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The ER synthesizes lipids for building cell membranes and performing cellular functions such as energy storage and signaling. The lipid synthesis machinery embedded in the ER membrane primarily collects all reactants from the cytosol. Following synthesis, the secretory pathway and the ER contact sites distribute these lipids to other cellular organelles. Additionally, the energy-rich triacylglycerides are transported from the ER via lipid droplets.
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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Lipids are an essential component of all biological membranes. The average lipid content in mammalian membranes is 50%, though it can be as low as 20% in the inner mitochondrial membrane or as high as 80% in the myelin sheath present around the nerve cells.
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Defining Substrate Specificities for Lipase and Phospholipase Candidates
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Phospholipase D and Choline Metabolism.

Fredrick O Onono1,2, Andrew J Morris3,4

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Handbook of Experimental Pharmacology
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PubMed
Summary

Phospholipases D (PLDs) generate choline, a vital nutrient essential for cell function and metabolism. This review explores how PLD enzymes and choline generation may be dysregulated in cancer.

Keywords:
CholineOne carbon metabolismPhospholipase D

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Phospholipases D (PLDs) are enzymes that hydrolyze phospholipids, producing phosphatidic acid and a free lipid headgroup.
  • Mammalian PLDs include intracellular PLD1/PLD2 and extracellular enzymes like autotaxin (ENPP2), implicated in cell signaling via lipid products.
  • The biological relevance of the water-soluble product, choline, has been less explored.

Purpose of the Study:

  • To review emerging evidence on the role of choline generation by PLD enzymes.
  • To focus on the potential dysregulation of choline and PLD-dependent processes in cancer.

Main Methods:

  • Literature review of genetic and pharmacological studies on PLD function.
  • Analysis of biochemical pathways involving choline metabolism and phospholipid synthesis.
  • Examination of cancer-related research linking PLDs and choline.

Main Results:

  • PLD1 and PLD2 primarily hydrolyze phosphatidylcholine (PC), while autotaxin acts on lysophospholipids, yielding choline in all cases.
  • Mammals are typically auxotrophic for choline, necessitating dietary intake for acetylcholine synthesis, phospholipid production (PC, SM), and methyl donation in one-carbon metabolism.
  • Emerging evidence suggests a role for choline generation by PLDs in biological functions.

Conclusions:

  • PLD enzymes contribute to cellular signaling not only through lipid products but also via choline generation.
  • Dysregulation of these choline and PLD-dependent processes is a potential factor in cancer development and progression.
  • Further research is warranted to elucidate the precise mechanisms and therapeutic implications.