Ketene, reaction with proteins

The oxidation of terminal acetylenes, like that of monosubstituted olefins, often results in inactivation of the P450 enzyme involved in the oxidation. In some instances, this inactivation involves reaction of the ketene metabolite with nucleophilic residues on the protein [196, 197], but in other instances it involves alkylation of the prosthetic heme group (Fig. 4.31). Again, as found for heme alkylation in the oxidation of olefins, the terminal carbon of the acetylene binds to a pyrrole nitrogen of the heme and a hydroxyl is attached to the internal carbon of the triple bond. Of course, as one of the two m-bonds of the acetylene remains in the adduct, keto-enol equilibration yields a final adduct structure with a carbonyl on the original internal carbon of the triple bond [182, 198]. It is to be noted that the oxidation of terminal triple bonds that produces ketene metabohtes requires addition of the ferryl oxygen to the imsubstituted, terminal carbon, whereas the oxidation that results in heme alkylation requires its addition to the internal carbon. As a rale, the ratios of metabolite formation to heme alkylation are much smaller for terminal acetylenes than for olefins. 

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