Biosynthesis of Membrane Phospholipids:- Cells Have Two Strategies for Attaching Phospholipid Head Groups
The first steps of glycerophospholipid synthesis are shared with the pathway to triacylglycerols (Fig. 21–17): two fatty acyl groups are esterified to C-1 and C-2 of L-glycerol 3-phosphate to form phosphatidic acid. Commonly but not invariably, the fatty acid at C-1 is saturated and that at C-2 is unsaturated. A second route to phosphatidic acid is the phosphorylation of a diacyl glycerol by a specific kinase.
The polar head group of glycerophospholipids is at tached through a phosphodiester bond, in which each of two alcohol hydroxyls (one on the polar head group and one on C-3 of glycerol) forms an ester with phosphoric acid (Fig. 21–23). In the biosynthetic process, one of the hydroxyls is first activated by attachment of a nucleotide, cytidine diphosphate (CDP). Cytidine monophosphate (CMP) is then displaced in a nucleophilic attack by the other hydroxyl (Fig. 21–24). The CDP is attached either to the diacylglycerol, forming the activated phosphatidic acid CDP-diacylglycerol (strategy 1), or to the hydroxyl of the head group (strategy 2). Eukaryotic cells employ both strategies, whereas prokaryotes use only the first. The central importance of cytidine nucleotides in lipid biosynthesis was discovered by Eugene P. Kennedyin the early 1960s.
FIGURE 21–23 Head-group attachment. The phospholipid head group is attached to a diacylglycerol by a phospho diester bond, formed when phosphoric acid condenses with two alcohols, eliminating two molecules of H2O.
FIGURE 21–24 Two general strategies for forming the phosphodiester bond of phospholipids. In both cases, CDP supplies the phosphate group of the phosphodiester bond.
