The LipidWeb blank

Lipid Matters - Archive of Older Blogs

This Blog, 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, is archived for about a year here before deletion. Inevitably, the selection is highly personal and subjective. The current blog (and the previous few months) can be accessed here..

July 26th, 2017

Scottish thistleFollowing on from last week's blog, a paper on protein S-palmitoylation has caught my attention. New methodology involving a site-specific acyl-biotin-exchange reaction for the complete palmitoylated-proteome of a tissue has enabled the identification of what appears to me at least to be an extraordinary number of palmitoylation sites in brain tissue (Collins, M.O. et al. Global, site-specific analysis of neuronal protein S-acylation. Sci. Rep., 7, 4683 (2017);  DOI). 490 Palmitoylation sites have been identified on 342 synaptic proteins, 44% of which are integral membrane proteins. It is now apparent that protein palmitoylation is essential for intracellular signalling and for the folding, trafficking and function of such disparate proteins as Src-family kinases, Ras family GTPases, G-proteins and G-protein coupled receptors. Many of the palmitoylation sites co-located with phosphorylation sites, and it seems to me that the biochemical world must now regard protein palmitoylation-depalmitoylation in the same light as phosphorylation-dephosphorylation in the regulation of enzyme activity.

My enthusiasm for the potential of bacterial lipopeptides as a source of new antibiotics (see last week also) has taken something of a blow with a new publication describing the practical difficulties in recovering them from natural sources (Coutte, F. et al. Microbial lipopeptide production and purification bioprocesses, current progress and future challenges. Biotechn. J., 12, 1600566 (2017);  DOI). There are three major challenges: bacteria produce quorum-sensing molecules that sense cell density and thence limit their growth - the more important of these are in fact lipids, i.e. N-acylhomoserine lactones. Secondly there are problems of foam production because of the amphiphilic nature of the products that cause handling difficulties, and finally the complex mixtures formed are not easily resolved into single components. It may take time but I suspect these problems will eventually be overcome.

Both publications cited this week are open access. Incidentally, I maintain a rough log of my updates to my Lipid essentials pages here. Last year sphingosine 1-phosphate and phosphoinositides received most attention, this year so far it is proteolipids and isoprostanes.

July 19th, 2017

In the search for new antibiotics, lipopeptides appear to offer great potential if problems of toxicity can be overcome. Paenibacillus sp. have proved to be of special interest, and a new report describes a fresh isolate that produces novel cyclic and linear lipopeptides, both of which have antibiotic activity against Gram-negative and Gram-positive bacteria (Huang, E. et al. New Paenibacillus strain produces a family of linear and cyclic antimicrobial lipopeptides: cyclization is not essential for their antimicrobial activity. FEMS Microbiol. Letts, 364, fnx049 (2017);  DOI). Much of the emphasis of recent work has been on cyclic lipopeptides, but chemical synthesis of linear lipopeptides is much easier technically than of cyclic equivalents so this should open up opportunities for the design and testing of new families of related molecules for their therapeutic value.

When I was revising my web page on protein acylation (proteolipids) recently, I became aware that I had written much less on N-myristoylation than on S-palmitoylation, and this was reflected in the reading list at the end. On thinking it over, I believe this is because the latter is a more dynamic modification, the regulation of which can be seen to be relevant to a host of metabolic processes. Indeed, one element of the regulation of the activity of N-myristoylated proteins is additional S-palmitoylation/deacylation reactions. I was able to redress the balance a little after reading a new open access publication (Udenwobele, D.I. et al. Myristoylation: an important protein modification in the immune response. Front. Immunol., 8, 751 (2017);  DOI). Incidentally, a second open access review in this general area was published this week (Chen, J.J. and Boehning, D. Protein lipidation as a regulator of apoptotic calcium release: relevance to cancer. Front. Oncol., 7, 138 (2017);   DOI).

July 12th, 2017

It is astonishing how the view of lipids held by biochemists has changed in the last 50 years. I have to confess that I did not always recognize each milestone in lipid science as it was achieved but I can look back now in admiration of the work of so many of my contemporaries. One such is William Dowhan who has just described his career and research philosophy in an open access publication (Dowhan, W. Understanding phospholipid function: Why are there so many lipids? J. Biol. Chem., 292, 10755-10766 (2017);  DOI). While signalling was a major focus for research in the lipid field over the period, Dowhan was instead pioneering the study of how lipids interact with proteins to modify their functions using E. coli as his model organism to reveal "direct lipid-protein interactions that govern dynamic structural and functional properties of membrane proteins". I can recommend this as a good read both for the science and as a personal record of a distinguished career. Incidentally, he published a review with a very similar title back in 1997, and it is fascinating to learn what has been accomplished since then.

I was not around when cholesterol was discovered and a new open access review marks the 200th anniversary of the recognition by the great French chemist Michel Chevreul that it was a non-saponifiable lipid present in gall stones (Chaudhuri, A. and Anand, D. Cholesterol: Revisiting its fluorescent journey on 200th anniversary of Chevruel's "cholesterine". Biomed. Spectr. Imaging, 6, 1-24 (2017);  DOI). Aside from the fascinating historical introduction (in which the subject's name is unfortunately misspelt), this open access publication describes the use of fluorescent probes in studying cholesterol function in cells. My former mentor Frank Gunstone kept a picture in his office of Chevreul at work in his laboratory in his 100th year, and I reproduce it below. Now there is an ambition!

Chevreul in laboratory

If I am to achieve this, it seems that I have to keep up my fish and presumably fish oil consumption (Zeng, L.F. et al. An exploration of the role of a fish-oriented diet in cognitive decline: a systematic review of the literature. Oncotarget, 8, 39877-39895 (2017);  DOI).

July 5th, 2017

Eric Murphy makes a cogent plea for respect for copyright in an editorial in the latest issue of Lipids (Murphy, E.J. An ethical dilemma: to share or not to share your paper published in Lipids using an on-line outlet. Lipids, 52, 573-574 (2017);  DOI). Posting papers to sites such as ResearchGate is a breach of copyright if the paper is not already open access and is undoubtedly illegal. He suggests that rather than doing this authors should use open access journals if they feel strongly about freedom of use. While I am sympathetic to much of what he says, I do not believe that the problem can be discussed entirely in such black and white terms. If I email an author and ask for a pdf file of a paper in the same way as years ago I might have requested a reprint, this probably comes into the category of fair use, but if we extend this to consider a correspondent who sends me a pdf file of a paper not his own to which I do not have immediate access, should I have to search my conscience? Who am I cheating; there is no way that as a private retiree I could consider spending up to £40 as demanded by publishers for a pdf file that may or may not be of use to me (though if it were £2 I might). If I accept an 'illegal' copy, I will not distribute it elsewhere and I will cite it in this website so the authors and the journal get some publicity at least.

Ethics aside, it is hard to feel sorry for scientific publishers, some of whom are apparently making huge profits on turnover according to an article in the Guardian newspaper. For example in 2010, Elsevier made a 36% profit on turnover. When you consider that they do not have to pay anything to authors or referees this seems grossly excessive. On the other hand, I have no sympathy for sites such as Sci-Hub, who according to Nature News have just been ordered by a US court to pay US$15 million in damages to Elsevier for copyright infringement, although the latter are unlikely to see any of this money as the site is run out of the jurisdiction of the court in Russia. As I understand it, this site is still operating and largely offering preprints of papers without charge, although they are aggressive in seeking donations (assuming that anyone is willing to send bank/credit card details to Russia). Incidentally, the problem is not new in that I recently read a biography of Charles Dickens, who was greatly aggrieved because US publishers reprinted his books as soon as they could get their hands on them without paying him royalties.

What is the answer? Apart from having more open access journals and papers, I would be content if more publishers allowed access to back content after 1-2 years as is already the case with many non-commercial journals especially those with a biological remit. It seems wrong that I am not able to have digital copies of my own papers in journals published by the Royal Society of Chemistry in the 1960s without paying a hefty fee.

June 28th, 2017

Scottish thistleThe journal Biochim. Biophys. Acta - Molecular and Cell Biology of Lipids has a special Issue for August just online entitled "BBALIP_Lipidomics Opinion Articles" and edited by Sepp Kohlwein. At first glance, there seems to be a wide and diverse range of topics going beyond the technical aspects into the biology. While I am fascinated and a little envious of the new methodology, I am more interested in the results. So far, I have only had time to look at one of the reviews, which is highly relevant to my Lipid Essentials pages here in relation to presentation of data (Liebisch, G. et al. Reporting of lipidomics data should be standardized. Biochim. Biophys. Acta, 1862, 747-751 (2017);   DOI). Many of the points made seem sensible, including the suggestion that data should be reported in terms of absolute amounts although I am not clear whether they mean by weight or in terms of molar amounts. They also suggest that data should be available in spreadsheets rather than Word documents or pdf files to make inter-laboratory comparisons easier.

