EXCRETION OF PORPHYRINS 587 



however, was of the weakest kind, being based on a difference of the 

 melting point depression obtained on mixing natural and synthetic 

 mesoporphyrin IX methyl esters with mesoporphyrin II ester. The 

 claim was later withdrawn in a somewhat obscure way (c/. 796,877; 

 also Rimington, 2268). 



A coproporphyrin derived from hemoglobin by decomposition can, 

 therefore, be only coproporphyrin III, while both coproporphyrin I 

 and coproporphyrin III may result as bj'-products of hemoglobin 

 synthesis (c/. Chapter XIII). The isomeride type of the porphyrins 

 found in the excreta is thus of physiologic interest, and has been 

 studied by a large number of workers; in fact perhaps a dispropor- 

 tionately large amount of energy has been spent in the attempt to 

 elucidate this problem. 



We have already discussed the experimental difficulties of the separation 

 of coproporphyrins I and III in Chapter III (Section 4.8.). The result 

 depends on melting point determinations of crystals obtained by fractional 

 crystallization. The uncertainties of the melting point determinations have 

 been discussed in Chapter III, Section 3.4.1. The success of the fractional 

 crystallization evidently depends a good deal on the amount of material 

 available, the skill of the operator, on the presence of impurities, and the 

 thoroughness with which mother liquors have been worked up. It is rather 

 significant that no exact estimations of the porphyrin remaining in the mother 

 liquor have been given, and that later investigators often found copropor- 

 phyrin III in addition to coproporphyrin I where earlier workers had only 

 reported the latter {cf. below). While, on the one hand, the final evidence 

 for the presence of coproporphyrin I is more certain than that for III, the 

 latter may have escaped detection in the mother liquors. 



With regard to uroporphyrin the difficulties are even greater. The investi- 

 gations of Watson and co-workers (1056,3002) and of Prunty [3193) make 

 it appear very doubtful whether the "uroporphyrin III" of Waldenstrom 

 can be considered a uniform substance [cf. Chapter III, Section 3. 4. '2.); it 

 probably contains a mixture of type I and type III porphyrins. The solu- 

 bility of type III uroporphyrin in ethyl acetate does not appear to be always 

 a reliable guide {cf. 2838), and there is no complete certainty about the 

 melting points of uroporphyrins, which may be lowered by impurities or 

 raised by complex salt formations with traces of metal. 



Moreover, if, as Waldenstrom found, and as we have also observed in one 

 case, the uroporphyrin is predominantly formed in vitro from dipyrrolic 

 porphobilinogen {cf. Chapter IV, Section 8.3.), it is very unlikely that a 

 single isomeride (particularly of the dissymmetrical type III) could arise. 

 The claim of Waldenstrom and Wendt {2912) that porphyrin is formed in 

 rabbit liver from injected porphobilinogen, has not been confirmed by 

 Prunty (2192). It is possible that the porphyrin mixture formed by the 

 action of acid on porphobilinogen in vitro differs from the uroporphyrin, 



