Plasma BuChEs

Substrate preferences for AChEs and BuChEs vary with the species. Both mammal and bird AChEs rapidly hydrolyze ACh and its thiocholine analog acetylthiocholine (AcTh) (Silver 1974). Plasma-BuChE activity in the rat is reported to favor propionyl rather than butyryl substrates (Augustinsson 1948 Hoffmann et al. 1989). AChEs and BuChEs respond differently to increasing substrate concentration. AChEs are inhibited by excess substrate above 1-2 millimolars (mM) (Wilson et al. 1997 Silver 1974). BuChEs are less sensitive. BuChEs are preferentially inhibited by the selective inhibitor iso-OMPA and quinidine, and AChEs by the bisquatemary compound BW284c51. 

For practical purposes (individual and interindividual variation), determination of individual norm activity is recommended (this approach is better than that of calculating the decrease from an average value) as well as separate determination of cholinesterases, the red blood cell AChE and plasma BuChE. The activity determined in the whole human blood corresponds to about 10% of BuChE and 90% of AChE. This is different to rats where this ratio is 29% of BuChE and 71% of AChE (Bajgar, 1972). Erythrocyte AChE activity seems to be more useful for these purposes than BuChE activity in plasma. 

For the purposes of occupational medicine, the determination of cholinesterases in the blood of workers intoxicated with OP is obhgatory. However, the normal values varied within the laboratories depending on the method of determination. Systematic monitoring of workers with nerve agents was performed at our department from 1962 to 1963 however, the results presented contain determinations during 40 years (1964-2004). Because of the large number of results, the results are limited to RBC AChE only although plasma BuChE aetivity was also determined. 

In a practical way, the best appreciation of cholinesterase was performed using individual norms for RBC AChE. It seems to be the most sensitive parameter for monitoring cholinesterase changes in exposed workers, followed by a sensitivity for whole blood hemolysate. Plasma BuChE activity is not so specific and is a sensitive parameter. A decrease of 30% of individual norms seems to be critical for further consideration. In conclusion, cholinesterase determination in blood (especially RBC AChE) is a good parameter for monitoring and laboratory examination of... 

Navratil, L., Bajgar, J. (1987). Relationship between plasma BuChE activity total cholesterolaemia. Biochem. Clin. Bohemoslov. 16 117-21. (In Czech)... 

An example may illustrate how sensitive plasma BuChE is to inhibition. Rats dosed orally with bromophos needed only 10.1 mg/kg of body weight for the enzyme activity to be reduced to half, whereas the erythrocyte AChE I50 was 1938 mg/kg and the brain AChE I50 was 576 mg/kg. The plasma 150 dose did not give any symptoms of poisoning (oral LD50 for rats = 3750 to 7700 mg/kg). It is very clear that plasma enzymes may be inhibited at much lower concentrations than needed to give the more severe symptoms associated with AChE inhibition in the nervous system, and they can be used in early-warning monitoring (Shivanandappa et al., 1988). 

FIG. 13, (A) Plasma time course of diazinon (DZN), (B) plasma BuChE inhibition, and (C) pla.sma AChE inhibition in rats following oral administration of 50 (gray) or 100 (black) mg DZN/kg of body weight, respectively. The linc.s represent the model simulation of the experimental data. Adapted with permission from Poet et al. (2004). 

AChE activity in human blood reflects the activity of synaptic AChE, which i.s the target enzyme of anticholinestera.scs. However, many OFs or CMs Inhibit plasma BuChE faster than erythrocyte AChE, and the inhibition of pla,sma BuChE is for those compound.s a more. sensitive indicator of absorption. Con.scquently, more infonnation about the exposure of an individual to OPs or CMs can be obtained if both AChE and BuChE are measured. 

Although erythrocyte cholinesterase is invariably more specific than BuChE activity as a marker of OP insecticide exposure, some OP insecticides (c,g,. chlorpyrifos, deme-lon, and malathion) depress plasma BuChE activity to a greater degree. 

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