TY - JOUR
T1 - Hydrolysis of diacetylmorphine (heroin) by human serum cholinesterase
AU - Lockridge, O.
AU - Mottershaw-Jackson, N.
AU - Eckerson, H. W.
AU - La Du, B. N.
PY - 1980
Y1 - 1980
N2 - 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 μmol of heroin hydrolyzed per min per μmol active site. The product was identified spectrophotometrically and by thin-layer chromotography to be 6-acetylmorphine. There appeared to be marked product inhibition of heroin hydrolysis, as 6-acetylmorphine (K(i) = 0.015 mM) bound 7 times more tightly than heroin (K(i) = 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 also tested. Serum from a person identified as having silent cholinesterase did not hyrolyze heroin. Purified atypical cholinesterase hydrolyze heroin, but the binding was less tight K(m) = 0.45 mM) than with usual cholinesterase K(m) = 0.11 mM). The possibility that heroin potency may be influenced by serum cholinesterase genotype or activity level remains to be investigated.
AB - 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 μmol of heroin hydrolyzed per min per μmol active site. The product was identified spectrophotometrically and by thin-layer chromotography to be 6-acetylmorphine. There appeared to be marked product inhibition of heroin hydrolysis, as 6-acetylmorphine (K(i) = 0.015 mM) bound 7 times more tightly than heroin (K(i) = 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 also tested. Serum from a person identified as having silent cholinesterase did not hyrolyze heroin. Purified atypical cholinesterase hydrolyze heroin, but the binding was less tight K(m) = 0.45 mM) than with usual cholinesterase K(m) = 0.11 mM). The possibility that heroin potency may be influenced by serum cholinesterase genotype or activity level remains to be investigated.
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M3 - Article
C2 - 7452476
AN - SCOPUS:0019289017
VL - 215
SP - 1
EP - 8
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -