Human erythrocyte but not brain acetylcholinesterase hydrolyses heroin to morphine

1. In human blood, heroin is rapidly hydrolysed by sequential deacylation o f two ester bonds to yield first 6-monoacetylmorphine (6-MAM), then morphin e. 2. Serum butyrylcholinesterase (BuChE) hydrolyses heroin to 6-MAM with a ca talytic efficiency of 4.5/min per mu mol/L, but does not proceed to produce morphine. 3. In vitro, human erythrocyte acetylcholinesterase (AChE) hydrolyses heroi n to 6-MAM, with a catalytic efficiency of 0.5/min per mu mol/L under first -order kinetics. Moreover, erythrocyte AChE, but not BuChE is capable of fu rther hydrolysing 6-MAM to morphine, albeit at a considerably slower rate. 4. Both hydrolysis steps by erythrocyte AChE were totally blocked by the se lective AChE inhibitor BW284c51 but were not blocked by the BuChE-specific inhibitor, iso-OMPA (tetraisopropylpyrophosphoramide). 5. The brain synaptic form of AChE, which differs from the erythrocyte enzy me in its C-terminus, was incapable of hydrolysing heroin. 6. Heroin suppressed substrate hydrolysis by antibody-immobilized erythrocy te but not by brain AChE. 7. These findings reveal a new metabolic role for erythrocyte AChE, the bio logical function of which is as yet unexplained, and demonstrate distinct b iochemical properties for the two AChE variants, which were previously cons idered catalytically indistinguishable.