HEMOPROTEIN-MEDIATED METABOLISM OF ENAMINES AND THE POSSIBLE INVOLVEMENT OF ONE-ELECTRON OXIDATIONS

1. Microsomal metabolism of 1-benzylpiperidine (1-BP), its cis-2,6-dim ethyl (cis-2,6-DMBP), 4,4-dimethyl (4,4-DMBP), and alpha,alpha-dimethy l (alpha,alpha-DMBP) analogues, and phencyclidine (PCP) has been studi ed to assess the involvement of P450 oxidation of the enamine tautomer s of the initial endocyclic iminium metabolites. 2. The selective prev ention by cyanide of the metabolite production of 1-benzyl-3-piperidon e but not 1-benzyl-3-piperidinol from 1-BP is consistent with the enam ine as the source of the 3-one metabolite. 3. The parent amines and pa rticularly the independently prepared iminium species induced a patter n of metabolism-dependent irreversible inactivation of P450 benzphetam ine demethylase activity, consistent with involvement of enamine C-3 o xidation in the inactivation process. 4. Substrate activity of the end ocyclic enamines and alpha-aminoketones (presumably the enol-enamine t automers) for horseradish peroxidase under conditions where simple ali phatic amines display no activity is consistent with metabolic one-ele ctron oxidations of the enamines.