70 A SYMPOSIUM ON RESPIRATORY ENZYMES 



the end where the iron catalysts are operating but at an earher 

 stage, might be expected under favorable conditions to interrupt 

 respiration without afiFecting the Pasteur reaction. Malonate and 

 maleate, which block the Szent-Gyorgy cycle, might react in this 

 way. Weil-Malherbe (52) has indeed found with maleate poisoning 

 that there is no appreciable aerobic glycolysis in brain when respira- 

 tion has already declined to very low levels. I found, with malonate, 

 similar effects on embryonic heart (74). In Table 9 a survey is given 

 of these and other experiments, where with animal cells a Pasteur 

 effect was found with low respiration. This was observed by Rosen- 

 thal and Lasnitzki (75) with some human cancer without inhibitors 

 and by Kempner and Gaffron (76) with myeloblasts at 6 per cent 

 oxygen pressure. It should be remembered that in Kempner's experi- 

 ments with myeloblasts, while the Pasteur reaction was unaffected, 

 respiration declined with falling oxygen pressure: the Qo^ in 95 per 

 cent oxygen was 8; in 6 per cent oxygen, 3.2. Laser (37) found the 

 reverse with chorion, retina, and mouse liver; that is, little influence 

 of low oxygen tension on respiration but inhibition of the Pasteur 

 reaction. 



Malonate does not have the effect described above on all tissues. 

 I found with pigeon brain a decrease of respiration accompanied 

 by a large increase of aerobic glycolysis (74). Similar results were 

 reported by Kutscher and Sarreither (77) with skeletal muscle. 



Conclusion and Outlook 



It has not been my purpose to give a complete survey of the work 

 in this field. The recent reviews by Burk (83, 84) constitute a com- 

 petent discussion of the problem as a whole, especially with regard 

 to earlier work and thoughts. Our purpose here has been to sum- 

 marize mainly the facts that indicate the occurrence of an oxidative 

 inhibition. In general the evidence may be considered indicative 

 but not conclusive, except in a few instances. The cell may choose 

 to eliminate unneeded anaerobic metabolism by an inhibitory 

 mechanism rather than by a counterforce, but there are indications 

 that such inhibition acts upon reactions directing the internal flow 

 of energy. Substances interrupting the Pasteur linkage likewise in- 

 terrupt synthetic reactions, as has been shown in the case of cysteine 

 (67) and especially dinitrophenol (41). Clifton (78), while in 

 Kluyver's laboratory, made the discovery that dinitrophenol inhibits 

 completely the synthetic processes in microorganisms. His study was 

 based on the work of Barker (85), who demonstrated that with 



