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Related Concept Videos

Lipids as Anchors01:32

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In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
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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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Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
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Bile Acid Recognition by NAPE-PLD.

Eleonora Margheritis1, Beatrice Castellani2, Paola Magotti2

  • 1Center for Nanotechnology Innovation@NEST, Istituto Italiano di Tecnologia , Piazza San Silvestro 12, 56127 Pisa, Italy.

ACS Chemical Biology
|August 30, 2016
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Bile acids regulate the N-acyl phosphatidylethanolamine specific-phospholipase D (NAPE-PLD) enzyme, which produces key signaling lipids. Specific bile acids activate NAPE-PLD, increasing its activity and altering protein stiffness.

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Area of Science:

  • Biochemistry
  • Enzymology
  • Molecular Biology

Background:

  • N-acyl phosphatidylethanolamine specific-phospholipase D (NAPE-PLD) synthesizes endogenous cannabinoids and other lipid mediators.
  • These lipids are crucial for physiological processes like stress, pain, appetite, and lifespan.
  • Previous work elucidated the crystal structure of human NAPE-PLD, identifying bile acid binding sites.

Purpose of the Study:

  • To investigate the allosteric regulation of NAPE-PLD by bile acids.
  • To determine how bile acid structure influences NAPE-PLD activity and protein dynamics.

Main Methods:

  • Elastic neutron scattering to measure protein stiffness.
  • Enzyme kinetics assays to quantify NAPE-PLD catalytic activity with different substrates.
  • Bile acid binding affinity measurements.

Main Results:

  • Deoxycholic acid binding increases NAPE-PLD stiffness and enhances catalytic activity by approximately 7-fold for unsaturated substrates.
  • Other dihydroxy bile acids (chenodeoxycholic acid, conjugates) also activate NAPE-PLD.
  • Lithocholic acid, a monohydroxy bile acid, acts as a reversible inhibitor.

Conclusions:

  • Bile acids act as allosteric cofactors for NAPE-PLD, modulating its enzymatic function.
  • NAPE-PLD's response is sensitive to the number and position of hydroxyl groups on the bile acid molecule.
  • This study reveals a novel mechanism of enzyme regulation by bile acids, impacting lipid signaling pathways.