Normal and Abnormal Heme Biosynthesis. 2.1 Synthesis and Metabolism of Type-III Pentacarboxylic Porphyrinogens: Further Experimental Evidence for the Enzymic Clockwise Decarboxylation of Uroporphyrinogen-III

Abstract

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 nonequivalent acetate side chains to produce methyl units and in principle could take place by 24 different pathways involving up to 14 intermediary porphyrinogens. In the past, seemingly contradictory data have been presented that either support an ordered “clockwise” decarboxylation pathway or a random decarboxylation process. Four pentacarboxylate porphyrinogens might be involved immediately before the formation of 2, and these compounds have been synthesized as the corresponding porphyrin pentamethyl esters via tripyrrene and a,c-biladiene intermediates. Hydrolysis of the methyl esters and reduction with 3% sodium amalgam gave the required porphyrinogens, and these were incubated with crude enzyme preparations derived from chicken red cell hemolysates. One of these pentacarboxylate porphyrinogens (5dab) consistently proved to be a much better substrate than the other three, providing new support for the “clockwise” pathway for coproporphyrinogen-III formation.