In my articles here, I do not quote any analytical data made by modern mass spectrometric methods - all come from papers published in the 70s and 80s when the methodology was more time consuming but capable of high precision. The problem is that data obtained now in terms of molecular species compositions are in a format that does not lend itself to simple presentation. A phospholipid with 10 fatty acids can exist in the form of 90 molecular species, including positional isomers on the glycerol moiety, while a similar triacylglycerol can have 500 species not including enantiomers. When I came into lipid science, we were more concerned with positional distributions of fatty acids as determined following hydrolytic cleavage with specific lipases; analysis of molecular species was often secondary. It was a simple task to tabulate data for the fatty acid composition of each position in a phospholipid as two columns of fatty acids normalized to 100 mol% with roughly 10 numbers in each. Comparison of data from other laboratories was straight forward, and if you need examples look at almost any of the tables in my web page here on triacylglycerol compositions where data from several sources are presented in a single table.

Such positional data are relevant to biosynthetic processes, hydrolysis by enzymes and lipid remodelling. To give just two examples, arachidonic acid from position sn-2 of phospholipids is used for eicosanoid production while that from position sn-1 is used for anandamide biosynthesis. Of course, molecular species data are important also but this may not be as immediately obvious.

Although mass spectrometric methodology produces data in the form of amounts of the various molecular species, is it necessarily to present it in this form only? Lipidomics methodology is available to determine positional distributions of fatty acids on the glycerol moiety in each species, and while I am not up to date on the mechanics of this there are certainly plenty of papers on the topic. I suspect that the older methods may be capable of greater precision, but mass spectrometry may be good enough for comparative purposes. If so, would it not be possible to add simple mathematical formulae to the spreadsheets to generate tables of positional data for the fatty acids in each lipid class from the molecular species data? Data in both formats are important, but a simple comparison of positional data for each lipid as a first step in interpretation might point to the areas of the molecular species information that require a closer examination. It would certainly simplify interlaboratory comparisons.

June 21st, 2017

In this blog, I have often discussed the therapeutic potential of particular lipids against human diseases. It may be worth a reminder that lipids can have similar beneficial functions in plants. For example, plants in the Solanacea and other families have glandular trichomes, i.e. secretory organs on the external surfaces that secrete mixtures of sugar esters onto the plant aerial surfaces that act as protective agents against both insect herbivores and pathogenic fungi Luu, V.T. et al. O-Acyl sugars protect a wild tobacco from both native fungal pathogens and a specialist herbivore. Plant Physiol., 174, 370-386 (2017);  DOI). In the tomato, for example, these metabolites consist of a carbohydrate backbone, usually glucose or sucrose, to which two to five fatty acids are esterified. The aliphatic acyl chains vary in length from C2 to C12 and are straight chain or have iso- or anteiso-methyl-branches.

My open access publication of the week is perhaps more mainstream and deals with the role of sphingolipids in brain development (Olsen, A.S.B. and Færgeman, N.J. Sphingolipids: membrane microdomains in brain development, function and neurological diseases. Open Biol., 7, 170069 (2017);  DOI).

In the discussion of the new biologically active lipids 'FAHFA' (Fatty Acid Hydroxy Fatty Acid), I do not recall the term "estolide" mentioned although this has been in use since at least the 1950s (according to Google scholar). The definition from the review cited here is "they are intermolecular esters comprised of at least two fatty acid molecules". In animals, the best known example is skin ceramides, but they are also present in bacteria (ornithine lipids and lipid A), many seed oils and yeast. However, the FAHFA are distinctive and differ from the rest in that they have a free carboxyl group. As an example, it may seem something of a misnomer, but hexaacyl triacylglycerols were reported from ergot oil, i.e. with three moles of ricinoleate attached to glycerol each of which is esterified with a long chain fatty acid (Morris, L.J. and Hall, S.W. Structure of glycerides of ergot oils. Lipids, 1, 188-196 (1966);  DOI). In fact, estolides are important industrial products with applications in lubricants (Zerkowski, J.A. Estolides: From structure and function to structured and functionalized. Lipid Technology, 20, 253-256 (2008);  DOI). Incidentally, this review suggests that the first description of an estolide may have been "a 1915 report in Die Naturwissenschaften mentioning their isolation from conifer needles".

I was not around in 1915, but I do remember Lindsay Morris - the author of the 1966 paper. He was a few years ahead of me first as a PhD student with Frank Gunstone and then as a post doc with Ralph Holman, so I knew him first simply as a legendary figure for his activities both within and out of the lab. He will be best remembered as one of the inventors of silver ion chromatography. When we did eventually meet, I found him an engaging person with boundless energy and enthusiasm. I understand that he moved back to Scotland when he retired from Unilever Research, and sadly he died a few years ago.

June 14th, 2017

In my essays here, I have used a rather strict definition of what constitutes an endocannabinoid, i.e. that they must interact with the cannabinoid receptors CB1 and CB2. Thus of the amides, anandamide is obviously an endocannabinoid as is oleamide, but oleoylethanolamide is not. For many purposes this is a useful practical distinction, but there are grey areas and I wonder if I have been too pedantic especially as the 'true' endocannabinoids interact with a number of other receptors. Perhaps we need a new collective term that embraces all the fatty acid amides and simple lipaminoacids - 'amidolipins'? For example, of the other amides palmitoylethanolamide does not interact with the CB1 and CB2 receptors to a significant extent, but it has does have synergistic or "entourage" effects with the 'true' endocannabinoids. This interesting lipid exerts many biological effects in its own right, apparently by a multiplicity of mechanisms and receptors that impinge upon the activities of the other acyl amides. It is undergoing clinical trials for the relief of chronic pain and is the subject of a new review (Petrosino, S. and Di Marzo, V. The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. Brit. J. Pharmacol., 174, 1349-1365 (2017);   DOI).

The N-acylserotonins are another class of fatty amides that also fall into a grey classification area, simply because we do not yet appear to know with which receptors they interact. In particular, it is now clear that N-docosahexaenoylserotonin is present in human intestinal tissue and is a potent anti-inflammatory mediator that may be relevant to intestinal inflammatory conditions such as Crohn's disease and ulcerative colitis. It is a fascinating addition to the list of lipids containing polyunsaturated fatty acids of the (n-3) family with beneficial properties (Wang, Y. et al. Docosahexaenoyl serotonin emerges as most potent inhibitor of IL-17 and CCL-20 released by blood mononuclear cells from a series of N-acyl serotonins identified in human intestinal tissue. Biochim. Biophys. Acta, 1862, 823-831 (2017);   DOI).

In relation to the 'true' endocannabinoids, a new review suggests that some of their biological properties may be mediated through the production of nitric oxide, which functions as a versatile signalling intermediate and is ubiquitous in tissues (Lipina, C. and Hundal, H.S. The endocannabinoid system: ‘NO’ longer anonymous in the control of nitrergic signalling? J. Mol. Cell Biol. 9, 91-103 (2017);   DOI).

June 7th, 2017

The presence of α-galactosylceramide as opposed to the β-form in human tissues and its astonishing biological activity as an anti-tumor immunotherapeutic agent has been one of the pleasant surprises of this year (and has featured earlier this year in this blog). Indeed, I understand that it is undergoing clinical trials as an anti-tumor agent. One major difficulty in studying its metabolism and function is the low levels at which it occurs naturally in tissues (0.02% of the total galactosylceramides in RBL-CD1d cells, for example). A new LC-MS2 separation of the stereoisomers has now been described that appears to solve the problem (von Gerichten, J. et al. Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals. J. Lipid Res., 58, 1247-1258 (2017); DOI). As this lipid is produced by intestinal bacteria, it is a useful reminder after my previous two blogs that bacteria have many virtues and they are not always harmful. It is a truism that advances in methodology often lead to advances in the science, so watch this space. If I want to be picky, I would raise my old chestnut that the term "hydrophilic interaction chromatography" applied to the separation is meaningless unless we know more about the nature of the stationary phase. In fairness to authors, the manufacturers are often silent on this point.

The Journal of Steroid Biochemistry and Molecular Biology has published a special issue on the topic of "Oxysterols: Players in Different Metabolic Leagues" (Volume 169, Pages 1-234 (May 2017)) and edited by Luigi Iuliano, Dieter Lütjohann, Gérard Lizard and Ingemar Bjorkhem.

May 31st, 2017

Scottish thistleWe can never fully free ourselves of the national and occupational stereotypes that are part of our cultural heritage, and I am sure my readers will have an idea at the back of their mind of a "typical" Scotsman. Our view of Russians and scientists is of a very serious and possibly humorless people, so it was a rather pleasant surprise to find an item in Nature NewsDOI ) regarding a 'Monument to an Anonymous Peer Reviewer' outside the Higher School of Economics in Moscow. Immortalized in concrete, "the sculpture takes the form of a die displaying on its five visible sides the possible results of review - 'Accept', 'Minor Changes', 'Major Changes', 'Revise and Resubmit' and 'Reject'." One more stereotype bites the dust.

Phosphatidylserine is known to have an important role in the regulation of apoptosis or programmed cell death, the natural process by which aged or damaged cells are removed from tissues before they can exert harmful effects. A new review (open access) gives a clear explanation of the process in relation to erythrocytes, where phosphatidylserine is located in the inner leaflet of the membrane bilayer under low Ca2+ conditions when a phospholipid scramblase is suppressed by membrane cholesterol, but it is exposed to the outer leaflet under elevated Ca2+ concentrations which activate the scramblase (Arashiki, N. and Takakuwa, Y. Maintenance and regulation of asymmetric phospholipid distribution in human erythrocyte membranes: implications for erythrocyte functions. Curr. Opinion Hemat., 24, 167-172 (2017); DOI). The phosphatidylserine on the outer leaflet of the cell is then recognized by a receptor on the surface of macrophages and related scavenger cells, and these proceed to remove the apoptotic cells in a non-inflammatory manner.

