Lockridge O, Mottershaw-Jackson N, Eckerson H W, La Du B N
J Pharmacol Exp Ther. 1980 Oct;215(1):1-8.
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 mumol of heroin hydrolyzed per min per mumol active site. The product was identified spectrophotometrically and by thin-layer chromatography to be 6-acetylmorphine. There appeared to be marked product inhibition of heroin hydrolysis, as 6-acetylmorphine (Ki = 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 also tested. Serum from a person identified as having silent cholinesterase did not hydrolyze heroin. Purified atypical cholinestearase 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.
本报告中确定，人血清中能迅速将二乙酰吗啡（海洛因）水解为6-乙酰吗啡的酶是血清胆碱酯酶（EC 3.1.1.8，酰基胆碱酰基水解酶；也称为假性胆碱酯酶或丁酰胆碱酯酶）。使用高度纯化的血清胆碱酯酶，通过分光光度法在245nm处测定海洛因的水解速率。转换数为每分钟每微摩尔活性位点水解500微摩尔海洛因。通过分光光度法和薄层色谱法鉴定产物为6-乙酰吗啡。似乎存在明显的产物抑制海洛因水解的现象，因为6-乙酰吗啡（Ki = 0.015 mM）的结合比海洛因（Ki = 0.11 mM）紧密7倍。纯化的人血清芳基酯酶不水解海洛因。纯化的血清胆碱酯酶解释了全血清中观察到的所有海洛因水解现象。还对人血清胆碱酯酶的基因变体，即沉默型和非典型胆碱酯酶进行了测试。来自一名被鉴定为具有沉默型胆碱酯酶的人的血清不水解海洛因。纯化的非典型胆碱酯酶水解海洛因，但结合不如正常胆碱酯酶紧密（Km = 0.45 mM）（Km = 0.11 mM）。海洛因效力是否可能受血清胆碱酯酶基因型或活性水平影响的可能性仍有待研究。
