Dataset Information

Mass spectrometry-directed structure elucidation and total synthesis of ultra-long chain (O-acyl)-?-hydroxy fatty acids.

ABSTRACT: The (O-acyl)-?-hydroxy FAs (OAHFAs) comprise an unusual lipid subclass present in the skin, vernix caseosa, and meibomian gland secretions. Although they are structurally related to the general class of FA esters of hydroxy FAs (FAHFAs), the ultra-long chain (30-34 carbons) and the putative ?-substitution of the backbone hydroxy FA suggest that OAHFAs have unique biochemistry. Complete structural elucidation of OAHFAs has been challenging because of their low abundance within complex lipid matrices. Furthermore, because these compounds occur as a mixture of closely related isomers, insufficient spectroscopic data have been obtained to guide structure confirmation by total synthesis. Here, we describe the full molecular structure of ultra-long chain OAHFAs extracted from human meibum by exploiting the gas-phase purification of lipids through multi-stage MS and novel multidimensional ion activation methods. The analysis elucidated sites of unsaturation, the stereochemical configuration of carbon-carbon double bonds, and ester linkage regiochemistry. Such isomer-resolved MS guided the first total synthesis of an ultra-long chain OAHFA, which, in turn, confirmed the structure of the most abundant OAHFA found in human meibum, OAHFA 50:2. The availability of a synthetic OAHFA opens new territory for future investigations into the unique biophysical and biochemical properties of these lipids.

SUBMITTER: Hancock SE

PROVIDER: S-EPMC6071768 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

Mass spectrometry-directed structure elucidation and total synthesis of ultra-long chain (<i>O</i>-acyl)-ω-hydroxy fatty acids.

Hancock Sarah E SE Ailuri Ramesh R Marshall David L DL Brown Simon H J SHJ Saville Jennifer T JT Narreddula Venkateswara R VR Boase Nathan R NR Poad Berwyck L J BLJ Trevitt Adam J AJ Willcox Mark D P MDP Kelso Michael J MJ Mitchell Todd W TW Blanksby Stephen J SJ

Journal of lipid research 20180615 8

The (<i>O</i>-acyl)-ω-hydroxy FAs (OAHFAs) comprise an unusual lipid subclass present in the skin, vernix caseosa, and meibomian gland secretions. Although they are structurally related to the general class of FA esters of hydroxy FAs (FAHFAs), the ultra-long chain (30-34 carbons) and the putative ω-substitution of the backbone hydroxy FA suggest that OAHFAs have unique biochemistry. Complete structural elucidation of OAHFAs has been challenging because of their low abundance within complex lipi ...[more]

PMID: 29907595

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Project description:The skin is a flexible organ that forms a barrier between the environment and the body's interior; it is involved in the immune response, in protection and regulation, and is a dynamic environment in which skin lipids play an important role in maintaining homeostasis. The different layers of the skin differ in both the composition and amount of lipids. The epidermis displays the best characteristics in this respect. The main lipids in this layer are cholesterol, fatty acids (FAs) and ceramides. FAs can occur in free form and as components of complex molecules. The most poorly characterized FAs are very long-chain fatty acids (VLCFAs) and ultra long-chain fatty acids (ULCFAs). VLCFAs and ULCFAs are among the main components of ceramides and are part of the free fatty acid (FFA) fraction. They are most abundant in the brain, liver, kidneys, and skin. VLCFAs and ULCFAs are responsible for the rigidity and impermeability of membranes, forming the mechanically and chemically strong outer layer of cell membranes. Any changes in the composition and length of the carbon chains of FAs result in a change in their melting point and therefore a change in membrane permeability. One of the factors causing a decrease in the amount of VLCFAs and ULCFAs is an improper diet. Another much more important factor is mutations in the genes which code proteins involved in the metabolism of VLCFAs and ULCFAs-regarding their elongation, their attachment to ceramides and their transformation. These mutations have their clinical consequences in the form of inborn errors in metabolism and neurodegenerative disorders, among others. Some of them are accompanied by skin symptoms such as ichthyosis and ichthyosiform erythroderma. In the following review, the structure of the skin is briefly characterized and the most important lipid components of the skin are presented. The focus is also on providing an overview of selected proteins involved in the metabolism of VLCFAs and ULCFAs in the skin.

Dataset Information

Mass spectrometry-directed structure elucidation and total synthesis of ultra-long chain (O-acyl)-?-hydroxy fatty acids.

Publications

Mass spectrometry-directed structure elucidation and total synthesis of ultra-long chain (<i>O</i>-acyl)-ω-hydroxy fatty acids.

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