Influence of the Positions of cis Double Bonds in the sn-2-Acyl Chain of Phosphatidylethanolamine on the Bilayer's Melting Behavior

Abstract

In an attempt to examine the effects of different numbers and positions of cis double bonds in the sn-2-acyl chain of phosphatidylethanolamine (PE) on the bilayer's melting behavior, 21 molecular species of PE were first semisynthesized, and their T m and ⌬H values were subsequently determined by high resolution differential scanning calorimetry. In the plot of T m versus the number of the cis double bond, some characteristic profiles were observed for the various series of PEs. In recent years, there has been increasing evidence suggesting the existence of a close correlation between some vital functions of cells and the various degrees of unsaturation in the sn-2-acyl chains of membrane phospholipids (1-3). Consequently, detailed and systematic investigation of the properties of sn-1-saturated/sn-2-unsaturated phospholipids in the organized membrane structure such as the lipid bilayer should be recognized and pursued. Furthermore, now is the time for studying unsaturated phospholipids, since sophisticated computer-based molecular modeling techniques from the hardware and the software fields have come together to provide valuable structural and energetic information about self-assembled biomolecules within a reasonable time frame. Results obtained with experimental and modeling studies of sn-1-saturated/sn-2-unsaturated phospholipids could eventually help illuminate the specific roles played by various natural phospholipids in many membrane-related cell functions or diseases.The first detailed and systematic studies of the thermotropic phase behavior of phospholipids containing various numbers of cis double bonds in their sn-2-acyl chains were performed by Keough and co-workers (4 -6). By using two series of phosphatidylcholines (PCs) 1 and by applying the differential scanning calorimetry (DSC) techniques, they have shown that the introduction of a cis double bond into the sn-2-acyl chain at or near the center of the chain has a marked reducing effect on the phase transition temperature (T m ) associated with the gel-toliquid crystalline phase transition of the lipid bilayer. A second cis double bond incorporated at the methylene-interrupted position toward the methyl end also reduces the T m , but by a smaller amount. Interestingly, the introduction of a third cis double bond between the second cis double bond and the methyl end can cause a slight increase in T m . This calorimetric work has been confirmed more or less by other investigators using PCs with different chain lengths (7,8).Recently, we have studied systematically the effect of different positions of single cis double bond in the sn-2-acyl chain on the phase transition behavior of lipid bilayers composed of sn-1 saturated/sn-2-monounsaturated PCs or phosphatidylethanolamines (PEs) by high resolution DSC and computer-based molecular mechanics (MM) simulations (9 -11). The position of the single cis double bond (⌬ n ) is found in both lipid classes to exert a characteristic influence on the gel-to-liquid crystalline

Effects of Various Numbers and Positions of cisDouble Bonds in the sn-2 Acyl Chain of Phosphatidylethanolamine on the Chain-melting Temperature

“…In particular, the lipid species with an sn-2 arachidonyl (or allcis- 5,8,11,14-eicosatetraenoyl) chain has the smallest T m value of 6.6°C. It should be mentioned that the phase transition behavior of C (20):C(20)PE and some of its 6-unsaturated derivatives has been reported recently from this laboratory (8). However, the recently reported DSC thermograms were incomplete; for instance, the one displayed by the aqueous dispersion of C (20):C(20:1⌬ 14 )PE was missing.…”

“…Mixed-chain sn-1 C 20 -saturated/sn-2 C 20 -unsaturated PE was semisynthesized from the corresponding PC by the base-exchange reaction in the presence of excessive amounts of ethanolamine hydrochloride, at pH 5.6, using phospholipase D according to the method of Comfurius and Zwaal (14) as described in detail elsewhere (6,8). The semi-synthesis of mixed-chain PC involved the acylation of C(20)-lysophosphatidylcholine with C 20 fatty acid in the presence of catalyst 4-pyrrolidinopyridine using the established procedure reported previously (15).…”

“…These four; not five lipid species share a common segment of 5 consecutive methylene units, extending from C(3) to C(7), in the sn-2 acyl chain. For C (20):C(20:2⌬ 8,11 )PE, there is a segment of 7 consecutive methylene units in the sn-2 acyl chain located between the olefinic carbon of C(12) and the methyl terminus; this long linear segment extending from C(13) to C(19) is, by definition, the ATS. In the case of C(20):C(20: 3⌬ 8,11,14 )PE, a segment of 4 consecutive methylene units lies between C(15) and C (20) in the sn-2 acyl chain.…”

“…The length of this segment is 1 methylene unit shorter than that of the linear segment near the interface extending from C(3) to C(7). Consequently, the longer linear segment near the interface is designated as the ATS for C (20):C(20:3⌬ 8,11,14 )PE. This figure thus serves as an example to demonstrate that for certain series of lipids the ATS may switch its location along the sn-2 acyl chain as each additional ⌬-bond is progressively introduced into the sn-2 acyl chain of the lipid.…”

Dissociation of proton-bound complexes reveals geometry and arrangement of double bonds in unsaturated lipids

“…[1][2][3] However, determination of these critical features by mass spectrometry is challenging. Conventional low energy collision-induced dissociation (CID) is the mainstay of modern lipid analysis but for isomeric lipids CID mass spectra are often similar or identical; particularly where isomers differ only in double bond position and geometry (i.e., cis and trans isomers).…”