Last week, I discussed two reviews that dealt with the sneaky ways pathogens made use of the lipids of their hosts for their own nefarious purposes. A new review that has the virtue of being open access discusses this in relation to cholesterol specifically (Samanta, D. et al. Manipulation of host cholesterol by obligate intracellular bacteria. Front. Cell. Inf. Microbiol., 7, 165 (2017); DOI). To gain entry into cells, pathogens utilize the cholesterol-rich microdomains in membranes known as rafts. Then, it is apparent that they can manipulate host cholesterol metabolism, including uptake, efflux, and storage, to access nutrient-rich vesicles or acquire membrane components. They also hijack the host cell signaling pathways involving cholesterol that are favorable for their intracellular survival.

The Journal of Experimental Botany has a special issue devoted to the "The Flowering of Jasmonate Research" (1 March, 2017).

May 24th, 2017

A week in the Canary Islands has taken my mind off lipid science for a time, but now I have twice as many papers as usual to read. A catchy title to a review often heralds a more entertaining discussion to follow as in this instance (Pathak, D. and Mallik, R. Lipid - motor interactions: soap opera or symphony? Curr. Opinion Cell Biol., 44, 79-85 (2017); DOI). Motor proteins are here defined as "ATPases that convert chemical energy into mechanical energy to drive many cellular functions including intracellular transport of vesicles". These enzymes require interactions with specific lipids, especially the phosphoinositides and cholesterol, to direct them to specific membranes. As to "soap opera etc", read the first paragraph for an elegant explanation of the analogy. The protein can have highly specific binding sites for particular lipids or it can indirectly react to membrane curvature induced by characteristic lipid head groups. Here much of the discussion focuses on the endosome/phagosome compartment partly because of the importance to normal cellular metabolism, and partly because pathogens in phagosomes use the lipid interactions to survive in host cells. Incidentally, there is a rather substantial new (if relatively inaccessible) book chapter that relates to the latter process (Fozo, E.M. and Rucks, E.A. The making and taking of lipids: the role of bacterial lipid synthesis and the harnessing of host lipids in bacterial pathogenesis. Adv. Microb. Physiol., 69, 51-155 (2016); DOI).

I am a spectator only to modern mass spectrometric techniques, but I have the impression that advances in software and data management are as important as those in instrumentation in driving what can now be achieved. For example, LipidFinder optimizes analysis based on users' own data, and a new open access publication describes its use to identify three 12-hydroxyeicosatetraenoic acid phosphoinositides in thrombin-activated platelets (O'Connor, A. et al. LipidFinder: A computational workflow for discovery of lipids identifies eicosanoid-phosphoinositides in platelets. JCI Insight, 2, e91634 (2017); DOI). Another research group describes the use of the software IE-Omics to automate data acquisition by MS/MS in sequential injections to improve the coverage of the lipidome especially with regard to trace species (Koelmel, J.P. et al. Expanding lipidome coverage using LC-MS/MS data-dependent acquisition with automated exclusion list generation. J. Am. Soc. Mass Spectrom., 28, 908-917 (2017); DOI).

The therapeutic potential of docosanoids such as the resolvins is increasingly becoming evident, and an application of 17(R)-hydroxy-docosahexaenoic acid to the relief of pain in osteoarthritis, if not yet the underlying cause, in animal models is described in a new publication hopefully as a prelude to clinical studies (Huang, J.T. et al. Targeting the D series resolvin receptor system for the treatment of osteoarthritis pain. Arthritis Rheumatol., 69, 996-1008 (2017); DOI).

May 10th, 2017

There is a short series of reviews on the theme of 'Lipid Methodology' (edited by Howard Goldfine and Ziqiang Guan) in a recent issue of Analytical Biochemistry (Volume 524, Pages 1-76 (1 May 2017)). One of these dealing with cholesterolomics is open access, but the one that caught my eye especially deals with the various modes of high-performance liquid chromatography that can be applied for the separation of regio- and stereoisomers of triacylglycerols (Rezanka et al. Regioisomeric and enantiomeric analysis of triacylglycerols. Anal. Biochem., 524, 3-12 (2017); DOI). Modern mass spectrometric methods dominate the recent analytical literature, but they cannot accomplish stereospecific analysis of triacyl-sn-glycerols, so I am always encouraged to see that alternative methods are still being pursued.

Some months ago, my attention was drawn to the fact that some subjects were being reviewed to exhaustion, with more than 20 reviews a year devoted to each of the topics of phosphoinositides and sphingosine-1-phosphate in particular. Of course, the reason these topics receive so much attention is because they are so dynamic and there is much important new research to discuss. Therefore, I make no apology for drawing your attention to a new review dealing with sphingosine-1-phosphate, which among its many virtues is open access (Pyne, N.J. and Pyne, S. Sphingosine 1-phosphate receptor 1 signaling in mammalian cells. Molecules, 22, 344 (2017); (2017); DOI).

May 3rd, 2017

One of the more surprising lipid discoveries in recent years has been fatty acids with a centrally located hydroxyl group to which a further fatty acid is linked as an estolide or 'FAHFA' (Fatty Acid Hydroxy Fatty Acid), such as the palmitoyl ester of 9-hydroxy-stearic acid (note that both component fatty acids are fully saturated), which was first found in the adipose tissue of mice. These have anti-diabetic and anti-inflammatory effects, even when administered orally, and they protect against colitis by regulating gut innate and adaptive immune responses. Although details of the biosynthesis have still to be established, there seems little doubt that they are formed endogenously as a new study has established that the hydroxyl group has defined stereochemistry, i.e. it is of the R-configuration (Nelson, A.T. et al. Stereochemistry of endogenous palmitic acid ester of 9-hydroxystearic acid and relevance of absolute configuration to regulation. J. Am. Chem. Soc., 139, 4943-4947 (2017);   DOI). Unfortunately, I am dependent on the abstract for this information as access is closed to non-subscribers.

I try to keep up with with the plethora of new eicosanoids and docosanoids that continue to be discovered, but I did not realize that more than 70 oxygenated metabolites of docosahexaenoic acid (DHA) had been discovered to date as summarized in a new review (Kuda, O. Bioactive metabolites of docosahexaenoic acid. Biochimie, 136, 12-20 (2017);  DOI). Included among these are FAHFA derived from essential fatty acids, i.e. with 14-hydroxydocosahexaenoic acid (14-OH-DHA) esterified to 9- and 13-hydroxyoctadecadienoic acids, for example; these have profound anti-inflammatory effects.

A few weeks ago, I pointed out here that the Journal of Lipid Research had taken a retrograde step in closing access to papers that had been accepted but were still in manuscript form. Either this was a technical error or they have seen the error of their ways and this policy has now been reversed.

April 26th, 2017

Scottish thistleUrine samples are usually regarded as the easiest non-invasive method of obtaining samples for analysis, but then any metabolites have passed through the kidney and may have been substantially altered. I had not considered human tears for this purpose, but it seems that tear fluid can serve as a means to identify and monitor novel biomarkers in ocular and systemic disease, and in particular the specialized pro-resolving mediators (SPMs). For example, resolvin D1, protectin D1, lipoxin A4, and resolvin E1 are accessible in this way in quantities that are known to be active biologically (English, J.T. et al. Identification and profiling of specialized pro-resolving mediators in human tears by lipid mediator metabolomics. PLEFA, 117, 17-27 (2017);   DOI). When I first saw the title, it brought to mind the old Julie London song "Cry me a River", but it seems that only 100μl of tears obtained "through an induction of an emotional response" were required for the identification and quantification of 21 different metabolites. This seems an astonishing example of the sensitivity of modern mass spectrometric methodology. The results are also surprising in that while SPMs were detected in male donors, they were essentially absent in females. Incidentally, if any of my younger readers don't know the above song (or the Barbra Streisand version), a treat awaits you.

Another record appears to have been broken in that trace levels of highly unsaturated fatty acids of the (n-3) family suggested to be 38:7(n-3) to 44:12(n-3) have been reported from brains of patients with genetic impairments of peroxisome function. The last must be the most highly unsaturated fatty acid of conventional origin known (Takashima, S. et al. Detection of unusual very-long-chain fatty acid and ether lipid derivatives in the fibroblasts and plasma of patients with peroxisomal diseases using liquid chromatography-mass spectrometry. Mol. Gen. Metab., 120, 255-268 (2017);  DOI).

