Metabolism of Analogues of Coproporphyrinogen-III with Modified Side Chains: Implications for Binding at the Active Site of Coproporphyrinogen Oxidase

Porphyrinogens with modified propionate side chains bearing methyl substituents were found to be modest substrates for coproporphyrinogen oxidase; the results indicate that alteration of the substituents involved in secondary binding interactions has a comparable affect to modifying the side chain that undergoes degradation at the catalytic site. Coproporphyrinogen-III analogues with methyl units appended to the A or B ring propionate groups are shown to be moderate to poor substrates for coproporphyrinogen oxidase, a critical enzyme in the heme biosynthetic pathway; these results provide new insights into the binding specificity of this poorly understood enzyme.