152 THE BIOCHEMISTRY OF B VITAMINS 



Cytochrome c is a protein (M.W. about 13,000) containing as a pros- 

 thetic group the same iron-porphyrin unit, hematin, as occurs in hemo- 

 globin. 95 Unlike hemoglobin, though, it functions by changing its valency 

 state, alternately existing as a ferro and ferric complex. It is not auto- 

 oxidizable but can react with molecular oxygen only in the presence of a 

 specific enzyme, cytochrome c oxidase, which is itself a porphyrin deriva- 

 tive. 



The reduction of cytochrome c in vitro at a rate compatible with the 

 requirements of an actively metabolizing cell can be demonstrated either 

 with (1) certain dehydrogenases of organic metabolites for which no 

 other coenzyme requirement is known to exist, or with (2) the reduced 

 triphosphopyridine nucleotide, provided the neecssary flavin catalyst, 

 cytochrome c reductase, is present. S7 It seems logical to expect that a 

 third type system, involving the enzymes by which the majority of 

 dehydrogenations are initiated, the diphosphopyridine dehydrogenases, 

 would likewise be associated with the cytochrome c mechanism. In spite 

 of an intensive search, the enzyme (flavoprotein?) capable of linking the 

 two systems has yet to be well characterized, although crude preparations 

 which link the diphosphopyridine nucleotide-cytochrome c systems have 

 been reported. 96, 97 



The dehydrogenases having no recognized coenzymes which presumably 

 pass their hydrogen atoms directly to cytochrome c are: succinic acid 

 dehydrogenase, 91 lactic acid dehydrogenase, 98 ' " oc-glycerophosphate de- 

 hydrogenase II, 100 a formic acid dehydrogenase, 101 a fatty acid dehydro- 

 genase, 102 and sarcosine dehydrogenase. 103 Most of these enzymes are 

 intimately associated with the cell structure and cannot be brought into 

 solution. Since tissues from riboflavin deficient animals have a subnormal 

 amount of succinic acid dehydrogenase, 92 a question can be raised con- 

 cerning the possibility that not only this enzyme but also other insoluble 

 cytochrome-linked enzymes may be flavoproteins. 



In addition to these natural enzymatic systems, a number of phenols 

 and amines can directly (nonenzymatically) serve as artificial agents for 

 reducing cytochrome c. 95 



As is the case with the other dehydrogenase coenzymes, the reduction 

 of cytochrome c is brought about by a univalent change in which the 

 cytochrome c accepts the hydrogen atoms one at a time from the organic 

 substrates or reduced coenzymes. Each atom so transferred in effect 

 reduces a ferric-porphyrin group to the ferro complex with the accom- 

 panying creation of a hydrogen ion: 



[H]+Fe +++ complex "^-^ H++Fe++ complex 



The reduction causes a very distinctive alteration in the absorption 

 spectra of the porphyrin complex which can be followed spectrophoto- 



