636 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



Later theories are concerned only with the explanation of the 

 synthesis of the various porphyrins from postulated pyrromethene 

 precursors. A sound theory of porphyrinogenesis should explain the 

 formation of the variety of porphyrins which have been summarized 

 in Figure 1, and the nonoccurrence of other isomerides. In this the 

 present theories of porphyrin formation still fail to a large extent. 

 In 1936 Rimington {2257-2259) and Dobriner and co-workers {601, 

 602,604) independently suggested the following theory, assuming two 

 pyrromethenes A and B as precursors (Fig. 2). By condensation with 

 one another they yield protoporphyrin IX which is largely converted 

 into hemoglobin. This is the main reaction, probably under enzymic 

 control. A small amount of A (about 1 part in 10,000) condenses with 

 itself to yield a (hypothetical) type I porphyrin with four vinyl side 

 chains. This is assumed to be converted to coproporphyrin I by 

 addition of formic acid to its vinyl side chains, and under pathologic 

 conditions, by further carboxylations (methyl — > acetic acid side 

 chains) to uroporphyrin I. Coproporphyrin III may be assumed to 

 be derived by the reaction of protoporphyrin IX with formic acid. 

 Autocondensation of pyrromethene B should yield coproporphyrin II, 

 but this has not been found. The theory necessitates the assumption 

 that vinyl side chains can be transformed to propionic acid side 

 chains; we have seen in Chapter XII, Section 3.2.4., that there is no 

 reliable evidence for this reaction. The carboxylation of a methyl to 

 an acetic acid side chain, which is necessary for the explanation of the 

 formation of uroporphyrin under pathologic conditions and in the 

 embryo, is still less likely. The greatest weakness of the theory is, 

 however, that the assumption of the two precursor pyrromethenes 

 A and B is an ad hoc hypothesis which begs the" question. 



The same criticism can be raised against the theory of Turner 

 {283.9). Turner, however, was the first to suggest that the primary 

 precursor contains acetic acid and propionic side chains, like uro- 

 porphyrins, and that the precursors of coproporphyrin and protopor- 

 phyrin are derived from it by decarboxylation (Fig. 3). 



The primary' precursor was assumed to condense to tripj^ryl- 

 methanes which by splitting at different linkages yielded the pyrro- 

 methenes required for the porphyrin synthesis (c/. Fig. 3). 



Not only are the particular tripyrrylmethanes arbitrarily chosen, 

 but so also are the linkages which are ruptured to form pyrromethenes. 

 The formation of such tripyrrylmethanes could only increase the 

 number of possible porphyrins in excess of the number actually 



