EFFECTS OF MALONATE ON GLUCOSE METABOLISM 133 



the metabolic characteristics of tissues, would change with age and that 

 this would be reflected in difl"erent susceptiblies to inhibitors. The altered 

 response to inhibitors could provide some information on the nature of 

 metabolic aging. The results obtained on rat brain are, however, discordant. 

 Tyler (1942), using a minced preparation, found that malonate inhibition 

 of the respiration in the presence of glucose increases up to a rat age of 10 

 days, after which it remains at the adult level (see accompanying tabula- 

 tion). Although the control respiration rises, the malonate-resistant fraction 



of the respiration remains constant up to 10 days, i.e., the increased respi- 

 ration is all due to the development of activation of a system sensitive to 

 malonate, presumably the cycle. On the other hand, Muir et al. (1959) 

 reported that the glucose respiration of adult rat brain slices is less sensitive 

 to 10 inM malonate (30% inhibition) than the respiration of tissue from 

 young animals of 1-3 days (70%). In this case, the young brain respires 

 almost 2.5 times as rapidly as adult brain. The differences in these obser- 

 vations may be related to the preparations used (mince or slice). There are 

 several reasons why malonate sensitivity would change with age, for exam- 

 ple, an alteration of cycle activity, the development or loss of pathways 

 other than the cycle for the metabolism of acetyl-CoA, or a change in the 

 ability to demonstrate a Pasteur effect. The effect of age should also be 

 studied on the electrically stimulated or K+-stimulated respiration of the 

 brain, since it is more sensitive to malonate and the results might have 

 more physiological pertinence. 



The respiratory rates and patterns of fungus spores are altered during 

 the initiation of germination and the subsequent development of the germ 

 tube (Gottlieb, 1964). During the incubation of the spores of Penicillium 

 oxalicum and Ustilago maydis and the progress of germination, the respira- 

 tion in the presence of glucose rises markedly and this is accompanied by an 

 increasing sensitivity to malonate (see accompanying tabulation) (Caltrider 

 and Gottlieb, 1963). It is somewhat difficult to determine if this implies 