April 19th, 2017

Some years ago, I took issue with the LipidMaps consortium over some aspects of their lipid classification system. In particular, I though they were wrong to create a distinct class for glycerophospholipids while lumping glycosyldiacylglycerols in with triacylglycerols. As glycosyldiacylglycerols can substitute for phospholipids under conditions of phosphate deprivation in plants and both function exclusively in membranes, I believed that both groups should have the same ranking. Apparently, I did not persuade them as the ranking did not change. One lipid that is particularly anomalous in this classification is the highly polar plant sulfolipid sulfoquinovosyldiacylglycerol, which cannot be compared with storage lipids in any respect; it is the subject of a new review (Goddard-Borger, E.D. and Williams, S.J. Sulfoquinovose in the biosphere: occurrence, metabolism and functions. Biochem. J., 474, 827-849 (2017);   DOI). As access is closed to non-subscribers, I am grateful to a friend for giving me a sight of it. While I was familiar with much of what the authors had to say about the biochemistry and function, I was not aware that it was such an important component of the sulfur cycle in the biosphere. The total annual synthesis of sulfolipid is thought to be of the order of 1013 kg per annum!

The March issue of Biochimie (Volume 134, Pages 1-138 (March 2017)) contains a number of articles with the theme of brown fat metabolism (Edited by Frédéric Bouillaud, Louis Casteilla, Susanne Klaus and Bruno Miroux). The May issue of this journal (Volume 136, pages 1-104) is devoted to "Pleiotropic physiological roles of PPARs and fatty acids: A tribute to Paul Grimaldi" (edited by Nada A. Abumrad, Ez-Zoubir Amri, Serge Luquet and Claude Forest).

Fatty acid binding proteins (FABPs) are a family of small cytoplasmic proteins that are highly conserved and as the name suggests bind long-chain fatty acids; they facilitate the transfer of fatty acids between extra- and intracellular membranes and receptors. Of these, FABP7 is located in astrocytes of the brain and binds DHA with the highest affinity. It is now reported to be required for normal sleep in humans and other animals. There is a brief popular report in Sci News with a link to the original article.

I have come across the Latin expression "in silico" in the titles of several recent publications, and I now understand that this means "in silicon" strictly speaking but is used to mean "performed on computers or via computer simulation". Those ancient Romans were cleverer than I would have believed if they knew of silicon and anticipated the use of computers.

April 12th, 2017

An item in Nature News drew my attention to Unpaywall - a free web-browser extension that hunts for papers in more than 5,300 repositories worldwide, including preprint servers and institutional databases, to find freely accessible (and legal) copies of research articles. It is an add-on to Firefox or Google Chrome that is quick and easy to install and use. In a brief trial, it found me one paper quickly that I needed to update these pages, and just as importantly found that two of interest were not available yet as open access so saving time in fruitless searching. The article in Nature suggests that more such tools are on the way.

The titles of some publication simply shout for attention (e.g. Li, X.B. et al. The slim, the fat, and the obese: guess who lives the longest? Current Genetics, 63, 43-49 (2017);   DOI). It appears that there is a phenomenon called the "obesity paradox" in that the overweight population enjoys the lowest rate of mortality from all causes in contradiction to everything that scientists and clinicians think they know. The authors believe that the answer may lie in a new cytoprotective function of triacylglycerols. As a relatively lean 140 pounder, should I be worried? Certainly, I wont feel guilty next time I am offered a big sugary doughnut with my morning coffee.

Fascinating new lipids are discovered all the time, but occasionally nature springs a nasty surprise. The latest in this category are alkyl cyanides produced by bacterial species. These can be either unbranched saturated or unsaturated with an omega-7 double bond, such as (Z)-11-octadecenenitrile, or methyl-branched unsaturated cyanides with the double bond located at C-3, such as (Z)-13-methyltetradec-3-enenitrile. Fatty acids are the biosynthetic precursors, and these are first converted into their amides and then dehydrated. While their functions are not yet known, some of these nitriles showed bactericidal activity; any possible homicidal properties were not investigated (Vidal, D.M. et al. Long-chain alkyl cyanides: unprecedented volatile compounds released by Pseudomonas and Micromonospora bacteria. Angew. Chem.-Int. Ed., 56, 4342-4346 (2017);   DOI). Some plant species contain cyanolipids but of a very different kind.

Formula for an alkyl cyanide

April 5th, 2017

I have commented on the uniqueness of cardiolipin in this blog on many occasions in the past, usually in relation to its special functions in membranes. Perhaps the most distinctive feature is that it possesses a dimeric structure in essence with four acyl groups arranged in a very limited range of molecular species. In heart muscle, for example, linoleate makes up 80% of the total fatty acids, so a high proportion of the lipid exists as the tetralinoleoyl species. This composition is attained after its initial synthesis by a remodelling process, catalysed by the enzyme tafazzin, which transfers fatty acids from other phospholipids by a mechanism that does not require a coenzyme A ester as an intermediate, and it is reversible. The question has arisen as to whether the fatty acid specificity is inherent in tafazzin per se or is dependent on thermodynamic considerations. It now appears that the question has been answered definitively by two papers from the laboratory of Professor Michael Schlame (Schlame, M. and Greenberg, M.L. Biosynthesis, remodeling and turnover of mitochondrial cardiolipin. Biochim. Biophys. Acta, 1862, 3-7 (2017);   DOI; Schlame, M. et al. The basis for acyl specificity in the tafazzin reaction. J. Biol. Chem., 292, 5499-5506 (2017);   DOI). It seems now to be established that sufficient energy differences arise from the packing properties of the entire lipid assembly in the membrane to enable tafazzin to catalyse the remodeling of cardiolipin by combinations of forward and reverse transacylations, essentially creating an equilibrium distribution of acyl groups. The shape of tetralinoleoyl-cardiolipin is such that it fits the geometry of negatively curved monolayers particularly well so this structure is favoured.

It seems that we now have a good understanding of the nature of the complex phytoglycosphingolipids from higher plants, although much remains to be learned of their biochemistry and especially their function. However, following the recent discovery of inositol phosphorylceramide glucuronosyltransferase 1, i.e. the first enzyme in the GIPC glycosylation pathway, it has now been shown that these highly polar membrane lipids are essential for normal growth and function in Arabidopsis (Tartaglio, V. et al. Glycosylation of inositol phosphorylceramide sphingolipids is required for normal growth and reproduction in Arabidopsis. Plant J., 89, 278-290 (2017);   DOI).

March 29th, 2017

Scottish thistleProfessor Roscoe O. Brady (1923-2016) will long be revered as one of the pioneers of research into the sphingolipidoses and especially Gaucher's disease. In large part through his efforts, an effective enzyme replacement therapy has been developed for one form of this disease. As part of a Festschrift in his honour in the journal Molecular Genetics and Metabolism, his many colleagues have published their personal reminiscences and insights into his accomplishments (Desnick, R.J. et al. Roscoe Owen Brady, MD: Remembrances of co-investigators and colleagues. Mol. Gen. Metab., 120, 1-7 (2017);  DOI). This tribute is accompanied by a number of further papers relevant to this topic.

According to Nature News ([Link]), the Gates Foundation has announced a new open-access publishing venture modeled on that of the Wellcome Trust. The open-access movement in general seems to be gaining momentum, a boon to someone like myself who has more limited access to journals than those with university positions. In the biological sciences, we tend to be more fortunate than those whose primary interest is chemistry, but there are occasional backward steps. For example, the Biochemical Journal used to allow full access after one year - now 2013 is the last year to which this applies. The Journal of Lipid Research has just stopped access to papers in manuscript form ahead of publication, although I assume that they will still be available one year after publication. I don't recall seeing any formal announcements of these changes.

March 22nd, 2017

Proteolipids are protein lipid conjugates in which the lipid portion is necessary to direct the protein to a membrane where it is required for a specific function. Many of these are signalling proteins (e.g. receptors, G-proteins, protein tyrosine kinases) with implications for the relevant signalling events at the cell surface, and many influence human disease states and are potential pharmacological targets. For example, deregulation of S-palmitoylation has been associated with heart disease, cancer, mental retardation and schizophrenia. A correspondent has brought to my attention a new website that is both informative and elegantly designed that covers the topic of S-palmitoylation, i.e.

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a very different type of protein-lipid complex. The protein component is α-lactalbumin, which is the most abundant protein in human breast milk and normally exists in a tightly packed globular conformation stabilized by four disulfide bridges and a divalent calcium ion. The lipid is oleic acid, and this is not linked covalently but by nonspecific hydrophobic interactions in the loosely organized hydrophobic core of the protein when it is in a molten globular state, as is produced during casein precipitation at low pH. The HAMLET complex can be internalized into cancer cells where it initiates a series of metabolic changes that can result in cell death. In human clinical studies, HAMLET has been shown to be efficacious against skin papillomas and bladder cancers, as well as against many other cancers in animal models. A new review summarises progress with this fascinating molecular complex (Ho, J.C.S. et al. HAMLET - A protein-lipid complex with broad tumoricidal activity. Biochem. Biophys. Res. Commun., 482, 454-458 (2017);  DOI).

A title such as "Masochistic Enzymology: Dennis Vance's Work on Phosphatidylcholine" should catch the eye of most readers. To find what it means, follow this Link to a brief open access commentary in the Journal of Biological Chemistry.

