Heroin metabolism processes

During heroin metabolism, the acetyl groups must be cleaved to yield morphine this might simply be hydrolysis or it may be an enzyme-mediated process. Codeine is also demethylated this is known to be an enzyme-mediated process (there are no simple chemical processes that would achieve this under physiological conditions), and some 10 %-15 % of the population are deficient in the enzyme, so codeine is not converted to morphine, and codeine has little analgesic effect for this group. Another 10 % of the population has overactivity of the enzyme, so that the codeine is demethylated very rapidly and effectively, and they must be careful not to consume an overdose, which would be less for them than for someone with more standard enzyme activity. Finally, in order to be excreted effectively in urine, the morphine is converted to a sugar derivative, to ensure water solubility. 

Heroin is rapidly hydrolyzed in vivo to 6-monoacetylmorphine (257) and thence to morphine (1) (see also p. 26). N-Demethylation and O-demethyla-tion are significant metabolic routes in animals, with the former oxidative process leading to normorphine (258) from 1, and norcodeine (259) from 2, which may in turn be eliminated as their 3- and 6-glucuronides, respectively. 

Bencharit, S., Morton, G. L., Xue, Y, Potter, P. M., Redinbo, M. (2003). Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nature Structural... 

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