REGULATORY MECHANISMS IN ENERGY METABOLISM 145 



similar cvcle was proposed bv Devlin and Bedell (1960) for mam- 

 malian tissue, using the couple yS-hydroxybutyrate-acetoacetate. 



There is further suggestive evidence that such compartmentation 

 exists in vivo. Thus the experiments by Hoberman (1958) reveal 

 significantlv less utilization" for glycogen svnthesis of the hydrogen 

 of malate and ^-hvdroxybutvrate as compared to that of lactate. 



Further exidence is afforded bv the observation that the ratios 

 of DPNH DPN and TPNHTPN' differ when the soluble fraction 

 and mitochondria are compared (Clock and McLean, 1956; Jacob- 

 son and Kaplan, 1957). 



However, direct evidence is lacking for the compartmentation of 

 other metabolites we need to consider, such as ATP, ADP, AMP, 

 and inorganic phosphate. The argument that the ratio of glucose-1- 

 phoshate /inorganic phosphate is incompatible with glycogen syn- 

 thesis in yeast cells (Trevelyan et ah, 1954), and therefore that in- 

 organic phosphate should be unavailable, is less pertinent now that 

 the uridine pathwav of ghcogen synthesis is known (Leloir et al., 

 1959). This does not mean that such compartmentation does not 

 exist but merelv that sufficient evidence for establishing the fact is 

 lacking. 



Limiting Factors in Glycolysis. It would be logical to assume 

 that the point of regulation of glycolysis is the enzyme which is 

 jate-limiting. Numerous attempts to pinpoint such a site have 

 been unsuccessful largely because the potential rate of the enzymes 

 present exceeds bv far the rate actuallv observed in intact cells 

 (Wu and Racker, i959a; Racker et al, 1960). While this is not al- 

 ways the case (such as in human leukocytes, where glycolysis of 

 intact cells equals glvcolysis of homogenates [Beck, 1958]), it is at 

 the present state of knowledge most likelv that the rate-limiting fac- 

 tors are not the enzvmes themselves but rather the availability of 

 metabolites, 



Pasteur Effect 



We come to the heart of the question: What is the mechanism of 

 the Pasteur effect? The classic review bv Burk ( 1939 ) lists the multi- 

 tude of theories and interpretations which had been given up to that 

 date. A number of other reviews have been published ( Burk, 1937; 

 Dixon, 1937; Lipmann, 1942; Dickens, 1951; Krebs, 1957). One is 

 forced, in reading through the literature, to make a decision on 



