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Lipid Matters - Archive of Older Blogs - 2019

This Blog is an occasional series of notes on publications or other items dealing with lipid science that seem to be of particular interest to the editor Bill Christie. Inevitably, the selection is highly personal and subjective. In this web page, the blogs for 2019 are archived, while those for other years can be accessed from the foot of the current blog page.

January 30th, 2019

Scottish thistleThere seems to be particular interest in the epoxyeicosatrienoic acids (EETs) at present because of their therapeutic potential, and a new study demonstrates that 11,12-EET enhances the process by which immature precursor cells develop into mature blood cells (hematopoiesis) and their further development (engraftment) in mice and zebrafish in vitro. For the first time, a receptor for EETs has been identified, i.e. GPR132 - a low-affinity EET receptor with physiological relevance in hematopoiesis (Lahvic, J.L. et al. Specific oxylipins enhance vertebrate hematopoiesis via the receptor GPR132. Proc. Natl. Acad. Sci. USA, 115, 9252-9257 (2018);  DOI).

The Journal of Biological Chemistry has just selected a paper that deals with EETs among other oxylipins as their paper of 2018 in their Lipids section (Moon, S.H. et al. Heart failure-induced activation of phospholipase iPLA2γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore. J. Biol. Chem., 293, 115-129 (2018);  DOI). In brief, in non-failing human hearts, one isoform of phospholipase A (cPLA2ζ) channels arachidonic acid into protective EETs, whereas in failing hearts, opening of the mitochondrial permeability transition pore increases the activity of a second isoform of phospholipase A (cPLA2γ) that channels arachidonic acid into toxic HETEs. A second lipid biochemistry paper is their 2018 choice for the Immunology section.

Incidentally, for those interested in the history of lipid science, my mentor and colleague Frank Gunstone was the first to identify and characterize a naturally occurring epoxy fatty acid, i.e. vernolic acid or 12,13-epoxy-octadec-cis-9-enoic acid from the seed oil of Vernonia anthelmintica (Gunstone, F.D. Fatty acids. Part II. The nature of the oxygenated acid present in Vernonia anthelmintica (Willd.) seed oil. J. Chem. Soc., 1611-1616 (1954);  DOI). He told me a few years ago that on thinking back, he was now especially pleased with this work because it was accomplished without the aid of chromatography, spectroscopic techniques or computers (any one remember tables of logarithms?). Rather, he had a balance, a burette and his knowledge of chemical reactions - see also his article in the Lipid Library for a general review of Fatty Acid Analysis before Chromatography. Frank recently celebrated his 96th birthday, but is frail and living in a retirement home. Happily, he has an extensive family nearby, including many greatgrandchildren, and he still has a zest for life.

January 23rd, 2019

In recent years, I have read any number of reviews extolling the virtues of the various methodologies available for lipidomics, especially in relation to mass spectrometry, but I have rather enjoyed reading one which deals more with the limitations. In addition to MS (with and without chromatography), nuclear magnetic resonance is discussed, as well as universal detectors for HPLC (evaporative light-scattering and charged-aerosol detectors) (Khoury, S. et al. Quantification of lipids: model, reality, and compromise. Biomolecules, 8, 174 (2018);  DOI - open access). With all of these, quantification is the main issue and the choice of internal standards is critical. While standards are available for most lipid classes, relatively few are available for specific molecular species. The authors point out that for example, 9856 species are listed in the LIPID MAPS® Lipidomics Gateway for glycerophospholipids but only about 80 analytical standards are available commercially. There may be differences in the response to species within a lipid class because of differences in fatty acid composition - hence the need for the 'compromise' of the title. Incidentally, I was pleased to see that there is still interest in universal detectors for HPLC, as I was under the impression that they were in danger of being forgotten.

While we should be aware of the limitations of mass spectrometry, we should also acknowledge its successes, and I have been impressed by a paper describing the separation and quantification of glucosyl- and galactosylceramides, which are virtually identical in structure, by differential ion mobility spectrometry (Xu, H.B. et al. DMS as an orthogonal separation to LC/ESI/MS/MS for quantifying isomeric cerebrosides in plasma and cerebrospinal fluid. J. Lipid Res., 60, 200-211 (2019);  DOI).

January 16th, 2019

A novel lipid to catch my eye this week is 1,28-octacosa-6,9,12,15-tetraenedioate or in other words a C28 dicarboxylic acid with four double bonds, probably produced in tissues by chain elongation of arachidonate, followed by ω-oxidation by various CYP450 enzymes (Wood, P.L. Endogenous anti-inflammatory very-long-chain dicarboxylic acids: potential chemopreventive lipids. Metabolites, 8, 76 (2018);  DOI). Although much about its origin is a matter for conjecture, plasma levels are greatly reduced in certain cancers, so it obviously warrants further investigation. It would also be interesting to know whether similar very-long-chain oxylipins remain to be discovered, as few analysts look that far out in chromatograms.

