Biosynthesis of porphyries and related macrocycles. Part 17. Chemical and enzymic transformation of isomeric aminomethylbilanes into uroporphyrinogens: proof that unrearranged bilane is the preferred enzymic substrate and detection of a transient intermediate

Abstract

Six isomeric aminomethylbilanes have been built by unambiguous synthesis. One bilane has the unrearranged structure corresponding to straightforward head-to-tail assembly of four units of porphobilinogen; the other five bilanes have one or more of the pyrrole rings reversed relative to the unrearranged bilane. The action of deaminasecosynthetase on these bilanes has been studied and the results showed that (a) the enzyme system ring closes the unrearranged bilane far more efficiently than it closes any of the five isomeric bilanes, (b) under the best conditions the product formed enzymically from the unrearranged bilane is almost pure uroporphyrinogen-III, and (c) a transient intermediate is formed enzymically from the unrearranged bilane which can be detected kinetically. Further support is thereby given to the earlier conclusion that the intramolecular rearrangement which produces the natural type-III porphyries occurs at the unrearranged tetrapyrrole level.

The enzymic results for the other bilanes are also described together with an improved method for analytical separation of the four isomeric esters of coproporphyrin.