178 T. E. CONOVER 



oxidation of pyridine nucleotide-linked substrates by the addition of 

 vitamin Kg. However, DT diaphorase seems to play no role in the normal 

 respiration of mitochondria. Some coupling of mitochondrial DT dia- 

 phorase to the respiratory chain by naturally occurring quinones may 

 occur and may indeed account for the observed TPNH oxidase and cyto- 

 chrome r-reductase activity in mitochondria; however, the necessity for 

 such a pathway is difficult to comprehend. 



In conclusion, it must be said that though a role for DT diaphorase in 

 cellular respiration has been diligently searched for, the evidence of its 

 participation in this role is rather meagre. Figure 7 is recorded with some 

 hesitation as it probably implies more than may actually be the case. It is 

 possible that when TPNH levels are high that DT diaphorase may func- 

 tion as is diagrammatically shown and as has been shown to occur with 



Cytoplasm 



Mitochondria 



/3-OH-But. dehyd, Transhydrogenose 

 Lactic dehyd. malic dehyd. glut, dehyd 



etc etc etc 



TPNH ^;=:^ DPNH ^;^==^ DPNH ^^=!= TPNH 



Fig. 7. Some possible pathways of reduced pyridine nucleotide oxidation 

 and its regulation. 



added vitamin Kg. This pathway would require the presence of some 

 natural mediator, presumably of a quinone type, to function between DT 

 diaphorase and the respiratory chain. It may be emphasized that in liver 

 at least it is the absence or unavailability of sufficient amounts of such a 

 low molecular weight mediator that is essential for the maintenance of the 

 high levels of TPNH, rather than the absence of an enzyme which can 

 oxidize TPNH. Similar conclusions have been reached by Wenner [18] in 

 regard to the operation of the glucose-6-phosphate shunt in ascites tumour 

 cells. 



If speculation on the basis of the quinone-specificity of this pathway 

 would suggest a quinone of the vitamin K type in this role, it raises the 

 interesting possibility of regulation of TPNH levels by a factor of nutritional 



