70 II. BIOSYNTHESIS 



satisfies the radioactive requirements as the precursor of GPC, and simi- 

 larly Uver phosphatidylethanolamine fulfils the isotopic conditions essen- 

 tial for its function as the precursor of GPE. According to the available 

 evidence, the best theoretical explanation of phosphoHpid synthesis is 

 that glycerophosphate combines with two fatty acid molecules to form the 

 phosphatidic acid before it combines with the nitrogenous base. The last 

 step in the synthesis of phospholipids, therefore, would involve the com- 

 bination of the phosphatidic acid with choline to form lecithin, with etha- 

 nolamine to produce phosphatidylethanolamine (cephalin) , and probably 

 likewise with serine to give rise to phosphatidylserine. Dawson^^^ has 

 interpreted his experimental findings in this manner. 



It is not entirely clear to what extent energy-rich phosphate bonds, as 

 described by Lipmann, are involved in the synthesis of phosphoUpids. 

 Thus, neutral fat (R) might react with phosphate to yield phosphatidic 

 acid, which contains an energy-rich bond (designated as '~), as follows: 



HPO7 + R > R ~ HPO4 



Under these conditions, the addition of choline, ethanolamine, or serine to 

 the phosphatidic acid would complete the phospholipid molecule. The 

 energy required for phosphorylation of lipids under such conditions would 

 be that necessary to provide the energy-rich phosphate bonds. As soon as 

 such compounds were formed, the remaining synthesis could take place 

 spontaneously. In conditions which prevent the generation of high- 

 energy bonds, such as under anaerobic conditions or in the presence of re- 

 spiratory inhibitors, no R '-^ HPO4 is formed, and phosphoHpid synthesis 

 is blocked. 



In a study in vitro of the synthesis of phospholipids from inorganic phos- 

 phate by isolated rat liver mitochondria, Kennedy^^^ noted that a con- 

 tinuance of synthesis required the maintenance of oxidative phosphoryla- 

 tion. The rate of synthesis was found to be approximately doubled by 

 the addition of free glycerol; it is beheved that a-glycerol phosphate is an 

 important intermediate in the synthesis of the phospholipid. Nygaard^*" 

 has hkewise shown that ATP is involved in the condensation of fatty 

 acid and lysolecithin to form lecithin ; the enzymes involved are presumably 

 located in the mitochondria. 



3" E. P. Kennedy, J. Biol. Chem., SOI, 399-412 (1953). 



3M A. P. Nygaard, Arch. Biochem. Biophys., 43, 493-494 (1953). 



