Polyunsaturated Docosahexaenoic vs Docosapentaenoic Acid-Differences in Lipid Matrix Properties From the Loss of One Double Bond

J Am Chem Soc. 2003 May 28;125(21):6409-21. doi: 10.1021/ja029029o.


Insufficient supply to the developing brain of docosahexaenoic acid (22:6n3, DHA), or its omega-3 fatty acid precursors, results in replacement of DHA with docosapentaenoic acid (22:5n6, DPA), an omega-6 fatty acid that is lacking a double bond near the chain's methyl end. We investigated membranes of 1-stearoyl(d(35))-2-docosahexaenoyl-sn-glycero-3-phosphocholine and 1-stearoyl(d(35))-2-docosapentaenoyl-sn-glycero-3-phosphocholine by solid-state NMR, X-ray diffraction, and molecular dynamics simulations to determine if the loss of this double bond alters membrane physical properties. The low order parameters of polyunsaturated chains and the NMR relaxation data indicate that both DHA and DPA undergo rapid conformational transitions with correlation times of the order of nanoseconds at carbon atom C(2) and of picoseconds near the terminal methyl group. However, there are important differences between DHA- and DPA-containing lipids: the DHA chain with one additional double bond is more flexible at the methyl end and isomerizes with shorter correlation times. Furthermore, the stearic acid paired with the DHA in mixed-chain lipids has lower order, in particular in the middle of the chain near carbons C(10)(-)(12), indicating differences in the packing of hydrocarbon chains. Such differences are also reflected in the electron density profiles of the bilayers and in the simulation results. The DHA chain has a higher density near the lipid-water interface, whereas the density of the stearic acid chain is higher in the bilayer center. The loss of a single double bond from DHA to DPA results in a more even distribution of chain densities along the bilayer normal. We propose that the function of integral membrane proteins such as rhodopsin is sensitive to such a redistribution.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Computer Simulation
  • Docosahexaenoic Acids / chemistry*
  • Fatty Acids, Unsaturated / chemistry*
  • Fourier Analysis
  • Lipid Bilayers / chemistry*
  • Membranes, Artificial
  • Molecular Conformation
  • Nuclear Magnetic Resonance, Biomolecular
  • Structure-Activity Relationship
  • Thermodynamics
  • X-Ray Diffraction


  • Fatty Acids, Unsaturated
  • Lipid Bilayers
  • Membranes, Artificial
  • Docosahexaenoic Acids
  • docosapentaenoic acid