HYDROLYSIS OF DIACETYLMORPHINE (HEROIN) BY HUMAN-SERUM CHOLINESTERASE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 215  (1) , 1-8
Abstract
The enzyme in human serum that rapidly hydrolyzes diacetylmorphine (heroin) to 6-acetylmorphine is identified in this report as serum cholinesterase (EC 3.1.1.8, acylcholine acylhydrolase; also called pseudocholinesterase or butyrylcholine esterase). The rate of heroin hydrolysis was measured spectrophotometrically at 245 nm using highly purified serum cholinesterase. The turnover number was 500 .mu.mol heroin hydrolyzed/min per .mu.mol active site. The product was identified spectrophotometrically and by TLC as 6-acetylmorphine. There appeared to be marked product inhibition of heroin hydrolysis, as 6-acetylmorphine (Ki [inhibition constant] = 0.015 mM) bound 7 times more tightly than heroin (Ki = 0.11 mM). Purified human serum arylesterase did not hydrolyze heroin. Purified serum cholinesterase accounted for all the observed heroin hydrolysis by whole serum. The genetic variants of human serum cholinesterase, silent and atypical cholinesterase, were tested. Serum from a person identified as having silent cholinesterase did not hydrolyze heroin. Purified atypical cholinesterase hydrolyzed heroin, but the binding was less tight (Km = 0.45 mM) than with usual cholinesterase (Km = 0.11 mM). The possibility that heroin potency may be influenced by serum cholinesterase genotype or activity level remains to be investigated.