490 X. BILE PIGMENT FORMATION, ETC. 



The irreversible alteration of the type of linkage may occur, how- 

 ever, only in an oxidation reaction facilitated by a less far-reaching 

 change of the hemoglobin structure, such as, for example, the removal 

 of the loosely bound histidine imidazole from the sphere of action 

 of the heme iron by a reversible change of structure in the protein. 

 The nature of the irreversible changes which follow and which 

 probably also involve the porphyrin ring is still obscure. 



The role of cyanide is certainly not due to its inhibiting action on 

 catalase, an explanation first given by Barkan, but later withdrawn. 

 Cyanide is needed in a concentration far in excess of that needed for 

 catalase inhibition, and is needed, also, in the absence of catalase. 

 The spectroscopic similarity of pseudohemoglobin to sulfhemoglobin, 

 and the fact that cyanide reacts with disulfide linkages producing 

 sulfhydryl and thiocyanate groups, led Lemberg and Callaghan to 

 an investigation of whether cysteine sulfhydryl groups of the globin 

 played a part in the reaction. The role of cyanide could possibly be 

 understood as reformation of sulfhydryl groups from disulfide groups 

 produced by hydrogen peroxide. It has indeed been found that 

 hematin, when exposed to the action of hydrogen peroxide in the 

 presence of cysteine and cyanide, yielded hematin compounds some- 

 what resembling cruoratin; by acid treatment of these, an alkali- 

 soluble porphyrin has been obtained which, according to the analysis, 

 contained one molecule of cysteine {169J/.). lodoacetic acid, however, 

 did not inhibit the production of either cruoralbin or choleglobin. 

 The problem is, therefore, still open. 



There is no evidence whatsoever that compounds of the type of 

 pseudohemoglobin or cruoralbin play a physiological role. Their 

 interest lies mainly in their similarity to choleglobin on the one hand 

 and to sulfhemoglobin on the other. 



7. SULFHEMOGLOBIN 



7.1. Historical 



In 1863 Hoppe-Seyler {1336) observed the formation of a greenish 

 hemoglobin derivative which he called "Schwefelmethamoglobin," 

 resulting from the action of hydrogen sulfide on oxyhemoglobin. The 

 substance was later renamed "sulfhemoglobin," and Keilin has shown 

 that the substance arising from hemiglobin and hydrogen sulfide is 

 different {cf. Chapter VI). Sulfhemoglobin was subsequently studied 



