Substrate channeling in the glycerol-3-phosphate pathway regulates the synthesis, storage and secretion of glycerolipids

Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Jan;1865(1):158438. doi: 10.1016/j.bbalip.2019.03.010. Epub 2019 Apr 5.

Abstract

The successive acylation of glycerol-3-phosphate (G3P) by glycerol-3-phosphate acyltransferases and acylglycerol-3-phosphate acyltransferases produces phosphatidic acid (PA), a precursor for CDP-diacylglycerol-dependent phospholipid synthesis. PA is further dephosphorylated by LIPINs to produce diacylglycerol (DG), a substrate for the synthesis of triglyceride (TG) by DG acyltransferases and a precursor for phospholipid synthesis via the CDP-choline and CDP-ethanolamine (Kennedy) pathways. The channeling of fatty acids into TG for storage in lipid droplets and secretion in lipoproteins or phospholipids for membrane biogenesis is dependent on isoform expression, activity and localization of G3P pathway enzymes, as well as dietary and hormonal and tissue-specific factors. Here, we review the mechanisms that control partitioning of substrates into lipid products of the G3P pathway.

Keywords: Fatty acid; Glycerol-3-phosphate pathway; Lipid droplet; Phospholipids; Substrate channeling; Triacylglycerol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acylation
  • Animals
  • Fatty Acids / metabolism
  • Glycerol-3-Phosphate O-Acyltransferase / metabolism*
  • Glycerophosphates / metabolism*
  • Glycerophospholipids / metabolism*
  • Humans
  • Lipid Droplets / metabolism
  • Lipogenesis*
  • Signal Transduction*
  • Triglycerides / metabolism

Substances

  • Fatty Acids
  • Glycerophosphates
  • Glycerophospholipids
  • Triglycerides
  • alpha-glycerophosphoric acid
  • Glycerol-3-Phosphate O-Acyltransferase

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