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

Concomitant i.v. use of cocaine and heroin (“speedballing”) is prevalent among drug-abusing populations. Heroin is rapidly metabolized by sequential deacetylation of two separate ester bonds to yield 6-monoacetylmorphine and morphine. Hydroly-sis of heroin to 6-monoacetylmorphine is catalyzed by pseudo-cholinesterase. The pathway for hydrolysis of 6-monoacetyl-morphine to morphine in vivo has yet to be established. Pseudocholinesterase and two human liver carboxylesterases [human liver carboxylesterase form 1 (hCE-1) and human liver carboxylesterase form 2 (hCE-2)] catalyze the rapid hydrolysis of ester linkages in cocaine. This investigation examined the relative catalytic efficiencies of hCE-1, hCE-2 and pseudocho-Iinesterase for heroin metabolism and compared them with cocaine hydrolysis. Enzymatic formation of 6-monoacetylmor