Normal and abnormal heme biosynthesis. 2. Synthesis and metabolism of type-III pentacarboxylic porphyrinogens: Further experimental evidence for the enzymic clockwise decarboxylation of uroporphyrinogen-III

Uroporphyrinogen decarboxylase catalyses the sequential decarboxylation of uroporphyrinogen-III (1) to-give coproporphyrinogen-III (2), a precursor to the hemes and chlorophylls. This involves the decarboxylation of four none quivalent acetate side chains to produce methyl units and in principle coul d take place by 24 different pathways involving up to 14 intermediary porph yrinogens. In the past, seemingly contradictory data have been presented th at either support an ordered "clockwise" decarboxylation pathway or a rando m decarboxylation process. Four pentacarboxylate porphyrinogens might be in volved immediately before the formation of 2, and these compounds have been synthesized as the corresponding porphyrin pentamethyl esters via tripyrre ne and a,c-biladiene intermediates. Hydrolysis of the methyl esters and red uction with 3% sodium amalgam gave the required porphyrinogens, and these w ere incubated with crude enzyme preparations derived from chicken red cell hemolysates. One of these pentacarboxylate porphyrinogens (5dab) consistent ly proved to be a much better substrate than the other three, providing new support for the "clockwise" pathway for coproporphyrinogen-III formation.