March 15th, 2017

Oxidized phospholipids are important biological mediators, and it is increasingly being recognized that oxylipins of various kinds are esterified to glycerophospholipids, which may serve in part as reservoirs from which they can be released rapidly upon stimulation by various means or the oxidized glycerophospholipids may have biological activities of their own. This is perhaps more surprising when oxylipins formed by non-enzymatic means are concerned, but there appears to be ample evidence that isoprostanes can act in this way. For example, an oxidized species derived from sn-2-arachidonoyl phosphatidylcholine has been shown to modulate the expression of a large number of genes in human aortic endothelial cells, and it is also a potent activator of the peroxisome-proliferator-activated receptor (PPARα).

Similarly, phospholipids that have been oxidatively cleaved to produce "core-aldehydes" have biological activities that resemble those of platelet-activating factor, while other related phospholipids interact with receptors that are normally associated with the recognition of microbial pathogens, as discussed in separate web pages.

Phosphatidylcholine is the most common phospholipid in animal cells, and it is not recognized by any pattern-recognition receptors in native low-density lipoproteins (LDL) or on the surface of cells. However, once oxidized it becomes a key ligand that, for example, mediates the binding of oxidized LDL to receptors, which are normally believed to have very different binding characteristics in relation to microbial pathogens. A concept has been developed of the formation of damage-associated molecular patterns (DAMPs) that arise from the oxidative damage of lipids and lipoproteins. These share common structural motifs with microbial pathogen-associated molecules, and so they activate the same pattern-recognition receptors that are present on the surface of macrophages and of immune and vascular cells. This enables them to initiate many different inflammatory signalling processes. A new review deals with this topic (Miller, Y.I. and Shyy, J.Y.J. Context-dependent role of oxidized lipids and lipoproteins in inflammation. Trends Endocrinol. Metab., 28, 143-152 (2017);  DOI).

Most work on this problem has been concerned with phosphatidylcholine, but a new analytical study has examined the nature of the oxidized phosphatidylinositol in LDL. Of course, there is much less of this phospholipid but it is highly unsaturated so it may make a sigificant contribution to oxidative stress (Hasanally, D. et al. Identification of oxidized phosphatidylinositols present in OxLDL and human atherosclerotic plaque. Lipids, 52, 11-26 (2017);   DOI). Now, the knowledge of what is there should be a stimulous to biological studies

March 8th, 2017

The latest Fats of Life Newsletter was a welcome arrival in my email inbox this week. In addition to the usual section on highlights from the recent literature, it contains two original articles of which I can certainly recommend that entitled "F3-isoprostanes and F4-neuroprostanes: non-enzymatic cyclic oxygenated metabolites of omega-3 polyunsaturated fatty acids: biomarkers and bioactive lipids" (by Galano, G.M. and 7 others), as it will be helpful in updating my web pages here.

When I do my weekly search for new lipid analysis publications, I try to list only those that demonstrate something that is truly new either in terms of the methodology or the sample under analysis. Nowadays, the result is a list of papers dealing mainly with mass spectrometry of lipids, which generally show only minor improvements on what has gone before. Please do not think that I am being disparaging here, as this is how science usually works. Only rarely do I find a publication that marks a step forward simply in chromatography terms these days, but a new paper describing the separation of regio-isomers of triacylglycerols by reversed-phase HPLC seems to fall into this category (Sompila, A.W.G.T. et al. Fast non-aqueous reversed-phase liquid chromatography separation of triacylglycerol regioisomers with isocratic mobile phase. Application to different oils and fats. J. Chromatogr. B, 1041, 151-157 (2017);  DOI). Although such separations have been demonstrated before with model mixtures, the methodology now seems to have reached a stage where it is applicable to natural samples.

I tend to take a cursory note only of new publications that deal with most clinical aspects of lipid science and leave these for others elsewhere to comment, as this topic lies outside my area of expertise. However, I can't resist a mention of a new paper (open access) dealing with sphingosine-1-phosphate (Soltau, I. et al. Serum-sphingosine-1-phosphate concentrations are inversely associated with atherosclerotic diseases in humans. PLOS One, 11, e0168302 (2016);  DOI). The authors demonstrate that decreased serum concentrations of this lipid are better markers of peripheral artery disease and carotid stenosis than is HDL cholesterol. Regretfully, I suspect that it will be some time before HPLC linked to tandem mass spectrometry becomes a routine screening tool for this purpose.

March 1st, 2017

Arachidonic acid is not present in higher plants, other than two species of Gymnosperms; I discount other alleged occurrences as not adequately characterized. However, it is present in lower plants such as algae, mosses and ferns. In a new systematic search for arachidonic acid in the plant kingdom (open access), the earlier findings were confirmed together with an inverse correlation between the concentration of this acid and that of the plant hormone jasmonic acid (Gachet, M.S. et al. Targeted metabolomics shows plasticity in the evolution of signaling lipids and uncovers old and new endocannabinoids in the plant kingdom. Sci. Rep., 7, 41177 (2017);  DOI). A further interesting discovery was the presence of two novel "endocannabinoid-like" molecules derived from 5,11,14,17-eicosatetraenoic or juniperonic acid, an omega-3 structural isomer of arachidonate, namely juniperoyl ethanolamide and 2-juniperoyl glycerol in gymnosperms. I don't like the use of the term "endocannabinoid" in the title as this implies the existence of a specific receptor, but I can accept "endocannabinoid-like" from the abstract. Semantics aside, this seems to be an interesting report that may be relevant to the evolution of signalling pathways in plants.

A correspondent has brought a paper to my attention that demonstrates the occurrence of the systemic oxidative stress marker 8-isoprostane in sewage, with the suggestion that it may be a marker for general health in different populations; the authors report a 5-fold change from three sewage collection points supplied by different communities located in the Detroit metropolitan area (Santos, J.M. et al. Could sewage epidemiology be a strategy to assess lifestyle and wellness of a large scale population? Medical Hypotheses, 85, 4080411 (2015);  DOI). Whatever the answer to the question posed by the authors, it is a novel application of lipid analytical methodology and a tribute to its sensitivity.

February 22nd, 2017

Scottish thistle Gangliosides are essential constituents of the central nervous system and of some non-neural tissues. They are arguably the least lipid-like of all animal lipids, by some definitions at least, in that they are as soluble in water as in many of the organic solvents used for extracting lipids from tissues. The hydrophobicity is due to a complex oligosaccharide component to which highly polar sialic acid units are attached, i.e. N-acetylneuraminic acid and its metabolite N-glycolylneuraminic acid, which differ only by the presence of one oxygen atom in the acyl moiety. Both sialic acids are present in nearly all animal species including other primates such as the great apes. Humans are the sole exception in that they lack gangliosides containing N-glycolylneuraminic acid. We have the genes that are required to produce this, but they have been irreversibly silenced. As far as I am aware, this is the only important biochemical distinction between humans and apes, and it is regarded as a major biochemical branch-point in human evolution. It may even be a factor in the superior performance of the human brain. We cannot test evolutionary hypotheses, but the relevance of gangliosides containing N-glycolylneuraminic acid to brain function can be tested in experimental animals at least as in a new publication (Naito-Matsui, Y., et al. Physiological exploration of the long term evolutionary selection against expression of N-glycolylneuraminic acid in the brain. J. Biol. Chem., 292, 2557-2570 (2017);  DOI). The results show that in transgenic mice in which expression of N-glycolylneuraminic acid was enhanced in the brain, the consequence was "abnormal locomotor activity, impaired object recognition memory, and abnormal axon myelination"; the transgenic mice were also lethally sensitive to a specific bacterial toxin. Whatever caused this evolutionary change appears to have done us a favour. The paper is an editor's choice and is open access.

There is a new paper entitled "Localized aliphatic organic material on the surface of Ceres" (De Sanctis, M.C. et al. Science, 355, 719-722 (2017);  DOI). Or see the more accessible report in Sci-News. Are there fatty acids in space?

February 15th, 2017

The isoprostanes are fascinating lipid mediators produced by non-enzymatic mechanisms that closely resemble the prostaglandins in structure. Indeed, so close is the similarity that it has been suggested that during evolution, the first primitive animals found these molecules so useful for signalling purposes that they developed enzymatic methods to produce analogues on demand in response to specific stimuli. Because of their formation by simple chemical reactions, one major difference is that the isoprostanes are produced as many different structural and stereo-isomers, while prostaglandin synthesis is highly stereospecific. Another important difference is that isoprostanes are produced while esterified to complex lipids in membranes, while prostaglandins are synthesised as the free acids. The latter fact is attracting special interest now as it has become apparent that lipid-bound isoprostanes are involved in many biological reactions, in part simply by causing disruption to membranes but also by highly specific interactions with receptors and proteins in general. A new review suggests that phosphatidylcholines containing isoprostanes with an cyclopentenone structural motif are potent pro-resolution mediators like the protectins, resolvins and maresins. In this instance, the cyclopentenone unit, an electrophilic α,β-unsaturated carbonyl moiety, can form covalent adducts with cysteine residues by Michael addition. Then, activation of the antioxidant response factor Nrf2 in this way might be one of a number of reasons for the anti-inflammatory effects (Friedli, O. and Freigang, S. Cyclopentenone-containing oxidized phospholipids and their isoprostanes as pro-resolving mediators of inflammation. Biochim. Biophys. Acta, 1862, 382-392 (2017);  DOI).

