Origin of Type-III Porphyrins in Nature

Abstract

A RECENT article by Marks¹ has reviewed the present state of knowledge concerning porphyrin biogenesis, A part of the pathway which has stimulated much speculation is the step involving the condensation of porphobilinogen (I) to uroporphyrinogen III, IV (iii). A good deal of information is available on the enzymes concerned. Briefly, it seems that two enzymes are involved, uroporphyrinogen-I-synthetase and uroporphyrinogen-III-co-synthetase. The first, when incubated with porphobilinogen (I), produces uroporphyrinogen I, IV (i), while in the presence of the second enzyme, the product is uroporphyrinogen III, IV (iii). Uroporphyrinogen I is not a substrate for the co-synthetase. (Ref. 1 gives a comprehensive bibliography.) Most attempts to explain this unusual cyclization have started from the assumption that the enzymes would utilize a pathway which could be illustrated by chemical condensations in vitro—and all have been criticized on the ground that they produce a mixture of porphyrin isomers of uncertain composition, whereas the enzymatic condensations are much more specific.