A Pseudocholinesterase Variant in Human Tissues

Journal/Book: Reprinted from Nature Vol. 198 No. 4885 pp. 1090-1091 June 15 1963. 1963;

Abstract: Nuffield Department of Clinical Biochemistry Radcliffe Infirmary Oxford. PSEUDOCHOLINESTERASE activity has been found in human serum and in many other tissues1 and while it is accepted that the serum enzyme is manufactured in the liver the question arises whether the pseudocholinesterases found in other organs are identical with that of the liver and serum. Differences in the bio-chemical behaviour between the pseudocholinesterases of different species have been demonstrated but there is no conclusive evidence to show whether the pseudocholinesterases found in various tissues of the same species are different protein molecules2. Such differences have been found with some other enzymes for example the lactic dehydrogenases and the acid and alkaline phosphatases. Several genetically determined variants of serum pseudocholinesterase have been described3-5. That most commonly seen is an ´atypical' enzyme which differs from the normal in having a lower hydrolytic activity with a wide range of substrates and a greater resistance to the majority of cholinesterase inhibitors6 7. The demonstration of this variant in the tissues as well as in the sera of affected individuals would indicate that the same gene determined the production of both enzyme molecules. We have been able to obtain post-mortem tissue specimens both from a homozygote with the atypical serum enzyme and from a heterozygote with both the normal and the atypical variants. The genotypes of those individuals were confirmed by family investigations. The local anæsthetic ´Dibucaine' (´Cinchocaine' ´Nupercaine') is a differential inhibitor frequently used to identify sera from the three genotypos8. In this technique the hydrolysis of a 5 x 10-5 M concentration of benzoylcholine is measured spectrophotomotrically both with and without the addition of a 10-6 M final concentration of ´Dibucaine'. The pseudocholinesterase of normal serum is inhibited by about 80 per cent and that from an atypical homozygote by only about 20 per cent while the activities of sera from heterozygotes are inhibited by between 50 and 70 per cent. ... ___MH

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