Biosynthesis of precursors: phosphatidic acid and diacylglycerol (DAG)
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Figure 26.1 Structure of the major phospholipids of animal cell membranes. DPG, diphosphatidylglycerol; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PI, phosphatidylinositol; PS, phosphatidylserine. |
All animal cells, except for erythrocytes, are able to synthesize phospholipids de novo, whereas triglyceride synthesis occurs mainly in liver, adipose tissue, and intestinal cells. As shown in Figure 26.2, phosphatidic acid and 1,2-DAG are common intermediates in the synthesis of both triacylglycerols and phospholipids. Glycerol-3-phosphate is the primary starting material for synthesis of phosphatidic acid;
it is formed in most tissues by reduction of the glycolytic intermediate, dihydroxyacetone phosphate (DHAP). In liver, kidney, and intestine, glycerol-3-P can also be formed directly via phosphorylation of glycerol by a specific kinase.
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Glycerol-3-P is acylated by transfer of two long-chain fatty acids from fatty acyl-CoA to the hydroxyl groups at carbons 1 and 2, producing phosphatidic acid. The first fatty acid - usually a saturated fatty acid - is added to carbon-1, forming lysophosphatidic acid; the prefix 'lyso' indicates that one of the hydroxyl groups is not acylated. Then, a second fatty acid - usually an unsaturated fatty acid - is added to carbon-2 to form phosphatidic acid. DHAP may also be acylated by addition of a fatty acid to the 1-hydroxyl group, and this intermediate is then reduced and acylated to phosphatidic acid. Phosphatidic acid is converted to DAG by a specific cytosolic phosphatase.
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