Biosynthesis of porphyrins and related macrocycles. Part 14. Studies with [14C]isoporphobilinogen and four isomeric labelled pyrromethanes: specific conversion of the unrearranged pyrromethane NH3.AP.AP into haem and protoporphyrin-IX

Abstract

[11-¹⁴C]Isoporphobilinogen and ¹⁴C-, and ¹³C-labelled forms of four isomeric pyrromethanes have been synthesised in order to study at what stage in the building process rearrangement occurs to produce the natural porphyrins. The finding that isoporphobilinogen is not a biosynthetic precursor of protoporphyrin-IX points against the rearrangement being at the monopyrrole level. Of the four pyrromethanes, only the unrearranged system NH₃.AP.AP (5) is significantly converted, in the presence of the necessary enzymes from Euglena gracilis or duck's blood, into protoporphyrin-IX or haem. Degradation of these products from ¹⁴C-labelled (5) proved that the conversion of NH₃.AP.AP into the type-III macrocycle occurs without randomisation of the labels; this conclusion was rigorously confirmed by ¹³C-n.m.r. spectra from samples of ¹³C-protoporphyrin-IX produced enzymically from ¹³C-labelled (5).