibitors of butyryl-cholinesterase for Alzheimer s disease. /. Med. Chem., 1999, 42(10), 1855-1861. 

Acetylcholinesterase (AChE), Butyryl-cholinesterase (BChE) Alkaloid... 

BBB, blood brain barrier BBI, Bowman-Birk serine protease inhibitor BB-R, bombesin receptor BChE, butyryl cholinesterase BDNF, brain-derived neurotrophic factor BDNF-RTK, brain-derived neurotrophic factor receptor tyrosine kinase aBgTX, a-bungarotoxin BKAS, (3-ketoacyl-ACP synthase BK-R, bradykinin receptor BZ-R, benzodiazepine receptor... 

In contrast to acetylcholinesterase, which is selective for acetylcholine, butyryl-cholinesterase tolerates a wider variety of esters and is more active with butyryl-and propionylcholines than acetylcholine [7]. Structure-activity relationship studies have shown that different steric restrictions in the acyl pockets of AChE and BChE cause the difference in specificity to the acyl moiety of the substrate [6]. 

Succinylcholine has a more sustained action at the motor endplate than acetylcholine has because it is insensitive to the acetylcholinesterase found in the S5uiapse. There is, however, a second variety of cholinesterase that circulates in the blood plasma, also referred to as butyryl-cholinesterase, which cleaves succinylcholine within minutes. This moderately rapid inactivation makes it possible to control the degree of muscle relaxation by adjusting the infusion rate of the agent after discontinuation, the remaining succinylcholine will be swiftly hydrolysed, and the block will subside ... 

Most hospitals and forensic laboratories are capable of performing cholinesterase activity assays. Two examples of the usefulness of acetylcholinesterase and butyryl-cholinesterase activity assays are given below. 

In keeping with the concept of the RIP discussed under Relative Inhibitory Potency , above, inhibition of lymphocyte and/or platelet NTE and possibly erythrocyte LysoPC hydrolase should be used in conjunction with inhibition of erythrocyte AChE and plasma butyryl-cholinesterase (BChE) to assess the likelihood that an exposure to OP compounds would produce cholinergic and/ or delayed neuropathic effects. Erythrocyte AChE inhibition has long been used as a biomarker of exposure to conventional nerve agents or OP insecticides (Lotti, 1995 Wilson and Henderson, 1992). BChE can be sensitive to both conventional and DN agents, and its inhibition could thus serve as a general biomarker for OP agents (Kropp and Richardson, 2007 Van der Schans et al, 2008). 

Acetyl-chohnesterases (AChE, EC 3.1.1.7, also called true cholinesterase) and acylcholine acylhydrolases (or pseudocholinesterases including butyryl-cholinesterase, BuChE, EC 3.1.1.8) are commercially available enz5mies from different biological sources that catalyse the hydrolysis of acetyl- or butyryl-choline into choline and acetate or butyrate, respectively, according to the following reaction ... 

Carboxylesterase from the liver, butyryl cholinesterase and acetyl cholinesterase from erythrocytes do not interfere with analysis, i.e. they do not exercise any activity in respect of the substrate. Contamination of the sample by glycerol, soap and hand cream must be avoided. 

N-Acety I transferase3 Alcohol dehydrogenase3 Aldehyde dehydrogenase3 Butyryl cholinesterase Catalase... 

Several members of a series of hybrid molecules of THA and huperzine-A (279) were more active against acetylcholinesterase than (-)-huperzine-A,but they were not as selective for the enzyme (compared with butyryl-cholinesterase) as huperzine-A (349). Molecular modeling of compounds in the series with acetylcholinesterase from Torpedo californica showed them to interact "as truly THA-huper-zine-A hybrids." However, it was noted that acetylcholinesterase from Torpedo is somewhat different from that of humans. A subsequent paper (350) reported a study of predic-... 

Ibrahim et al. [182] isolated four sesquiterpene lactones from the ethyl acetate soluble fraction of Amberboa ramosa. One compound, Amberbin C, was found to be new while other three compounds, Amberin, Amberbin A, and Amberbin B, were previously reported. All compounds showed inhibitory activities against acetyl cholinesterase and butyryl cholinesterase. 

Ibrahim M, Farooq T, Hussain N, Hussain A, Gulzar T, Hussain I et al (2013) Acetyl and butyryl cholinesterase inhibitory sesquiterpene lactones from Amberboa ramosa. Chem Cent J 7 116... 

Ashani, Y., Shapira, S., Levy, D., Wolfe, A. D., Doctor, B. P., Raveh, L. (1991). Butyryl-cholinesterase and acetylcholinesterase prophylaxis against soman poisoning in mice. Biochemical Pharmacology, 41, 37—11. 

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