106 FACTORS AFFECTING METABOLISM in vitrO 



From the data presented these latter appear to be 0-5 jumoles/g 

 wet wt. (cf. Table 12). Oxygen uptake by slices metabolizing 

 fructose at 10 mM was similar to that when glucose was the 

 substrate and it was suggested that this, together with the lowered 

 lactic acid production and levels of adenosine triphosphate, 

 indicated that fructose was metabolized by a route differing from 

 glucose, leading to a lowered extent of phosphate exchange. At 

 present it seems unnecessary to consider such differences in terms 

 of differing metabolic routes for the substrates rather than as the 

 balance between energy requirement and production. Glycolysis, 

 as normally measured, is artificial in the sense that the lactic acid 

 measured is that passing from the slice to the medium, the final 

 quantity reached depending largely upon the ratio of the volume 

 of the slice to the volume of the medium (Rodnight and Mcllwain, 

 1954) and upon the extent to which pyruvate may be preferentially 

 oxidized (cf. Heald, 1953; Mcllwain, 19536). 



Study with disintegrated preparations has shown that with 

 aqueous dispersions of rat brain, glucose, fructose- 1 : 6-diphos- 

 phate, and mannose were effective in supporting the incorporation 

 of radioactive phosphate into the phospholipids whilst galactose, 

 citrate, malate, and succinate, though supporting oxygen uptake 

 were not effective (McMurray et al., 1957), results similar to those 

 found with the intact slice. In this system labelling was correlated 

 with the ability to support glycolytic phosphorylation. In disper- 

 sions where phosphorylation was predominantly oxidative 

 (Dawson, 1953; McMurray et ai, 1957) pyruvate, succinate, 

 fumarate, glutamate, malate, citrate and a-oxoglutarate supported 

 an active incorporation of phosphate into the phospholipids 

 whereas glucose was ineffective. 



Whether or not a substrate supports incorporation of radioactive 

 phosphate in vitro into phosphates such as the phospholipids thus 

 seems to be dependent largely upon the type of preparation used. 

 In disintegrated preparations, the primary factor is the ability to 

 form energy-rich phosphates. In the intact slice the ability to 

 maintain levels of these phosphates comparable to those maintained 

 by glucose appears to be essential. It is likely that the inability of 

 other substrates to be as effective as glucose is related to the extent 

 to which the energy released on oxidation is able to meet the energy 

 requirements of the tissue. It seems noteworthy that glucose, 

 which is the major substrate supporting function in vivo is the 



