7 Synthesis of Phospholipids in Animal Cells

Abstract

Publisher Summary This chapter presents an overview of mammalian phospholipid enzymology. Phosphatidic acid occupies a central position in the biosynthesis of phospholipids and is derived from the acylation of sn -glycerol 3-phosphate or dihydroxyacetone phosphate. In rat liver, sn -glycerol 3-phosphate is generated from the biosynthetic sn -glycerol-3-phosphate dehydrogenase, which reduces dihydroxyacetone phosphate formed during glycolysis and gluconeogenesis. An alternate pathway for generating phosphatidic acid involves the acylation of dihydroxyacetone phosphate. The enzyme utilizes saturated acyl-CoA esters preferentially, producing 1-acyldihydroxyacetone phosphate. Phosphatidic acid is also generated from the ATP-dependent phosphorylation of diacylglycerol catalyzed by diglyceride kinase. Microsomal and cytosolic kinases represent about 30 and 50%, respectively, of the activity detected in crude cell extracts. This enzyme is also reported to associate with microtubules, but the significance of this observation remains obscure. Most of the diacylglycerol utilized for phospholipid synthesis is synthesized de novo from phosphatidic acid. The release of phosphate from phosphatidic acid makes diacylglycerols available for subsequent reaction with choline to form phosphatidylcholine. Strong genetic evidence is available that proves that in cultured cells the majority of phosphatidylcholine is generated through cytidine nucleotides of choline. A CHO cell mutant, detected by its inability to incorporate choline into phospholipid, possesses a thermolabile lesion in CDP-choline synthetase and is unable to generate CDP-choline, dCDP-choline, and phosphatidylcholine under restrictive conditions. Another source of phosphatidylcholine is the S -adenosylmethionine-dependent methylation of phosphatidylethanolamine. Approximately, 20% of liver phosphatidylcholine may be derived in this way but in other tissues and cultured cells, less than 5% arises by methylation.