Membrane phospholipid biosynthesis from glycerol-3-phosphate via phosphatidic acid (PA) intermediate. PA → diacylglycerol (DAG; also a signaling molecule, see inositol_phosphate_signaling) → choline/ethanolamine/serine/inositol head-group attachment (Kennedy pathway: CDP-choline / CDP-ethanolamine activation). PEMT (phosphatidylethanolamine N-methyltransferase, hepatic) provides ~30% of phosphatidylcholine via 3 sequential methylations from SAM. Choline supplementation (alpha-GPC, citicoline) feeds the Kennedy pathway. Phospholipid imbalance (low PC/PE ratio) is associated with NAFLD progression. Lysophosphatidylcholine + lysophosphatidic acid are bioactive lipid mediators.
Organ Systems
endocrine
nervous
Pathway Steps
glycerol-3-phosphate → phosphatidic-acid — via GPAT + AGPAT (acyl-CoA donor). Sequential acylation (GPAT, AGPAT) of glycerol-3-phosphate builds phosphatidic acid — the common precursor of all glycerophospholipids and of triacylglycerol, and itself a signaling lipid; the branch point between membrane phospholipid and fat storage.
phosphatidic-acid → diacylglycerol — via PA phosphatase (lipin-1). Phosphatidic-acid phosphatase (lipin-1) makes DAG, both a triglyceride precursor and a PKC-activating signaling lipid. Lipin-1 mutations cause recurrent rhabdomyolysis; this PA↔DAG node governs the lipogenesis-vs-signaling split.
diacylglycerol → phosphatidylcholine — via Kennedy pathway: CDP-choline + DAG → PC (CPT). The CDP-choline (Kennedy) pathway makes phosphatidylcholine, the most abundant membrane phospholipid, from choline — linking choline status to membrane integrity and to hepatic VLDL secretion (PC is required to package and export fat).
phosphatidylethanolamine → phosphatidylcholine — via PEMT — hepatic; 3 sequential SAM methylations; ~30% of PC pool. PEMT methylates phosphatidylethanolamine to PC via three SAM methylations — a hepatic route supplying ~30% of PC and a large methyl-group consumer. It lets the liver make PC when dietary choline is low, but PEMT variants/estrogen-dependence make choline conditionally essential in some.