1‐O‐alkyl‐2‐(ω‐oxo)acyl‐sn‐glycerols from shark oil and human milk fat are potential precursors of PAF mimics and GHB

Abstract

This study examines the feasibility that peroxidation and lipolysis of 1-O-alkyl-2,3-diacyl-sn-glycerols (DAGE) found in shark liver oil and human milk fat constitutes a potential source of dietary precursors of platelet activating factor (PAF) mimics and of gamma-hydroxybutyrate (GHB). Purified DAGE were converted into 1-O-alkyl-2-acyl-sn-glycerols by pancreatic lipase, without isomerization, and transformed into 1-O-alkyl-2-oxoacyl-sn-glycerols by mild autooxidation. The various core aldehydes without derivatization, as well as the corresponding dinitrophenylhydrazones, were characterized by chromatographic retention time and diagnostic ions by online electrospray mass spectrometry. Core aldehydes of oxidized shark liver oil yielded 23 molecular species of 1-O-alkyl-sn-glycerols with short-chain sn-2 oxoacyl groups, ranging from 4 to 13 carbons, some unsaturated. Autooxidation of human milk fat yielded 1-O-octadecyl-2-(9-oxo)nonanoyl-sn-glycerol, as the major core aldehyde. Because diradylglycerols with short fatty chains are absorbed in the intestine and react with cytidine diphosphate-choline in the enterocytes, it is concluded that formation of such PAF mimics as 1-O-alkyl-2-(omega-oxo)acyl-sn-glycerophosphocholine from unsaturated dietary DAGE is a realistic possibility. Likewise, a C4 core alcohol produced by aldol-keto reduction of a C4 core aldehyde constitutes a dietary precursor of the neuromodulator and recreational drug GHB, which has not been previously pointed out.

Ether lipids

“…Low percentages of alkyl chains longer than 18 carbon atoms might indicate decreasing substrate tolerance of fatty acylCoA reductases toward fatty acids longer than 18 carbon atoms. Similar trends have been reported in the liver oil from Somniosus microcephalus, Chimaera monstrosa and deep-sea sharks (Hallgren and Larsson, 1962;Hartvigsen et al, 2006). In the teleost fish Siorella sp.…”

“…Indeed, FAR2 showed a strong specificity toward the saturated fatty acids of 16 and 18 carbon chains. Another interesting fact is that these two isoenzymes have different tissue distribution (Cheng and Russell, 2004;Hartvigsen et al, 2006). Therefore, the 1-O-alkyl composition appears to be determined primarily by fatty acyl-CoA reductases of different fatty acid selectivity.…”

“…Then, the DAGE fraction is separated from the total lipid extract by preparative thin layer chromatography (TLC) or column chromatography on silicic acid or silica gel (Hartvigsen et al, 2006;Kang et al, 1998;Malins et al, 1965;Sargent et al, 1973). After alkaline hydrolysis of the DAGE fraction the obtained 1-O-alkyl-sn-glycerols are derivatized to their corresponding isopropylidene (Kang et al, 1998;Malins et al, 1965), diacetylated (Sargent et al, 1973), disilylated (TMS) (Kang et al, 1998) or dimethoxylated (Hallgren and Larsson, 1962) derivatives prior to gas-liquid chromatography (GLC), equipped with flame ionization detector (FID) (Hallgren et al, 1974b;Hartvigsen et al, 2006;Kang et al, 1998), for analysis of the 1-O-alkyl chain profile. For further confirmation of the 1-O-alkyl-sn-glycerol peaks, GLC-mass spectrometry (GLC-MS) with an ion trap detector (ITD) has been applied (Kang et al, 1998).…”

A kinetic study of the lipase-catalyzed ethanolysis of two short-chain triradylglycerols: Alkylglycerols vs. triacylglycerols

“…In recent years, numerous synthetic ether lipids that do not occur in nature have been prepared to find therapeutic agents such as agonists and antagonists of natural lipid mediators [7]. One example of the mentioned synthetic ether lipids are PAF mimics that retain a short-chain residue esterified at the sn-2 position [8].…”

Lipidomic Analysis of Glycerolipid and Cholesteryl Ester Autooxidation Products

“…The protocols of these studies have been recently described [2]. (e) Hartvigsen et al [70] reported isolation of core aldehydes during peroxidation of alkylacylglycerols derived by lipolysis from alkyldiacylglycerols (DAGE) of shark oil and human milk fat. Detailed protocols of these transformations have been recently reported [2].…”