158 CONTROL MECHANISMS IN CELLULAR PROCESSES 



regulating constituent. The short-term Crabtree effect observed and 

 described by Chance and Hess appears to indicate compartmentation 

 of ATP. The intense inhibition of respiration after the addition of 

 glucose is paralleled by an equally intense inhibition of glucose up- 

 take ( Chance and Hess, 1956 ) . However, if this compartmentation 

 is only through the rate of diffusion of ATP out of the mitochondria 

 rather than through absolute compartmentation, it is not certain 

 whether this mechanism is the explanation of the Crabtree effect 

 seen in experiments of one hour or longer duration. It does not 

 explain either the observation by Kunz and Schmidt (1957) that 

 during the intense inhibition the total adenine nucleotide level drops 

 to low levels. However, this was not seen by Ibsen et al. (1958). 

 An alternative explanation of such ATP and ADP compartmenta- 

 tion was offered by Ibsen et al. ( 1958 ) . These workers suggested 

 that, if the diffusion of ATP or ADP through the mitochondrial mem- 

 brane requires the adenylate kinase system, the extent of unavail- 

 ability of nucleotides may be dependent on the proper levels of all 

 three compounds: AMP, ADP, and ATP. 



Stimulation of the Hexose Monophosphate Shunt. Seelich and 

 Letnansky (1960) proposed a theory, based on the stimulation of 

 the hexose monophosphate shunt. They reason that the endogenous 

 substrate in ascites cells is non-carbohydrate. Therefore, since it is 

 known that the shunt stimulates lipid synthesis, a competition be- 

 tween lipid anabolism and catabolism arises, resulting in lowered 

 respiration. This would explain the lack of effect of iodoacetate. In 

 fact, in the presence of iodoacetate they found that the respiration 

 is nearly malonate independent and thus represents mainly shunt 

 oxidation. 



They assume that the Crabtree effect of 2-deoxyglucose indicates 

 that this sugar does result in TPNH formation.*^ Furthermore, in 

 ascites cells glucosamine is converted rapidly to glucose-6-phosphate 

 (Merker et al., 1960b). A more serious objection that the effect is 

 not alleviated by switching to carbohydrate substrates, such as pyru- 

 vate, is explained by the assumption that pyruvate is reduced to 

 lactate due to the formed TPNH. Thus pyruvate would not be a 

 substrate for respiration. That glucose does not inhibit acetate 



6 In this respect it is interesting that in brain homogenates, which glycolyze in the 

 presence of 2-deoxyghicose, not all the utilized 2-deoxyglucose can be accounted for 

 as 2-deoxyglucose-6-phosphate (J. van Eys and W. Hill, unpublished observations). 



