144 CONTROL MECHANISMS IN CELLULAR PROCESSES 



A third point of question on the Embden-Meyerhof pathway is 

 the presence of a TPNH catalyzed reduction of pyruvate. This ac- 

 tivity exists in corneal epithelium (Kinoshita, 1957), liver (Navazio 

 et al., 1957), brain (Potter and Niemeyer, 1959), and virus infected 

 chorioallantoic membranes ( Kun et al., 1960 ) . It appears possible, 

 especially in the latter instance, that two separate dehvdrogenases 

 are involved. Thus, this constitutes a second source of lactic acid 

 not directly on the classic Embden-Meyerhof pathway. It is pos- 

 sible, however, that the "normal" lactic dehydrogenase could cata- 

 lyze the reaction (Holzer and Schneider, 1958). In either case, 

 since the observation has been made that DPN inhibits the utili- 

 zation of TPNH, low DPN levels are required for the reaction to 

 proceed (Kun et al., I960; Navazio et al., 1957). Normally this is 

 probably not the case, but such conditions could be provoked bv 

 experimental design. 



Cellular Organization and Compartmentation. Many studies on 

 the Pasteur effect, and recently on the Crabtree effect, are now per- 

 formed on homogenates, rather than whole cells. It is becoming 

 increasingly clear that cellular organization and compartmentation 

 of enzymes and substrates play an important role in maintaining 

 normal metabolism, even in the absence of hormonal influences. 

 That enzymes are localized in specific fractions of the cell is well 

 known, but recently the concept has grown that the compartmenta- 

 tion of metabolites is important. In fact, a varietv of explanations 

 of the Pasteur and Crabtree effects are based on this phenomenon. 



The evidence for such compartmentation of metabolites should 

 be examined. Reduced and oxidized pyridine nucleotides definitelv 

 appear to be compartmentized. Carefully prepared mitochondria 

 from a variety of sources will not oxidize DPNH. This was first re- 

 ported by Lehninger ( 1955 ) and further elaborated upon by Biicher 

 and Klingenberg (1958). To accomplish oxidation of DPNH by 

 mitochondria an external pathway is necessary. This can be fur- 

 nished either by microsomal cytochrome-c-reductase (Lehninger, 

 1955) or by a coupled action of a pair of soluble and insoluble de- 

 h\'drogenases. Such a pathway was first suggested by Biicher 

 (Biicher and Klingenberg, 1958; Zebe et al., 1959) and by Estabrook 

 and Sacktor (1958). Originally this glycerol-1-phosphate cycle was 

 proposed for insect flight muscle, but there is no reason to believe 

 that such a cycle should be limited to insects ( Zebe et al., 1959 ) . A 



