PATHWAYS OF CELLULAR OXIDATION 375 



which mediates between cytoclirome c and tripliospliopyridine nucleotide 

 (coenzyme II), the latter reacting with the glucose-G-phosphate dehy- 

 drogenase system. According to Ochoa {2062) cytochrome reductase also 

 reacts with isocitric acid dehydrogenase. Similarly diaphorase (also 

 called the coenzyme factor), an alloxazine adenine dinucleotide, mediates 

 between cytochrome c and diphosphopyridine nucleotide (coenzyme I), the 

 latter reacting with the lactic dehydrogenase of higher animals. The way 

 in which the cytochrome system is linked with succinic dehydrogenase and 

 also perhaps with diaphorase is not yet clear (rf. Slater, 2')71a). The role of 

 cytochrome b. which is probably required for this reaction, has been dis- 

 cussed in Section 3.4. 



A turnover number of 3850 valency changes of cytochrome c per 



minute has been found by Keilin and Hartree {1J^9I^) in the yeast 



cell, a somewhat smaller figure — 1400 — in the isolated cytochrome 



oxidase-cytochrome c system. In those cells in which the complete 



cytochrome system has been observed spectroscopically, we thus 



probably have the system : 



oxidase-cytochrome a-oytochrome c-cytochrome b 



\ / 



hydrogen donor 



It is still doubtful whether similar systems are at work in organisms or 

 tissues in which different cytochromes can be observed spectroscopically. 

 Cytochrome a.i can probably fully or partially replace the cytochrome oxidase 

 in the microorganisms in which it occurs, for instance in Azotobacter {2025), 

 but our knowledge of these systems is still so incomplete that there exists 

 little more than speculation with regard to the pathways of hematin-catalyzed 

 oxidation in such organisms. 



The cytochrome system can probably react also with other metabolites 

 in addition to those mentioned above. Caution is required, however, in 

 attributing any reaction which can be shown to be accelerated by cytochrome 

 c to the action of cytochrome oxidase. Green and Richter (lO^Jf) found a 

 strong oxygen uptake by systems consisting of animal lactic and malic acid 

 dehydrogenases, cyanide (whicli combines with the oxidation products, pyru- 

 vic or oxalacetic acid), adrenaline, and cytochrome c. Cytochrome c was 

 found necessary for the production of adrenochrome from adrenaline. In 

 this system it may be oxidized to ferricytochrome c by the hydrogen peroxide 

 resulting from the autoxidation of leucoadrenochrome. Similarly Hermann 

 and co-workers {12^o) observed that cytochrome c increased the rate of 

 oxidation of ascorbic acid in the presence of oxidized adrenaline. 



In recent experiments carried out at this Institute by Mr. J. E. Falk, it 

 was found that cytochrome c catalyzes the oxidation of ascorbic acid in the 

 presence of adrenaline (or of some drugs of the acridine and quinoline series), 

 by acting unspecifically as hematin peroxidase on adrenaline or the drugs. 

 The quinoid systems thus produced then catalyze the oxidation of ascorbic 

 acid by oxygen. The small amounts of hydrogen peroxide which initiate 



