Sydney G. Smith

The metabolism of coproporphyrinogen-III into protoporphyrin-IX

Abstract This review considers the stages and enzymes between coproporphyrinogen-III and protoporphyrin-IX.

The separation of free dicarboxylic acid porphyrins using thin-layer and paper chromatography

Abstract Mixtures of protoporphyrin, deuteroporphyrin, haematoporphyrin, pemptoporphyrin and mesoporphyrin can be separated as free acids on talc thin-layer chromatography plates by developing them with a mixture of ethanol-2,6-lutidine-water (30:3:67) in tanks containing an atmosphere saturated with ammonia vapour. Monoacrylic monopropionic deuteroporphyrin (“S/411” porphyrin) can be separated from coproporphyrin using this system. The same mixture of two carboxyl porphyrins can also be separated on Whatman No. 1 chromatography paper by developing with pyridine-0.2 M sodium borate buffer pH 8.6 (1:9) by either ascending or descending techniques.

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

Abstract 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.

Biliary protein-bound porphyrins in porphyria variegata

Abstract Duodenal aspirate from two unrelated male subjects carrying the Mendelian dominant variegate porphyria gene was examined for hydrophilic “X” porphyrins and found to give a similar pattern to that observed previously in faeces. However, an insoluble, presumably high molecular weight porphyrin-peptide is described which has not as yet been reported in faeces. The hydrophilic “X”-porphyrins show remarkable resistance to the proteolytic enzymes of the intestine.

Specificity of coproporphyrinogen oxidase: conversion of coproporphyrinogen-IV into protoporphyrin-XIII

Coproporphyrinogen-IV (1b) is converted into protoporphyrin-XIII by avian haemolysates, and the structure of the product confirmed by total synthesis.

Mesoporphyrinogen-VI: a substrate for coproporphyrinogen oxidase

Mesoporphyrinogen-IV is metabolised by coproporphyrinogen oxidase to ‘protoaetioporphyrin,’ thus showing that the two vicinal propionic acid groups which are present in all other known substrates are not essential for substrates of this enzyme.