Dibucaine-resistant variant

Most clear-cut and usually without ambiguity is the identification of subjects who have only the atypical, dibucaine-resistant variant in their plasma—that is, subjects who are either homozygous for at3q>ical esterase (EjEj) or heterozygous with one silent gene and one for at q>ical esterase (E-Et). 

M21. Muensch, H, Yoshida, A., Altland, K., Jensen, W., and Goedde, H. W., Structural difference at the active site of dibucaine resistant variant of human plasma cholinesterase. Am. J. Hum. Genet. 30, 302-307 (1978). 

The most common mutant is the so-called dibucaine-resistant enzyme variant. It is characterized principally by its reduced afiSnity for a series of substrates and inhibitors as compared with the normal pseudocholinesterase. Although at high concentrations succinyldicholine can also be converted by the dibucaine-resistant enzyme variant, the absence of enzymatic hydrolysis under pharmacologic conditions is adequately explained by the large difference in the Michaelis constants of succinyldicholine with the normal enzyme with the dibucaine-resistant variant Usually the variant is identified by the reduced inhibition of its reaction with the substrate benzoylcholine produced by the local anaesthetic dibucaine (cinchocaine). The percentage of inhibition by dibucaine under standard conditions, defined as the dibucaine number (DN). is about 20 for the dibucaine-resistant variant and app oximately 80 for the ordinary enzyme. Serum activity from heterozygotes having both enzymes is inhibited about 40-70%. 

The second so-called fluoride-resistant variant is similarly differentiated from the normal and dibucaine-resistant enzymes by its different sensitivity to the pseudocholinesterase inhibitor NaF. 

The frequency distribution of the allele for the dibucaine-resistant enzyme variant can be seen from Table 2. The expected frequency of homozygotes for the variant in European and North American populations is 1 2000-3000. The frequency of the fluoride-resistant variant has not been tested but it seems to be... 

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