Acetylcholinesterase genetic variants

Pharmacokinetics Succinylcholine is composed of two acetylcholine molecules linked end to end. Succinylcholine is metabolized by plasma cholinesterase (butyrylcholinesterase or pseudocholinesterase), which determines the amount of drug reaching the end plate. It has a duration of action of only a few minutes if given as a single dose. Blockade may be prolonged in patients with genetic variants of plasma cholinesterase that metabolize succinylcholine very slowly. Succinylcholine is not rapidly hydrolyzed by acetylcholinesterase. 

Other metabolic enzymes that show polymorphic differences in that they can occur as genetic high-activity and low-activity variants include acetylcholinesterase, butyrylcholinesterases, flavin-dependent monooxygenase, alcohol dehydrogenase, epoxide hydrolase, and arylesterase (Beltoft et al. 2001). 

Many individuals have genetic susceptibility to certain chemicals (Calabrese 1978). The influence of these genetic differences likely produces sub- and supersensitivity to OP insecticides and warfare agents (Russell and Overstreet 1987). Several enzymes with variations or polymorphisms control sensitivity to OPs red blood cell acetylcholinesterase, serum cholinesterase or pseudocholinesterase, lymphocyte neuropathy target esterase or platelet neuropathy target esterase (NTE), serum paroxonase, butyrylcholinesterase, and serum arylesterase (Costa et al. 1999 LaDu 1988 Li et al. 1993 Mutch et al. 1992). Inhibition of red blood cell acetylcholinesterase, in both the central and the peripheral nervous systems, produces acute symptoms (Mutch et al. 1992). Paroxonase and arylesterase further modify the response (LaDu 1988 Li et al. 1993). Variant, inactive butyrylcho-linesterases increase sensitivity to OPs (Lockridge and Masson 2000 Schwarz et al. 1995). OP-induced delayed polyneuropathy results... 

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