IV PHOSPHOLIPID BIOSYNTHESIS IO7 



2. The enzymatic synthesis of lecithin and kephalin 



The enzymatic synthesis of lecithin and kephaUn has been clarified by recent 

 experiments from the laboratories of Kornberg and of Kennedy. Cytidine diphos- 

 phocholine (CDP-chohne) and cytidine diphosphoethanolamine (CDP-ethanol- 

 amine) function as coenzymes in the process. The condensation of these "activated" 

 forms of choline and ethanolamine with a,p-diglycerides are the final steps in 

 phosphatide synthesis (Kennedy and Weiss, 1955, 1956). 



[a) CD P-choline formation 



Phosphorylcholine and pliosphorylethanolamine occur in the acid soluble extracts 

 of a variety of tissues. The formation of these compounds from the free bases has 

 been demonstrated in yeast and animal tissues (Wittenberg and Kornberg, 1953). 



i) Choline (ethanolamine) + ATP -* phosphorylcholine (phosphoryl-ethanolamine) 



+ ADP 



Phosphorylcholine doubly labelled with ^^P and ^'*C is incoiporated into the 

 phospholipids of liver mitochondria with practically unaltered ratios of the isotopes 

 (Kornberg, 1954). Enzymes which carry out the synthesis of CDP-choline and 

 CDP-ethanolamine from phosphorylcholine and phosphorylethanolamine are 

 also widely distributed in nature. 



2) CTP + phosphorylcholine - — . CDP choline + PP 



3) CTP + phosphorylethanolamine ^ » CDP ethanolamine — PP 



CDP-choline next reacts with a,p-diglycerides to form lecithin: 



PC-cytidyl transferase 



4) CDP choline + a. P-diglyceride ' lecithin + CMP 



An analogous reaction occurs with CDP-ethanolamine. 



PE-cytidyl transferase 



5) CDP-ethanolamine + a, [i-diglyceride ^ ' phosphatidyl ethanol-amine + CMP 



The CMP which is formed in reactions 4) and 5) can be rephosphorylated to CTP at 

 the expense of ATP in reactions catalyzed by enzymes which occur in the cytoplasm 

 of tissues (Herbert and Potter, 1956). 



{b) Phosphaticlic acid formation 



The a, [3-digIyceride is probably formed by the dephosphorylation of phosphatidic acid, 

 a substance which is present in fairly high concentration in plant tissues (Kornberg, 1954; 

 Kennedy and Weiss, 1956). Phosphatidic acid is in turn formed as follows (Kornberg and 

 Pricer, 1953a, b) : 



6) Fatty acids + ATP + coenzyme A -* fatty acyl-CoA + AMP + PP 



7) 2 Fatty acyl-CoA + a-glycerol phosphate -^ phosphatidic acid + CoA 



The role of a-glycerolphosphate as an intermediate in phospholipid synthesis is supported 

 by the following evidence. The incorporation of H3-^-P04 into phospholipides of liver 

 mitochondria is accelerated by glycerol but inhibited by non-labelled a-glycerol phosphate 



Literature p. 124 



