Polyunsaturated Docosahexaenoic vs Docosapentaenoic AcidDifferences in Lipid Matrix Properties from the Loss of One Double Bond

Abstract

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.

Reduced G Protein-coupled Signaling Efficiency in Retinal Rod Outer Segments in Response to n-3 Fatty Acid Deficiency

“…Differences in acyl chain packing between membranes containing DHA and DPA phospholipids have been demonstrated by several physical techniques. NMR demonstrates that the DHA-containing phospholipids are more flexible at the methyl end of the chain and undergo more rapid conformational changes than DPA-containing phospholipids (28). Timeresolved fluorescence measurements on the ROS membrane preparations used in the current experiments also show a higher degree of acyl chain order in the n-3 FA-deficient, DPAcontaining ROS membranes relative to the n-3 FA-adequate, DHA-containing ROS membranes.…”

Docosahexaenoic acid affects cell signaling by altering lipid rafts

“…In agreement, on the basis of 2 H NMR order parameters measured for the perdeuterated stearoyl sn-1 chain in PCs it was inferred that the thickness of the bilayer is about the same with DHA as stearic acid (18 carbons) at the sn-2 position [45]. A wedge shape becoming slightly fatter at the center of the hetroacid saturated-polyunsaturated bilayer is indicated for the saturated chain while, conversely, the DHA chain occupies an inverted wedge shape with higher volume density near the aqueous interface [46]. The origin is the tremendously flexible structure of DHA undergoing rapid inter-conversions between many torsional states such that the terminal methyl end often approaches the membrane surface [47][48][49].…”

The location and behavior of α‐tocopherol in membranes

“…DHA chains isomerize so rapidly that they explore their entire conformational space within 50 ns [66]. The torsional states adopted include bent conformations that would bring even the lower portions of the PUFA chain up to the membrane surface [67][68][69] and into the vicinity of the chromanol group, which is also well situated for regeneration of the tocopheroxyl radical by water-soluble reducing agents including ascorbate.…”