The IX-α Structure of the Common Bile Pigments

Abstract

IT is generally accepted that all the naturally occurring ‘tetrapyrrolic’ bile pigments must be of a IX-α structure, that is, that they are derived from the biliverdin which is produced biologically by rupture of the α-methene bridge carbon atom of protoporphyrin IX. Therefore, all bile pigments prepared from biological material should possess a 1,3,6,7-tetramethyl-4,5-dicarboxyethyl-2,8-divinyl (or diethyl), open-chain, ‘tetrapyrrolic’ structure (using the system of numbering shown in formula (I). Although some of the bile pigments have been synthesized by methods which exclude the formation of isomers other than IX-α, there is, at present, no analytical evidence of the absence of such isomers in the pigments obtained from biological sources. The presence of such isomers would be expected if biological fission of the protoporphyrin molecule did not occur exclusively at the α-methene linkage. Since stercobilin (and therefore also the less-hydrogenated bile pigments) is known to be produced by at least two distinct physiological mechanisms¹, such a possibility is not entirely speculative. The method of identification of pyrrole carboxylic acids described by one of us and used in investigations of the porphyrins² has now been applied to a study of the order of the β-side-chains of the bile pigments. In the bile pigments one α-position of each end ring bears an oxygen atom (usually formulated in a hydroxyl group³) instead of a carbon atom. It is therefore impossible for these rings, on degradation, to provide the αα′-pyrroledicarboxylic acids given under similar conditions by the corresponding porphyrins; any such acids can only originate from the middle rings of the pigment molecule.