Synthetic and biosynthetic studies of porphyrins, part V: Evidence for an alternative pathway in the biosynthesis of haem

Patients suffering from porphyria cutanea tarda excrete relatively large amounts of porphyrins derived from intermediate porphyrinogens between the octacarboxylic uroporphyrinogen-III and the dicarboxylic protoporphyrinogen-IX. The four carboxyl fraction contains a group of four porphyrins related to dehydroisocoproporphyrin which arise by the action of coproporphyrinogen oxidase upon the pentacarboxylic precursor, before the final acetic acid residue is decarboxylated. Dehydroisocoproporphyrin, isocoproporphyrin, and desvinyldehydroisocoproporphyrin have now been synthesised and the corresponding porphyrinogens incubated with chicken red cell haemolysates. The products have been investigated by h.p.l.c. and mass spectrometry and provide clear evidence for an alternative pathway from the normal pentacarboxylic porphyrinogen precursor of coproporphyrinogen-III via harderoporphyrinogen to protoporphyrinogen-IX and haem. The significance of our findings in relation to haem biosynthesis in normal and abnormal metabolism is also discussed.