68 II. BIOSYNTHESIS 



acid should be considered as a precursor of liver phospholipids. Likewise, 

 Popjak and Muir^"*^ isolated what they consider to be the precursors of 

 lecithin and cephalin from Ever; these have been identified mainly as 

 a- and /^-glycerophosphates. Moreover, when lecithin or cephalin, labeled 

 with P^2, was injected into rabbits, glycerophosphate, which was isolated 

 from the placenta and liver, had the next highest specific activity after the 

 phospholipids. It may be concluded that glycerophosphate is a pre- 

 cursor of phospholipids, and that this reaction is reversible. Chevallier 

 and Schneider^** also postulated that glycerophosphate is an intermediate 

 in phospholipid synthesis. Finally, there is considerable evidence that 

 enzyme systems exist in animal tissues which can catalyze the combination 

 of fatty acids with glycerophosphate to form phosphatidic acids. ^*^~''*^ 

 In fact, Kornberg and Pricer^*^ reported that L-a-glycerophosphate is 

 esterified by two moles of a higher fatty acid, with a concomitant con- 

 version of two moles of ATP to inorganic pyrophosphate and adenosine-5- 

 phosphate in the presence of a liver enzyme preparation and catalytic 

 amounts of CoA. 



There is considerable evidence that phosphorylcholine is not an inter- 

 mediate in lecithin synthesis. Although Inukai and Nakahara^''^ isolated 

 phosphorylcholine from normal beef liver, it is possible that the appearance 

 of this ester might be attributed to isolation procedures. Riley, **^ on the 

 basis of extensive experiments on rats, was unable to find any evidence 

 that phosphorylcholine is utilized as a unit in phospholipid synthesis; he 

 suggested rather that cephalm, and perhaps lecithin and sphingomyelin, 

 evolve from more labile complex intermediates which are in rapid equilib- 

 rium with simple precursors. Kennedy,*^" also, has presented data which 

 indicate that phosphorylcholine is not an intermediate in lecithin synthesis. 

 When choline-methyl-C^^ was incubated with mitochondria derived from 

 rat liver homogenates, the mitochondrial phospholipid rapidly became 

 radioactive. In contradistinction to these results, no significant incor- 

 poration of phosphorylcholinemethyl-C^* into mitochondrial lecithin oc- 

 curred. Kennedy^^" states that the incorporation of free choline into the 

 lecithin fraction of enzyme granules evidently does not involve phos- 

 phorylcholine. 



3«G. Popjdk and H. Muir, Biochem. J., 45, xi (1949); 46, 103-113 (1950). 



3« A. Chevallier and R. Schneider, Compt. rend. soc. bioL, 146, 1135-1137 (1952). 



3« A. Kornberg and W. E. Pricer, Jr., /. Biol. Chem., 204, 345-357 (1953). 



3« A. Kennedy, Federation Proc, IS, 241 (1954). 



3« R. M. C. Dawson, Biochim. et Biophys. Acta, U, 374-379 (1954). 



3« F. Inukai and W. Nakahara, Proc. Imp. Acad. Tokyo, 11, 260-261 (1935). 



3«R. F. Riley, /. Biol. Chem., 153, 535-549 (1944). 



360 E. P. Kennedy, /. Am. Chem. Soc, 75, 249-250 (1953). 



