Pseudocholinesterase, polymorphism

Pseudocholinesterase is a polymorphic enzyme. Succinylcholine is a paralyzing agent used during surgery to prevent muscle twitching. When succinylcholine is used in patients who are deficient in pseudocholinesterase, they wake up from the anesthetic but remain paralyzed for a prolonged period of time. 

Mutations that cause a disease are rare and often lead to early death. Genetic poly-tnorphism are more common and are officially defined as occurring in more than l%of the population. Some of the clinically important polymorphisms associated with metabolism enzymes include CYP2C9, CYP2D6, CYP2C19, FMO, plasma pseudocholinesterase, N-acetyltransferase, thiopurine methyl-transferase, and UDP-glucuronysyltrans-ferase (107-113). 

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... 

There are two main enzymes of interest. Acetylcholinesterase (AChE EC 3.1.1.7) has an affinity for the substrate acetylcholine and it is found in the erythrocytes and nervous tissue. The enzyme is sometimes referred to as true cholinesterase, and it exists in differing polymorphic forms (Skau 1985). Butyrylcholinesterase (BuChE, acylcholine acylhydrolase, EC 3.1.1.8)—also known as pseudocholinesterase or nonspecific cholinesterase— has affinities for the substrates butyrylcholine and/or pro-pionylcholine, which are dependent on the animal species (Myers 1953 Ecobichon and Comeau 1973 Scarsella et al. 1979 Unakami et al. 1987 Evans 1990 Matthew and Chapin 1990 Woodard et al. 1994). 

Genetic polymorphism exists with pseudocholinesterases ° Example local anesthetics Monoamine oxidases... 

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