160 CONTROL MECHANISMS IN CELLULAR PROCESSES 



The fact that extra hexokinase enhanced the effect, and that gkicose- 

 6- phosphate did not eHcit the Crabtree effect, pmpointed to the 

 phosphorylation step as the point of interest. In ahnost all cases 

 the Crabtree effect could be traced to pH effects in the homogenate. 

 In fact, the initial pH of the homogenate determined whether a 

 Crabtree effect was present. 



The addition of an equivalent amount of brain mitochondria 

 (calculated per unit homogenate) to a tumor supernatant gave a 

 homogenate in which the effect was absent. Tumor mitochondria 

 with brain supernatant, on the other hand, gave a preparation which 

 does show a Crabtree effect. However, a brain homogenate could 

 show a Crabtree effect by lowering the activity of mitochondria 

 either by removing part of the mitochondria or by their partial in- 

 hibition with amytal ( Cereijo-Santalo and Park, 1960). 



This is consistent with the multitude of sugars which can provoke 

 a Crabtree effect, and explains why tumor homogenates and homog- 

 enates with high glycolytic rates (Lugenova et ah, 1957) show a 

 Crabtree effect. The major deficiency in tumors is not impaired 

 mitochondria but fewer mitochondria per unit tissue (Schneider and 

 Hogeboom, 1950). In fact, raising the amount of tumor mitochon- 

 dria abolished the Crabtree effect in tumor homogenates. This ex- 

 planation is not valid in the reconstructed system of Racker (Gatt 

 and Racker, 1959a). Whether this explanation is correct for the 

 whole cell remains to be seen. 



The Significance of Crabtree and Pasteur Effects 



It was mentioned before that the Pasteur effect is teleologically 

 reasonable. This tends to persuade one to regard it as a true regu- 

 latory process. On the other hand, the Crabtree effect is only as- 

 sociated with those cells which have aerobic lactate formation. This 

 is generally regarded as a major tumor characteristic. From the ex- 

 periments of Cereijo-Santalo, it is suggested that this may be the 

 result of a quantitative difference rather than a qualitative one. It 

 is therefore possible that the Crabtree effect is an expression of the 

 properties of abnormal cells; an effect which one could call a bio- 

 logical artifact. 



The Pasteur effect may have further implications, however. 

 There are indications that glycolysis has functions above and be- 

 yond its pyruvate-donating powers. Recent studies with oxamic 



