GENERAL METABOLISM iu vitW 91 



choline, has been found to contribute the choHne moiety in the 

 enzymic synthesis of sphingomyeUn by both Hver and brain 

 preparations (Scribney and Kennedy, 1958). Also a similar 

 activation with cytidine triphosphate occurs during the incorpora- 

 tion of ^^P phosphoryl ethanolamine into phosphatidyl ethanol- 

 amine (Kennedy, 1956). 



The phosphatidic acid formed in reaction (4) loses its phosphate 

 group to form an a^-diglyceride and hence the phosphorus of 

 glycerophosphate does not enter the final glycerophosphatide. 

 Although the phosphatidic acid is an intermediate in the synthesis 

 of lecithin, lecithin itself does not become highly radioactive. The 

 reactions governing the introduction of radioactive phosphorus 

 into lecithin (reactions (2), (6) and (9)) are those involved in the 

 synthesis of cytidine diphosphate choline and have not yet been 

 demonstrated in brain, though this is little reason to doubt their 

 occurrence. Establishment of this sequence would assist in 

 understanding why the labelling of phosphorus is markedly less 

 than in the phosphatidic acids, for both phosphates presumably 

 arise from adenosine triphosphate. A plausible explanation would 

 appear to be in terms of a slow turnover of the phosphorylcholine 

 moiety which does not come into equilibrium with the rest of the 

 phosphorus pool during the course of the experiments. Alterna- 

 tively the phosphatidic acids may be part of a separate cyclic 

 process as suggested by Dawson (1955). The rapidity with which 

 phosphatidic acids incorporate radioactive phosphorus is pre- 

 sumably indicative of their rate of synthesis. Steps in this synthesis 

 and subsequent metabolism are fairly well established. Thus 

 glycerol derivatives are known to be precursors of phosphatides in 

 brain tissues (Hokin and Hokin, 1955; Pritchard, 1958) and the 

 participation of D-a^S-diglycerides in the final stages of synthesis of 

 lecithin have been described by Rossiter et al. (1957). The 

 incorporation of palmitate-1-^^C into the phosphatides of cerebral 

 tissues and dispersions was demonstrated by Jedeicken and Wein- 

 house (1954), who also showed that Co A was essential for maximum 

 activity. Attempts to isolate such acyl-CoA derivatives have not 

 been accomplished in brain though the existence of mechanisms 

 involved in their synthesis has been clearly established (see 

 Wolleman and Feuer, 1957). 



The recognition of sequences of the above type in the synthesis 

 of glycerophosphatides, represents a considerable contribution to 



