490 5. QUINONES 



reductive energy for the restoration of hemoglobin. Supniewski et al. 

 (1936) reported an odd biphasic action, difficult to explain, in that low con- 

 centrations (around 0.05 mM) of phthiocol depress the respiration of 

 mouse erythrocytes while higher concentrations (0.5-2.6 mM) progressively 

 stimulate. Actually these mechanisms involving hemoglobin may well 

 occur in other cells with various substances taking the place of hemoglobin. 

 Stimulation of respiration probably depends to a great extent on the state 

 of the cells and particularly on how active the respiration is. For example, 

 several investigators have found yeast respiration to be inhibited readily 

 by 29-benzoquinone, but Lejhanec et al. (1931) observed quite marked stim- 

 ulation at 0.018 mM, the oxygen uptake sometimes increasing as much as 

 2- to 10-fold, and the explanation for this discrepancy may well be that 

 the respiratory rate was for some reason rather low in the experiments of 

 Lejhanec. Chlorella respiration in the presence of glucose is inhibited by 

 phthiocol at 0.1 mM, but when the cells are starved and the rate initially 

 low the respiration may be stimulated as much as 15-fold by phthiocol 

 (Gaffron, 1945), and the respiration of substrate-depleted yeast is more apt 

 to be stimulated by low concentrations of various quinones than is the 

 respiration of fresh yeast (Flaig and de Jong, 1960 a). 



Comparison of the effects of the quinones on respiration and glycolysis, 

 or on endogenous and glucose respiration, shows that no general rules can 

 be formulated and many factors may be involved. One important factor 

 is the levels of ATP and ADP. Phenanthraquinone at 0.01 mM progres- 

 sively depresses the endogenous respiration of ascites tumor cells, but in 

 the presence of glucose there is some initial stimulation and the respiration 

 then returns to near-normal levels (Tiedemann and Risse, 1960). In cells 

 utilizing glucose the quinone causes a piling up of hexose and triose phos- 

 phates, with a consequent fall of ATP and rise of ADP, the latter account- 

 ing for the acceleration of respiration, while in the absence of glucose this 

 cannot occur, the ATP level is unchanged, and respiration is gradually de- 

 pressed. This mechanism may be involved in the suppression of the Pasteur 

 effect in yeast by thymoquinone (Flaig and de Jong, 1960 b). The ratio 

 of the glucose utilization anaerobically and aerobically, which is near 2 

 in normal yeast, is progressively reduced to almost 1 by increasing concen- 

 trations of thymoquinone. Since 2,4-dinitrophenol also exerts this effect, 

 an uncoupling action by the quinone was considered, but the effects of 

 the two substances on polysaccharide synthesis are different and it is likely 

 that the major action of the quinone is not uncoupling. 



Another important factor in the over-all effects of the quinones on 

 carbohydrate metabolism and respiration is the relative sensitivities of 

 the EM pathway, the lactate or alcohol dehydrogenases, and the enzymes 

 for the disposal of pyruvate. These relationships could be better understood 

 if there were more data on the alterations of keto acid levels occurring 



