Porphyrin Biosynthesis in Erythrocytes

The porphyrinogens are colorless, reduced porphyrins containing 6 extra atoms of hydrogen. They have been reported to occur in biological materials by Fischer, who isolated COPRO’gen’ from the feces of his porphyria patient Petry (l), and by Watson, Schwartz, and coworkers, who showed that COPRO’gen was present in the urine of some of their patients with various porphyrias (2). Suspicions that these porphyrinogens are the actual intermediates in the biosynthesis of porphyrins arose when it was observed that the porphyrins themselves, i.e. URO and COPRO, could not be used for heme or chlorophyll synthesis by either intact or disrupted cells (3-5). The structure of porphobilinogen gave further indirect evidence for this view since a condensation of 4 molecules of this pyrrole would produce URO’gen (6). Also, Bogorad obtained small amounts of COPRO on incubating reduced URO with a preparation from Chlorella (5), and Neve, Labbe, and Aldrich have found that adding reduced URO to hemolyzed red cells increased the incorporation of Fe6s into heme (7). We have isolated by zone electrophoresis on starch an enzyme preparation from red cells which decarboxylates uroporphyrinogen but not uroporphyrin, yielding coproporphyrinogen as the final product. Some observations have been made on the photocatalytic autoxidation of URO’gen, and the structure of compounds at levels of reduction intermediate between TJRO and URO’gen is discussed.