240 VI. HEMOGLOBIN 



rhodohemin, diacetyldeuterohemin, and pheohemin-6, which combined revers- 

 ibly with oxygen. The oxyhemoglobins of the first two showed a typical 

 two-banded spectrum. These results show that the vinyl side chains in 

 protohemin can be converted to ethyl groups in mesohemin, hydroxyethyl 

 groups in hematohemin, and transformed to acetyl groups in diacetyldeutero- 

 hemin, without affecting the specific heme-globin linkage in the process. 



Bile pigment hematins (Chapter X, 2.3.) and monazahematins (Chapter 

 V, 8.2.), as well as pheophorbide-6 hematin {295Jf.), have been shown to com- 

 bine with globin to form compounds which are unable to combine with 

 oxygen. Further investigations are needed to decide whether this is due to 

 their inability to form the same type of linkage with the globin as in proto- 

 hemoglobin, or whether it is due to the alteration in the structure of their 

 resonance system. 



All the above hemins, however, still possess carboxyl groups. No work 

 has been reported on any of the hemins which do not carry carboxylic acid 

 side chains, perhaps because of their insolubility. Haurowitz {1177) has 

 reported that the dimethyl ester of mesohemin is able to form a hemoglobin; 

 it is possible, however, that saponification of the ester occurred in the alkaline 

 globin solution. Since Holden {1317) has recently revived the idea that the 

 carboxyl groups are involved in the linkage, experiments with heme lacking 

 these groups are urgently needed. 



3.3.3. Compounds of Globin with Porphyrin and Nonferrous Metallo- 

 porphyrins. The possible role which the carboxylic acid side chains of the 

 hematin might play in linkage to globin can be seen in the porphyrin globin 

 compound. Hill and Holden (1282) observed that when protoporphyrin, 

 mesoporphyrin, or hematoporphyrin are combined with globin, the color 

 changes from brownish-red to pink and the absorption bands in the visible 

 region become sharp. The Soret band also becomes stronger, indicating a 

 change in the degree of aggregation of the porphyrin {1501).) and the porphyrin 

 is no longer adsorbed on calcium carbonate. While serum albumin {cf. 

 Section 3.3.5.) causes slight spectral changes when added to an alkaline 

 porphyrin solution {1177,1310), denatured globin {1282) and casein {1310) do 

 not do so. 



Native globin is able to combine with between fpur and eight porphyrin 

 molecules {1282,1310) ; Hill and Holden {1282) were able to displace hemato- 

 porphyrin from combination with globin by the addition of hematin; hemo- 

 globin was formed while the spectrum of alkaline porphyrin reappeared. 

 The porphyrin is thus displaced from a position on the globin which is 

 adjacent to, if not identical with, tliat occupied by hematin. This important 

 experiment should be repeated, using spectrophotometric methods. 



Globin combines with a number of nonferrous metalloporphyrins. The 

 manganese, cobalt, nickel, copper, zinc, or tin mesoporphyrin compounds 

 show sharpening and shifting of absorption bands when slightly alkaline 

 solutions of these substances are allowed to stand with native globin {1282). 

 Similar compounds of protoporphyrin with copper, nickel, cobalt, and zinc 

 have been shown to combine with globin {1312). Taylor {27jlf9) has shown 

 that the cobalt and manganese mesoporphyrins are capable of combining 