This review is part of a special issue of Biochim. Biophys. Acta - Molecular and Cell Biology of Lipids (Volume 1862, Issue 4, Pages 369-440 (April 2017)) dealing with the topic of "Lipid modification and lipid peroxidation products in innate immunity and inflammation" (edited by Christoph J. Binder).

February 8th, 2017

I have mentioned JOVE-Journal of Visualized Experiments before in this blog. It contains laboratory protocols for many types of analytical method, and is unique in that it supplements the written procedures with online videos showing in detail how to go about each analysis. Happily, it is also largely open access. Nowadays, I am an armchair scientist, but I enjoy viewing these videos, if only to see how others go about procedures with which I have some familiarity. Often they use different types of glassware, or equipment for handling samples with which I am not acquainted. I sometimes bring them to the attention of my former colleagues, not so that they should change how they go about things but simply to give them a fresh viewpoint. Two recent publications from this journal are relevant to my past research interests (Ginies, C. et al. Identification of fatty acids in Bacillus cereus. J. Vis. Exp., 118, e54960 (2016);  DOI; and Quideau, S.A. et al. Extraction and analysis of microbial phospholipid fatty acids in soils. J. Vis. Exp., 114, e54360 (2016);  DOI). Although both topics may appear rather specialized at first glance, many aspects of the methodology have more general applications. For example, the first illustrates the preparation of dimethyloxazoline (DMOX) and 3-pyridylcarbinol esters of fatty acids for mass spectrometry, while the second shows how to prepare a phospholipid fraction by solid-phase extraction methodology. There are some parts of both publications that I might prefer to do differently, but they are very useful guides for the novice while the expert can always learn something new.

February 1st, 2017

Studies of the occurrence and biochemistry of nitro adducts of unsaturated fatty acids only started in a systematic way in 1999 with the discovery that were present in the membrane phospholipids of human tissues in vitro and in vivo, and at concentrations that had the potential to exert biological effects. Now, their biology is a highly dynamic subject, not least because it has been demonstrated that they afford protection from inflammatory injury in several experimental models and so have therapeutic potential. In addition, they are electrophiles with a propensity to undergo reversible Michael addition reactions with cellular nucleophiles such as cysteine and histidine-containing peptides and proteins with further effects upon metabolism. While many different fatty acids can act as precursors, it has become evident that conjugated linoleate (CLA) isomers are by far the most active. A new important paper on the topic is a mechanistic and kinetic study of the reaction of CLA with thiols in the Journal of Biological Chemistry; it is the editor's choice and is therefore open access (Turell, L. et al. The chemical basis of thiol addition to nitro-conjugated linoleic acid, a protective cell-signaling lipid. J. Biol. Chem., 292, 1145-1159 (2017); DOI). Amongst many interesting findings, CLA reacts rapidly with thiols occur form adducts both β and δ to the nitro group, especially the latter. Indeed, the cysteine-δ-adducts have been detected in human urine.

Another paper from the same group (also open access) describes how nitro-fatty acids are catabolized and eliminated from the body in the urine. The main metabolite is 4-nitro-octanedioic acid (NO2-8:0-diCOOH) (Salvatore, S.R. et al. Evaluation of 10-nitro oleic acid bio-elimination in rats and humans. Sci. Rep., 7, 39900 (2017);   DOI). Stop Press: the February issue of the Journal of Lipid Research will contain a paper on the metabolism of nitro fatty acids in adipose tissue.

January 25th, 2017

Scottish thistleA special issue of the journal Neuropharmacology (Volume 113, Part B, Pages 595-672, 2017) is devoted to the topic of "Lipid Sensing G Protein-Coupled Receptors in the CNS" (edited by Kumlesh K. Dev and Andrew J. Irving). One review that interested me especially deals with sphingosine-1-phosphate metabolism in relation to health. (O'Sullivan, S. and Dev, K.K. Sphingosine-1-phosphate receptor therapies: Advances in clinical trials for CNS-related diseases. Neuropharmacology, 113, 597-607 (2017)). The realization that this lipid is involved in many different metabolic diseases has lead to the development of a number of new drugs with great therapeutic potential. In particular, a molecule derived synthetically from considerations of the structures of sphingoid bases and termed 'fingolimod (or FTY720)' has been approved by the Food and Drug Administration (USA) as an oral treatment for relapsing and remitting multiple sclerosis, a condition caused by an autoimmune attack on the myelin sheaths of nerves. Within affected tissues, fingolimod is phosphorylated by sphingosine kinase 2 and the resulting fingolimod-phosphate is released from cells as an agonist for sphingosine-1-phosphate receptors to cause immunosuppression. In addition, I learned that this drug has reached the phase II stage in clinical trials for amyotrophic lateral sclerosis, acute stroke and schizophrenia, and the phase I stage for Rett syndrome and glioblastoma, while pre-clinical studies suggest that it may be of value for a number of other diseases including Alzheimer's, Parkinson's and Huntington's diseases.


I have few regrets about retirement from my research post, though I sometimes wish I had had access to some of the newer instrumental methodologies. For example, mass spectrometry with electrospray ionization would have been a great boon. Similarly, I would love to have been able to use the modern counter-current chromatography equipment, which fits onto a bench top. When I was a post-doc at the Hormel Institute in the 1960s, they had a massive all-glass instrument that filled a room to do the same job and required vast quantities of solvent. The modern equivalent would have been ideal for studies of lipid mediators in plants, for example. I can recommend a new paper from Vetter's lab that shows what can be achieved with some lipids (Hammann, S. et al. More than 170 polyunsaturated tocopherol-related compounds in a vitamin E capsule: Countercurrent chromatographic enrichment, gas chromatography/mass spectrometry analysis and preliminary identification of the potential artefacts. J. Chromatogr. A, 1476, 77-87 (2016); DOI).

January 18th, 2017

The Nature Publishing Group has brought a large number of new scientific journals in many disciplines onto the market in recent years, many internet only. I had thought that with the stresses on library budgets, the market was saturated with journals, but apparently not. Regretfully I have very limited access to any of these. One exception is Scientific Reports, which is open access and where I have found a number of interesting publications in recent months. For example, one such is a paper in which mass spectrometric imaging has been used to look at the changes in lipid content during cerebral ischaemia. The authors were able to watch how a number of bioactive lipid mediators, normally present at very low levels, accumulated in specific cells types from the initial phase of inflammation and tissue injury through to the later phase of resolution and repair (Nielsen, M.M.B. et al. Mass spectrometry imaging of biomarker lipids for phagocytosis and signalling during focal cerebral ischaemia. Sci. Rep., 6, 39571 (2016); DOI). It appears to me to be a good example of how good analytical work can reveal how lipids function and point the way forward to biochemists.

A special issue of the Journal of Molecular Biology (Volume 428, Issue 24, Part A, Pages 4737-4866 (2016)) deals with the topic of "Molecular Biology of Membrane Lipids" edited by Kai Simons and Ünal Coskun. For my purposes, several papers dealing with sphingolipids are of particular interest

January 11th, 2017

I recently came across a blog dealing with microbiology (Small Things Considered), in which one article started with the words "The Lipids That Last Forever - The world of lipids does not always gets its due. Their oleaginous charm is not always appreciated". An earlier article from this blog started with the sentence "In the beginning, there were fats, and in the end, only fats will remain". It is not surprising that both caught my immediate attention. The lipids in question are hopanoids, and I came across the blog when I was updating my article here on the subject. If you are unfamiliar with these compounds, they are pentacyclic structures produced mainly by bacteria that are similar to sterols and indeed have been called 'sterol surrogates', as they perform similar roles to sterols in membranes. The reason they live for ever is that the ring structures are highly stable to chemical degradation, so geochemists tend to look upon them as molecular fossils ('geohopanoids') that serve as biological markers for particular organisms in geological formations from recent sediments to petroleum deposits and rocks. For example, they have been found in 2.7 billion year old shales in Australia. In one estimate, their mass in sedimentary rocks and oil reservoirs is said to be ~1012 tons, an amount comparable to the total mass of carbon in all living organisms! They may therefore be the most abundant lipids on earth.

What is the most abundant lipid class in living organisms on earth? Two suggestions come to mind from the world of plants - first the layer of wax that covers the surfaces of all leaves, and secondly the galactosyldiacylglycerols that are major constituents of the photosynthetic membranes in all plants. Then, I have read somewhere that the total living microbial biomass, including that in the oceans, soils and sediments, is greater than that of plants and animals, so perhaps a microbial lipid - possibly phosphatidylethanolamine - is more abundant. I will leave others to do the calculations.

January 4th, 2017

A fascinating new publication describes a method by which the complex lipids in the outer leaflet of the plasma membrane can be replaced in intact cells in culture. Methyl-α-cyclodextrin loaded with lipids effects a rapid exchange with the membrane lipids without removing any of the cholesterol that might otherwise cause membrane disruption (Li, G.T. et al. Efficient replacement of plasma membrane outer leaflet phospholipids and sphingolipids in cells with exogenous lipids. Proc. Natl. Acad. Sci. USA, 113, 14025-14030 (2016); DOI). The initial results were broadly as expected and confirmed that 70-80% of cell sphingomyelin resides in the plasma membrane outer leaflet and that the phosphatidylcholine in this membrane contains less unsaturated fatty acids than that in the remainder of the cell. However, the main promise of this new technique is that it opens opportunities for studying the metabolism of living cells in which the membrane composition has been modified with exogenous lipids, including the use of non-natural synthetic lipids.

