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Review
, 877 (26), 2814-21

Discovering Novel Brain Lipids by Liquid Chromatography/Tandem Mass Spectrometry

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Review

Discovering Novel Brain Lipids by Liquid Chromatography/Tandem Mass Spectrometry

Ziqiang Guan. J Chromatogr B Analyt Technol Biomed Life Sci.

Abstract

Discovery and structural elucidation of novel brain lipids hold great promise in revealing new lipid functions in the brain and in understanding the biochemical mechanisms underlying brain physiology and pathology. The revived interests in searching for novel brain lipids have been stimulated by the expanding knowledge of the roles of lipids in brain functions, lipids acting as signaling molecules, and the advent of lipidomics enabled by the advances in mass spectrometry (MS) and liquid chromatography (LC). The identification and characterization of two classes of novel lipids from the brain are reviewed here: N-acyl phosphatidylserine (N-acyl-PS) and dolichoic acid (Dol-CA). The identification of these lipids benefited from the use of efficient lipid fractionation and separation techniques and highly sensitive, high-resolution tandem MS.

Figures

Figure 1
Figure 1
Example structures of N-acyl phosphatidylserine (N-acyl-PS) and dolichoic acid (dol-CA).
Figure 2
Figure 2
Flow chart of procedures for the extraction, separation and MS characterization of brain lipids.
Figure 3
Figure 3
ESI-MS/MS identification and chemical structure of N-acyl-PS. (A) Negative ion ESI/MS of mouse brain lipids eluting from a DEAE-cellulose column in chloroform:methanol:120 mM aqueous ammonium acetate (2:3:1, v/v). (B) MS/MS of N-acyl-PS with [M-H]- at m/z 1026.78. (C) The proposed brain N-acyl-PS structure (1-stearoyl-2-oleoyl-sn-glycero-3-phospho-N-palmitoyl-serine) for the species with [M-H]- at m/z 1026.78. Abbreviations: PA, phosphatidic acid; CL, cardiolipin; PS, phosphatidylserine; ST, sulfatide.
Figure 4
Figure 4
A family of N-acyl-PS molecular species in mouse brain. (A) Expanded negative ion mass spectrum (m/z 980-1200) from Figure 1A, showing a family of N-acyl-PS [M - H]- ions. These N-acyl-PS species were identified by the exact mass measurements and MS/MS. (B) Complex N-acyl chain compositions, as revealed by MS/MS analysis of the peak at m/z 1074.77. The neutral losses in the MS/MS were used to identify the N-acyl chains: 373.25 amu for N-arachidonoyl-PS, 351.25 amu for N-oleoyl-PS, and 325.24 amu for N-palmitoyl-PS.
Figure 5
Figure 5
Proposed pathway for the biosynthesis of N-acyl-PS and its conversion to N-acyl serine. These reactions are analogous to those involved in the formation of N-acyl-PE and anandamide. Although PC is shown, other glycerophospholipids may serve as acyl donors. The predominance of the N-palmitoyl moiety in the N-acyl-PS series suggests that the N-acyl chain arises mainly from the sn-1 position of donor glycerophospholipids. PC, phosphatidylcholine; PS, phosphatidylserine; PA, phosphatidic acid.
Figure 6
Figure 6
Reverse phase LC/MS/MS identification of dol-CA from human neuromelanin (NM). (A) The total ion chromatogram of LC/MS (in the negative ion mode) of the lipid extract of NM isolated from the human SN. (B) Averaged mass spectrum (m/z 1180 - 1440) of the NM lipid species eluting from 15.5-17.0 min [shaded region in (A)]. The singly charged ions at m/z 1236, 1304, 1372, and 1440 are the acetate adduct [M + Ac] ions of dolichol species with chain lengths of n = 17, 18, 19, and 20, respectively. The starred peaks at m/z 1258, 1326, and 1394 are unknown species, later identified as the [M - H] ions of dol-CA species with n = 18, 19, and 20, respectively. (C) MS/MS spectrum and the proposed fragmentation scheme of the [M - H] ion at m/z 1258 for n = 18 dol-CA. (Figure adapted from Ref. [24])

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