Metabolism of cocaine and heroin is catalyzed by the same human liver carboxylesterases.

摘要: Concomitant i.v. use of cocaine and heroin ("speedballing") is prevalent among drug-abusing populations. Heroin rapidly metabolized by sequential deacetylation two separate ester bonds to yield 6-monoacetylmorphine morphine. Hydrolysis catalyzed pseudocholinesterase. The pathway for hydrolysis morphine in vivo has yet be established. Pseudocholinesterase human liver carboxylesterases [human carboxylesterase form 1 (hCE-1) 2 (hCE-2)] catalyze the rapid linkages cocaine. This investigation examined relative catalytic efficiencies hCE-1, hCE-2 pseudocholinesterase metabolism compared them with hydrolysis. Enzymatic formation was determined reverse-phase high-performance liquid chromatography. All three enzymes (hCE-1 kcat = 439 min-1, 2186 min-1 13 min-1). efficiency, under first-order conditions, hCE-2-catalyzed (314 mM-1) much greater than that either hCE-1 or (69 4 mM-1, respectively). Similarly, efficiency (22 substantially (0.024 mM-1). Cocaine competitively inhibited hCE-1-, hCE-2- pseudocholinesterase-catalyzed (Ki 530, 460 130 microM, respectively) 710, 220 830 These data demonstrate humans mediated common metabolic pathways. role hepatic particularly important