| Abstract
| - Coproporphyrinogen oxidase (copro'gen oxidase) catalyses the oxidative decarboxylation of twopropionate side chains on coproporphyrinogen-III to produce protoporphyrinogen-IX. This processis very poorly understood at a molecular level, and copro'gen oxidase remains one of the least well-characterized enzymes in the heme biosynthetic pathway. To provide a rigorous test for a proposedmodel for substrate recognition and binding by this enzyme, two tripropionate analogues ofcopro'gen-III were prepared where an ethyl group replaced one of the usual propionate residues onpositions 13 or 17. Although the required substrate probes are porphyrinogens (hexahydroporphyrins), the corresponding porphyrin methyl esters were initially synthesized via tripyrrene and a,c-biladiene intermediates. These were hydrolyzed and reduced with 3% sodium-amalgam to give theunstable porphyrinogens needed for the biochemical investigations. The modified structure with a13-ethyl moiety was metabolized by avian preparations of copro'gen oxidase to give a monovinylicproduct, but the isomeric 17-ethylporphyrinogen afforded a divinylic product, albeit with pooreroverall conversion. These results strongly support the proposed model for substrate binding at theactive site of copro'gen oxidase.
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