I spend much of my early research career at the Hannah Research institute in Ayr, which was then concerned with animal science in general and dairy animals in particular. We lived with the concern that animal rights activists might decend opon us at some time with the potential to do untold damage to our research and career development. When I moved to a plant research institute, I thought those troubles were behind me only to discover that I was now in danger from those fanatics who perceived that genetically modified crops would prove the end of mankind. Fortunately, they never troubled us in Dundee, and now the furore seems to have died down. Great strides have been made in recent years towards producing new oil-seed crops containing enhanced value both for industrial purposes and for the health of consumers. To this end, it has not been simply (!) a matter of introducing new desaturases, for example, but it has been necessary to modify many aspects of the biosynthetic machinery. An open access publication provides an excellent account of this new technology (Haslam, R.P. et al. Synthetic redesign of plant lipid metabolism. Plant J., 87, 76-86 (2016); DOI).

December 28th, 2016

Scottish thistleLike many of my readers, I have been enjoying a relatively lazy time over the holiday period with too much food and television and too little exercise. This web site has been largely but not entirely neglected, and I have found one open access article that those of you with an interest in the fat-soluble vitamins and vitamin A especially will want to read (Chelstowska, S. et al. Molecular basis for vitamin A uptake and storage in vertebrates. Nutrients, 8, 676 (2016); DOI).

I have also found an analysis paper of interest in that it demonstrates a separation that has always been rather difficult if not impossible, i.e. of monogalactosyl- and monoglucosyl-diacylglycerols. Advances in analytical methodology often lead to advances in other areas, so this should enable better opportunities for metabolic studies of these lipids (Shan, Y.B. et al. Lipid profiling of cyanobacteria Synechococcus sp PCC 7002 using two-dimensional liquid chromatography with quadrupole time-of-flight mass spectrometry. J. Sep. Sci., 39, 3745-3753 (2016); DOI).

December 21st, 2016

While innumerable benefits of fatty acids to aspects of human health have been demonstrated over the years, it is also true that many studies have shown the importance of fatty acid biosynthesis for cancer cell growth and survival. Rapidly growing tissues, such as cancer cells, have a high demand for fatty acids for membrane biogenesis and as a source of energy. They are also required for the synthesis of key lipids in mitochondrial oxidation such as cardiolipin, for protein acylation and for the production of lipid mediators. In consequence, there are ongoing attempts to target the fatty acid synthase and its regulatory elements with the hope of therapeutic benefits, so far without success, in part because of uptake of these metabolites from other tissues. Another important enzyme in this context is stearoyl-CoA desaturase, which introduces a double bond with formation of oleate. A fascinating new review, which happily is open access, describes all these factors together with the opportunities for influencing them by pharmaceutical intervention (Röhrig, F. and Schulze, A. The multifaceted roles of fatty acid synthesis in cancer. Nature Rev. Cancer, 16, 732-749 (2016); DOI).

The fertility regulator in the UK has decided to allow the birth of babies from embryos modified to contain the DNA of three people in “certain, specific cases” making us the first country to explicitly permit the therapy. Their press statement says “Today’s historic decision means that parents at very high risk of having a child with a life-threatening mitochondrial disease may soon have the chance of a healthy, genetically related child. This is life-changing for those families.” I hope that we will never again see a brave boy suffering from the debilitating symptoms of Barth syndrome or a girl worrying that she may be a carrier.

I wish all my readers a very happy Christmas and a healthy and happy New Year.

December 14th, 2016

The November issue of the journal Biochimie (Volume 130, Pages 1-194) is devoted to the topic of 'Lipidomics and Functional Lipid Biology' and is edited by Hubert Schaller and Nicolas Vitale. There is a good mix of review articles including some on analysis, sphingolipids and many more. Having recommended a lipidomics review that dealt primarily with animal lipids last week, I must now redress the balance by citing a comparable review on the subject of plant lipids (Tenenboim, H. et al. Using lipidomics for expanding the knowledge on lipid metabolism in plants. Biochimie, 130, 91-96 (2016); DOI).

All lipids are subject to autoxidation, although as they tend to lack polyunsaturated fatty acid constituents I would not have expected this to be a serious problem. A quick perusal of my personal data base of references to analytical methodology picked up five publications only on the subject over the last 15 years. What caused me to look was a new paper on the oxidation of gangliosides, which drew my attention to the fact that carbohydrate moieties are also susceptible to oxidation (Couto, D. et al. New insights on non-enzymatic oxidation of ganglioside GM1 using mass spectrometry. J. Am. Soc. Mass Spectrom., 27, 1965-1978 (2016); DOI). The authors found that the ganglioside GM1 underwent oxidative cleavages in the carbohydrate chain with formation of other gangliosides GM2, GM3, asialo-gangliosides, smaller glycolipids and various oxygenated gangliosides and ceramides. These products could contribute to an imbalance of gangliosides metabolism in vivo and play some role in neurodegenerative processes.

The Cyberlipid website is a wonderful source of information on lipid structures, biochemistry and functions, which I check regularly when updating these pages, or which I simply browse through from time to time for my own satisfaction. This week I came across a record of a lipid class that was new to me at least although it has been known to others for more than 30 years - Lipo-chitooligosaccharides or nodulation factors (Nod factors), i.e. a class of signalling molecules produced by rhizobia that are essential for establishment of the nitrogen-fixing root nodule symbiosis with legume plants. In brief, they consist of a carbohydrate backbone with an amide linkage from glucosamine to an unusual fatty acid, such as 2E,9Z-hexadecadienoate. Suffice it to say, that it encouraged me to find a recent review and to add a few paragraphs on the subject in the Lipid Essentials section of this web site here.. While they should be classified as lipopolysaccharides, I have been unable to find them listed anywhere under this heading.

December 7th, 2016

There is a strong body of evidence, some derived from lipid studies, that during evolution the mitochondria in eukaryotes originated by symbiosis with a prokaryotic organism. For example, cardiolipin is found almost exclusively in certain membranes of bacteria (plasma membrane and hydrogenosomes), a few species of Archaea (haloarchaea) and mitochondria of eukaryotes, i.e. those membranes whose function is to generate an electrochemical potential for substrate transport and ATP synthesis. Further evidence comes from the findings that mitochondria in animals, including humans, and in yeasts contain type II fatty acid synthases, related to those in prokaryotes and entirely distinct from those of type I found in the cytoplasm. Indeed, the components of this enzyme, such as malonyl-CoA:ACP transferase, β-ketoacyl synthase and 2-enoyl-ACP reductase, were first identified by their similarity to the corresponding bacterial and yeast proteins and can be regarded as orthologs. A new review discusses the properties and function of this mitochondrial enzyme, which is known to be essential for cellular respiration and mitochondrial biogenesis and may be involved in many aspects of the coordination of intermediary metabolism in eukaryotic cells (Kastaniotis, A.J. et al. Mitochondrial fatty acid synthesis, fatty acids and mitochondrial physiology. Biochim. Biophys. Acta, 1862, 39-48 (2017); DOI).

This article is part of a Special Issue of the journal Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (Volume 1862, Issue 1, January 2017), which is entitled "Lipids of Mitochondria" (edited by Guenther Daum) and includes a number of other fascinating reviews.

As an armchair scientist, I find it hard to keep up with the modern mass spectrometric techniques that are applied to lipidomics. Puzzling new acronyms for variations in the methods seem to appear every month. There has been no shortage of reviews on this subject in the current year, but it is impossible to read them all. What can I recommend then? I like a new review from Xianlin Han, the co-author of the most recent edition of my book 'Lipid Analysis'. It is well written, authoritative, up-to-date and has a useful glossary to remind me of the definitions of many of the technical terms. I was intrigued to learn that the methodology is now sufficiently sensitive to analyse the lipids of single cells - it seems that the main problem now is how to handle single cells! (Yang, K. and Han, X. Lipidomics: techniques, applications, and outcomes related to biomedical sciences. Trends Biochem. Sci., 41, 954-969 (2016); DOI).

November 30th, 2016

Scottish thistleChiral chromatography has long been recognized as an invaluable tool for the isolation and characterization of eicosanoids and related oxylipins. It has also been used to separate chiral di- and monoacyl-sn-glycerol derivatives produced as part of procedures for stereospecific analysis of triacyl-sn-glycerols. However, applications to intact lipids are relatively scarce. A new publication demonstrates some remarkable separations of triacyl-sn-glycerols containing polyunsaturated fatty acids, including synthetic standards and natural algal samples (Rezanka, T. et al. Enantiomeric separation of triacylglycerols containing polyunsaturated fatty acids with 18 carbon atoms. J. Chromatogr. A, 1467, 261-269 (2016); DOI).

