REGULATORY MECHANISMS IN ENERGY METABOLISM 155 



Crabtree Effect 



The inhibition of endogenous respiration by glycolysis discovered 

 by Crabtree (1929) is often called a reverse Pasteur effect. This is 

 somewhat unfortunate in that this implies functional and mechanistic 

 relationships. This is not necessarilv true. Many hypotheses of the 

 Crabtree effect indeed are based on interrelationships between phos- 

 phate compounds similar to those involved in the Pasteur effect. 

 There are, however, a number of hypotheses divorced from this 

 concept. 



In recent vears the Crabtree effect has received more attention 

 even than the Pasteur effect. This is not surprising since it is a 

 phenomenon generally associated with malignant cells. It is found 

 in a varietv of tumors (Krah, 1930; Elliot and Baker, 1935; Victor 

 and Potter, 1935; Burk et al, 1941; Kun et al, 1951; McKee et al, 

 1953 ) . The high aerobic glvcolvsis exhibited bv such cells is a gen- 

 eral but not absolutelv distinguishing characteristic. It is often said 

 that such high glvcolvsis is evidence that the Pasteur effect is lacking 

 in tumor cells (cf. Acs et al, 1955). This is not necessarily true. 

 Some tumor cells exhibit both a Crabtree and a Pasteur effect. 

 Ascites tumor cells are the classic example. Also the Crabtree effect 

 is not limited to tumor cells. It has been found in renal papillae 

 and bovine cartilage (Rosenthal et al., 1940), bull spermatozoa 

 (Lardy and Phillips, 1941), leukocytes (McKinney et al, 1953; 

 Martin et al, 1955), retinal cells (Cohen, 1957), and in TetraJujmena 

 ( Warnock and van Eys, unpublished observations ) . 



The observation that both Crabtree and Pasteur effects can be 

 present together or either one alone is sufficient indication that the 

 two phenomena are separate problems. The Crabtree effect, just as 

 did the Pasteur effect, elicited three main theories as to its cause: 

 (a) competition between respiration and glycolysis for phosphate 

 metabolites, (b) enhanced operation of the hexose monophosphate 

 shunt due to the addition of carbohydrate, and (c) variation in 

 hvdrogen ion concentration. 



ComiJetition for Phosphorylated Intermediates. Since we are 

 dealing in the Crabtree effect with induced variations in respiration, 

 it is of vital importance to know what the pacemaker of respira- 

 tion is. The extensive evidence accumulated on this subject deserves 

 more than the mention which can be given here, but it is sufficient 



