Human butyryl cholinesterase

Raveh, L., Grauer, E., Grunwald, J., Cohen, E., and Ashani, Y., The stoichiometry of protection against soman and VX toxicity in monkeys pretreated with human butyryl-cholinesterase, Toxicol. Appl. Pharmacol, 145, 43, 1997. 

FIGURE 7.3 Comparative reactivation kinetics of soman-inhibited human butyryl-cholinesterase single mutant G117H ( ) and double mutant G117H/E197Q ( ). Note that the recovery rate of the double mutant is very fast (with reaction rates of 77,000 and 128,000 per minute for the PgCj and PgC isomers of soman, respectively), while the single mutant does not recover measurably. The insert shows that reactivation of the double mutant with soman can be treated as a first-order reaction for at least 2.5 X lO s. 

LC-MS is a powerful method used to detect and quantify CWAs. The use of LC-MS for CWA and hydrolysis product detection has been reviewed [7,20,26]. LC-MS methods are often used to detect CWA hydrolysis/ degradation products instead of the active agents [27-28]. LC-MS serves as a bioanalytical method for CWA detection in living systems and its contributions have also been reviewed [7, 26, 29]. A LC-MS method using an on-line trypsin digestion is used to identify GB and sulfur mustard adducts with proteins and enzymes like human butyryl cholinesterase [30]. This technique, along with similar techniques, could be applied to confirm CWA exposure when illness is suspected from an unknown toxin. 

Nachon, R, Carletti, E., Wandhammer, M., et al, 2011. X-ray crystallographic snapshots of reaction intermediates in the G117H mutant of human butyryl-cholinesterase, a nerve agent target engineered into a catalytic bioscavenger. Biochem. J. 434, 73-82. 

Noort, D., Fidder, A., Van der Schans, M.J., et al., 2006. Verification of exposure to OPs generic mass spectrometric method for detection of human butyryl-cholinesterase adducts. Anal. Chem. 78,6640-6644. 

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-... 

Fig. 8. Terrapin bioprofiling pattern (adapted from ref. 47). Al, human gluthathione-5-transferase R8, rat glutathione-S-tranferase SI, schistosome glu-tathione-5-transferase HF2, housefly glutathione-i -transferase DAO, porcine D-amino acid oxidase BCh, equine butyryl cholinesterase Pap, papain PDE, snake venom phosphodiesterase I.

Simeon-Rudolf, V., and Evans, R. T. (2001). Imcrlaboratory study into the proficiency of attribution of human scrum butyryl-cholinesterase phenotypes Reference values of activitie.s and inhibitor numbers. Acta Pharm. 51,289-296. 

Allon, N., L. Raveh, E. Gilat, E. Cohen, J. Grunwald, and Y. Ashani. 1998. Prophylaxis against soman inhalation toxicity in guineapigs by pretreatment alone with human serum butyryl-cholinesterase. Toxicol. Sci. 43(2) 121-28. 

Nachon, R, Carletti, E., Ronco, C, et al., 2013. Crystal structures of human cholinesterases in complex with huprine W and tacrine elements of specificity for anti-Alzheimer s drugs targeting acetyl- and butyryl-cholinesterase. J. 

At high substrate concentrations, neither human nor horse plasma cholinesterase shows substrate inhibition with either acetyl- or butyryl-choline, but substrate inhibition is observed with halogenoacetylcholines... 

Differences between the species toward the thiocholine substrates have been reported. Table 11.1 illustrates some observed differences with three species. For plasma pseudocholinesterase measurements, dog, rabbit, and man show higher substrate specificity for butyryl substrates, whereas rat, mouse, and hamster show higher specihcity for propionyl substrates all the species show less specihcity toward benzoyl substrates. Female rats have higher values compared to males with all three substrates, and the cholinesterase levels in platelets are higher in rats compared to the very low levels in human platelets. 

---