Phospholipid Synthesis

Phospholipids are synthesized by esterification of an alcohol to the phosphate of phosphatidic acid (1,2-diacylglycerol 3-phosphate). Most phospholipids have a saturated fatty acid on C-1 and an unsaturated fatty acid on C-2 of the glycerol backbone. The most commonly added alcohols (serine, ethanolamine and choline) also contain nitrogen that may be positively charged, whereas, glycerol and inositol do not.


1. glycerol phosphate
dehydrogenase
2. glycerol kinase
3. acyl transferase

The last product, 1,2-diacylglycerol-3-phosphate, is also known as phosphatidic acid, and its phospholipid derivatives are phosphatidyl-X

Phospholipid Synthesis
Phospholipids can be synthesized by two mechanisms. One utilizes a ( Cytidine 5-diphosphate)CDP-activated polar head group for attachment to the phosphate of phosphatidic acid. The other utilizes CDP-activated 1,2-diacylglycerol and an inactivated polar head group.
PC: This class of phospholipids is also called the lecithin s. Choline is activated first by phosphorylation and then by coupling to CDP prior to attachment to phosphatidic acid. PC is also synthesized by the addition of choline to CDP-activated 1,2-diacylglycerol. A third pathway to PC synthesis, involves the conversion of either PS or PE to PC.
PE: Synthesis of PE can occur by two pathways. The first requires that ethanolamine be activated by phosphorylation and then by coupling to CDP. The ethanolamine is then transferred from CDP-ethanolamine to phosphatidic acid to yield PE. The second involves the decarboxylation of PS.
PS: The pathway for PS synthesis involves an exchange reaction of serine for ethanolamine in PE. This exchange occurs when PE is in the lipid bilayer of the a membrane. As indicated above, PS can serve as a source of PE through a decarboxylation reaction.
PI: The synthesis of PI involves CDP-activated 1,2-diacylglycerol condensation with myo-inositol. One polyphosphoinositide is a critically important membrane phospholipid involved in the transmission of signals for cell growth and differentiation from outside the cell to inside.
PG: These molecules are found in high concentration in mitochondrial membranes and as components of pulmonary surfactant. Phosphatidylglycerol also is a precursor for the synthesis of cardiolipin.
DPG: These molecules are very acidic. They are found primarily in the inner mitochondrial membrane and also as components of pulmonary surfactant. One important class of diphosphatidylglycerols is the cardiolipins. These molecules are synthesized by the condensation of CDP-diacylglycerol with PG.