CYTOCHROMES 163 



It was long desirable to find a link between the di- and tri- 

 phosphopyridine nucleotides and the cytochrome system. For some 

 time it has been known that the old yellow enzyme, i.e., the 

 Warburg-Christian flavoprotein (62), was readily reduced by tri- 

 phosphopyridine nucleotide (63), but only very slowly oxidized by 

 cytochrome c (64). This link has recently been established by the 

 excellent isolation work of Haas, Horecker, and Hogness (65), who 

 isolated a flavo (mononucleotide) -protein which rapidly reduces 

 cytochrome c. It has been given the functional name "cytochrome 

 reductase." The coenzyme II dependent systems have thus been 

 satisfactorily linked to the iron-containing system. Cytochrome c 

 reductase does not hnk reduced coenzyme I with cytochrome c 

 (66). Haas, Horecker, and Hogness (65) believe that since the 

 reductase loses its power to reduce cytochrome c when subjected to 

 chemical treatments common to the preparation of the old Warburg- 

 Christian flavoprotein, it is very probable that the latter represents 

 a denatured product of cytochrome reductase. 



The story is less satisfactory than in the case of coenzyme I. In 

 1937 Adler, Euler, and Hellstrom (67) discovered an enzyme which 

 they called "diaphorase," and independently Green and Dewan 

 (68) investigated what was apparently the same enzyme, which they 

 called "coenzyme factor." This factor appeared to link coenzyme 

 I with the cytochrome system. Of significance for the present discus- 

 sion is the fact that Green and Dewan (68) stated that cytochromes 

 a and b but not c were involved in the reaction. The absence of 

 cytochrome c in their preparation has been challenged by Haw- 

 thorne and Harrison (69) and by Lockhart and Potter (66). The latter 

 authors have in fact demonstrated that cytochrome c is a link in the 

 aerobic oxidation of coenzyme I. They also have used two types of 

 "diaphorase" preparation, one of which catalyzed the coenzyme I 

 reduction of cytochrome c and the other did not. Both, however, 

 could catalyze the reduction of methylene blue. This recalls the 

 findings in connection with succinate reduction of cytochrome c; 

 in fact, Lockhart and Potter have noted that the preparation unable 

 to reduce cytochrome c contained no cytochrome b. Thus comes 

 the suggestion but not the proof that cytochrome b may be involved 

 as a link between coenzyme I dependent systems and cytochrome c. 



Straub (55) has isolated from heart muscle a flavoprotein which 

 is considered to be identical with the coenzyme factor or diaphorase. 

 Corran, Green, and Straub (70), in studying the catalytic proporties 

 of this flavoprotein, find that its reduced form is only slowly autoxi- 