I am always intrigued by how natural selection has picked certain fatty acids for particular purposes. For example, myristic acid is a rather minor fatty acid in all tissues and it has no functional groups in the chain to modify its three-dimensional shape, yet it is used almost exclusively for N-acylation of proteins. Another fatty acid with perhaps surprising properties is palmitoleic acid (9-16:1), which unusually is O-acylated, as opposed to S- or N-acylated, to a specific serine residue in the Wtn family of proteins and is essential for their vital functions in fetal development (see my web page on proteolipids). Such fatty acylation of Wnt is also required for its recognition by the co-chaperone 'Wntless' and for its binding to the 'Frizzled' receptor family. For background, I had to look this up in Wikipedia and found that "When activated, Frizzled leads to activation of Dishevelled in the cytosol" - some biochemists obviously have a sense of humour, although it sounds like me getting up in the morning. A new review describes the structures of these proteins and how the palmitoleate fits into a specific groove in the receptor to facilitate binding and thence signalling (Nile, A.H. and Hannoush, R.N. Fatty acid recognition in the Frizzled receptor family. J. Biol. Chem., 294, 726-736 (2019);  DOI - Author's choice).

January 9th, 2019

Gangliosides are fascinating lipids, not least because they demolish any definition of lipids based on their solubility in organic solvents. In the Folch extraction procedure, gangliosides partition into the aqueous phase. There is no doubt that the bargain of the week is a comprehensive review (more than 300 references) of the chemistry and metabolism of gangliosides (Sandhoff, R. and Sandhoff, K. Emerging concepts of ganglioside metabolism. FEBS Letts, 592, 3835-3864 (2018);  DOI - open access). The article is dedicated to Professor Wilhelm Stoffel on the occasion of his 90th birthday. I have some work to do now to update my web page on this lipid class, especially as there is a further review article on glycosphingolipid-enriched lipid rafts in immune systems in the same journal issue (also open access).

ananatoside AThe first new lipid that I have encountered in the new year is an unusual glycolipid surfactant of bacterial origin (Gauthier, C. et al. Structural determination of ananatoside A: An unprecedented 15-membered macrodilactone-containing glycolipid from Pantoea ananatis. Carbohydrate Res., 471, 13-18 (2019);  DOI). It consists of glucose esterified to two 3-hydroxy fatty acids to form a novel cyclic structure.

For those fortunate enough to have access (not me), a new book is available - "Sphingolipids in Cancer" edited by Charles E. Chalfant and Paul B. Fisher (Advances in Cancer Research, Volume 140, Pages 1-388 (2018)), while a substantial review on lipid rafts has been published (Cebecauer, M. et al. Membrane lipid nanodomains. Chem. Rev., 118, 11259-11297 (2018);  DOI).

Why do PDF files from journals vary so much in size? A 9-page pdf that I downloaded from one journal this week was 16Mb, while a 30-page pdf in another was only 2 Mb; the number and quality of the illustrations did not seem to be a factor. I have a fast broadband connection and more disk space than I am every likely to need, so it hardly matters to me, but what about our scientific colleagues around the world without such generous provision?

I am not sure if the word 'fatberg' has found its way into any modern dictionary, but their existence is certainly proving a concern to towns in the UK (see the BBC News website). This is one problem in lipid science/technology that I am happy to leave to others to solve.

January 2nd, 2019

At this time of year, I have usually looked back through the reference lists in my literature survey pages to see which lipid classes have been trending in relation to my Lipid Essentials pages. This approach is not ideal in that a single review issue of a journal can distort the picture, but every year until now, sphingosine-1-phosphate and phosphoinositides have topped the list. Instead, this year I have used the log that I keep of the regular updates to my web pages in this section to determine where I have had to make most improvements. These can range from simply a new reference and/or a line of text to more substantial revisions (and hopefully on rare occasions only to correction of errors). The clear winner under my new approach was my web page on hydroxyeicosatetraenoic acids (HETE) closely followed by that on specialized pro-resolving mediators (SPMs). If the web page on leukotrienes is also taken into account, it is evident that oxylipin research is where I appear to be noticing appreciable progress. Among the glycerolipids, triacylglycerols (surprisingly?) and phosphoinositides tied for first place (although the latter wins when the web page on glycosylphosphatidylinositol anchors for proteins is taken into account), with the web page on phosphatidic acid (and lysoPA) a close third. Endocannabinoids were also well represented in my updates. Other than sphingosine-1-phosphate, my sphingolipid web pages tended to be updated relatively less frequently, as were those on fatty acids other than oxylipins. The poor relations were the web pages on cyanolipids (zero updates), and ceramide-1-phosphate and hopanoids (1 each).

The first special review issue of a journal of the new year is on the topic of "Brown and Beige Fat: From Molecules to Physiology" edited by Paul Cohen (Biochim. Biophys Acta, 1864, Issue 1, Pages 1-112 (January 2019)).

Blogs for the previous year (2018) can be located here..

Author: William W. Christie Updated: June 5th, 2019 Credits/disclaimer LipidWeb logo