A second new paper demonstrates separations of intact phosphatidylcholines containing chiral hydroperoxides derived from linoleate that are just as notable. If these are formed by autoxidation, two enantiomers are formed in equal amounts, which can now be resolved by chiral chromatography, but if they are formed enzymatically, only a single enantiomer is seen. It is therefore possible to distinguish between enzymatic and auto-oxidation (Ito, J. et al. A novel chiral stationary phase HPLC-MS/MS method to discriminate between enzymatic oxidation and auto-oxidation of phosphatidylcholine. Anal. Bioanal. Chem., 408, 7785-7793 (2016); DOI). As it now appears that phospholipids containing oxylipins may have some biological activity in their own right, I can foresee further useful applications of this methodology.

November 23rd, 2016

The must-read publication of the week is happily open access and is an autobiographical account of his career and research by Professor Edward Dennis (Dennis, E.A. Liberating chiral lipid mediators, inflammatory enzymes, and LIPID MAPS from biological grease. J. Biol. Chem., 291, 24431-24448 (2016); DOI). It covers a fascinating period in lipid science, when it first became apparent that chiral lipid molecules were just as capable of encoding specific and unique biological information as other natural organic molecules. Stemming from his work on phospholipases, which release so many of the oxylipin precursors, he was among the first to recognize that lipids have a central role in cell signalling. With the creation of the LIPID MAPS initiative in 2003, he was at the forefront of establishing the importance of lipidomics to so many aspects of human metabolism. I am always fascinated by personal accounts of this kind that describe what stimulated particular research directions as well as telling a very human story.

One of the important aspects of the WOW is the ease with which articles can be updated, and I do my best to ensure that my articles in the Lipid Essentials section are kept as current as possible. I keep a simple list of my improvements to each article, and from time to time I check the literature to see whether anything of importance has been omitted. Last week I noted that only one page had not been updated at all this year, i.e. that on the glycosyldiacylglycerols of animal as opposed to plant origin. With that in mind, I did a citation search using some key references but found no new publications that were relevant to my account of the topic. For example, an important paper on the structure of the digalactosyldiacylglycerols of animal tissues from 2001 had been cited only 6 times since. A key paper on seminolipid of a similar vintage had been cited more often, but I found nothing new to explain the functional properties of this lipid at a cellular level. One problem with the analysis of neutral galactosyldiacylglycerols is that they occur at low levels in tissues relative to sphingolipids, which are often concentrated prior to analysis by a mild transesterification process that removes glycerolipids. I'll keep hoping for more.

I recently had a fascinating correspondence with someone with concerns about the use of potentially hazardous solvents in lipid analysis. There is no single solution, but increasing use of sealed instrumental methods and robotics may be one way forward. Aided by the sensitivity of modern mass spectrometric methods, another approach is to miniaturize such procedures as lipid extraction as proposed in a new publication (Panchal, S. et al. Ionic liquid based microextraction of targeted lipids from serum using UPLC-MS/MS with a chemometric approach: a pilot study. RSC Adv., 6, 91629-91640 (2016); DOI). As an arm-chair warrior these days, I cannot follow up such studies myself.

November 16th, 2016

Three weeks ago in this blog, I discussed the bacterial isoprenoid lipid II. This molecule is probably of little interest to main-stream lipid scientists, but its biosynthesis is considered a potential target for the development of novel antibiotics. I make no claims to clairvoyance, but a new publication demonstrates that this is indeed a realistic possibility (Cochrane, S.A. et al. Antimicrobial lipopeptide tridecaptin A1 selectively binds to Gram-negative lipid II. Proc. Natl. Acad. Sci. USA, 113, 11561-11566 (2016); DOI). The tridecaptins, isolated from strains of Paenbacillus polymyxa, are linear cationic tridecapeptides with a combination of L- and D-amino acids that are acylated with β-hydroxy fatty acids. They show strong activity against Gram-negative bacteria, exerting their bactericidal effect by binding to the cell-wall precursor lipid II on the inner membrane, disrupting the proton motive force. As their toxicity is relatively low and preliminary experiments show that bacteria do not appear to develop resistance, they are considered strong candidates for therapeutic use.

The open access journal Nature Communications has recently published two papers of particular interest to lipid scientists. In the first, N-docosahexaenoylethanolamide or 'synaptamide' has been found to have its own receptor, i.e. the orphan G-protein-coupled receptor GPR110 (ADGRF1). It binds specifically to this and triggers cAMP production and signalling with low nM potency, with the effect of inducing neurogenesis, neuritogenesis and synaptogenesis in developing neurons. It is a further mechanism by which DHA promotes brain development and function (Lee, J.W. et al. Orphan GPR110 (ADGRF1) targeted by N-docosahexaenoylethanolamine in development of neurons and cognitive function. Nature Commun., 7, 13123 (2016); DOI). It is intriguing how this and the arachidonoyl, palmitoyl, oleoyl and stearoyl ethanolamides have such diverse biological functions (see our web page on simple amides). The second paper also relates to a metabolite of DHA. In relation to atherosclerotic plaques, it is reported that the deleterious effects of leukotriene LTB4 resulting from an excessive inflammatory response are countered by the presence of specialized proresolving mediators, especially resolvin D1 (RvD1), which are derived from DHA, suggesting a new therapeutic approach to promote plaque stability (Fredman, G. et al. An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques. Nature Commun., 7, 12859 (2016); DOI).

I have just come across a new definition - 'ectopic lipids', which appears to be another name for the lipids in the small fat droplets found in tissues other than adipocytes (Loher, H. et al. The flexibility of ectopic lipids. Int. J. Mol. Sci., 17, 9 (2016); DOI; open access).

November 9th, 2016

In my Lipid Essentials section, I have discussed the effects of oxidized phospholipids in a number of different web pages. For example, the oxidatively truncated phospholipids are treated under platelet-activating factor, while others are dealt with under the headings Isoprostanes and Bioactive aldehydes. However, it can be useful to see the various aspects of the biochemistry of these important lipid molecules, which can have pro- or anti-inflammatory activities depending on their chemical structures and cellular location, reviewed together in a single coherent account. A recent review that is open access does just that (Freigang, S. The regulation of inflammation by oxidized phospholipids. Eur. J. Immun., 46, 1818-1825 (2016); DOI).

Last week, I discussed the potential therapeutic importance of synthetic lipids such as edelfosine. I have just encountered a review describing how it may function in lipid rafts, i.e. highly ordered membrane domains that are enriched in cholesterol and sphingolipids and act as sorting platforms for molecules involved in signal transduction. Among other aspects, it is suggested that "edelfosine shows a high affinity for cholesterol and accumulates in lipid rafts in a number of malignant hematological cells, leading to an efficient in vitro and in vivo antitumor activity by inducing translocation of death receptors and downstream signaling molecules to these membrane domains." This may be a mechanism for its anti-cancer activities (Mollinedo, F. and Gajate, C. Lipid rafts as major platforms for signaling regulation in cancer. Adv. Biol. Reg., 57, 130-146(2015); DOI).

November 2nd, 2016

I have changed the title of this website from "LipidHome" to the "LipidWeb", as unfortunately the name "LipidHome" was already in use for a lipidomics software package. My aim in setting up this site was to demonstrate to AOCS how easy it was to change the structure of a website in a relatively short period - three weeks in fact. It was intended simply as a demonstration as AOCS had already spend two years, consultant costs and a huge amount of staff time to redesign the Lipid Library with no end in sight. I checked that the URL was available but did not check sufficiently for any other uses of my chosen title. As this site was not originally intended to last, this did not bother me to begin with. However, it now seems likely that the "LipidWeb" is going to last as long as I do - hopefully a few years yet. Hence the change of name. Unfortunately, changing the URL of the site is much more difficult, so I plan to leave it as it is for the moment. My sincere apologies to the original users of "Lipidhome".

In these pages, I tend to concentrate on naturally occuring lipids, their occurrence, chemistry, biochemistry and especially - function. However, there are occasons when natural lipids have inspired the design of synthetic compounds with valuable therapeutic properties so cannot be ignored. One such is 'edelfosine' (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) illustrated, which has obvious structural similarities to platelet activating factor. Other related molecules have the glycerol ether moiety attached to a carbohydrate, such as 'ohmline' (1-O-hexadecyl-2-O-methyl-rac-glycero-3β-lactose). These are proving to have valuable anti-cancer properties "that target cell membranes to induce apoptosis and to decrease cell migration/invasion, leading to the inhibition of tumor and metastasis development". Unfortunately, edelfosine per se seems to be too toxic for use in humans, but the new carbohydrate-containing analogues do not appear to have such problems. A new review discusses their potential clinical applications to prevent or treat tumor development and metastasis (Jaffres, P.A. et al. Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy. Pharm. Ther., 165, 114-131 (2016); DOI).

Formula of edelfosine

I have been writing this blog here and in the AOCS LipidLibrary for more than 10 years, and I have highlighted the plight of young researchers on many occasions. A new article in Nature News seems like deja vu - Young, talented and fed-up: scientists tell their stories. Why is nothing done about it? I suspect that Nature will be carrying similar stories 10 years from now.

October 26th, 2016

Scottish thistleFew lipid scientists, other than those concerned with microbial lipids, will have heard of lipid II or undecaprenyl diphosphate-MurNAc-pentapeptide-GlcNAc; it is more liked to be discussed in text books dealing with carbohydrates or proteins than with lipids. Yet, it is the last significant lipid intermediate in the construction of the peptidoglycan cell wall in bacteria with the important function of transferring the MurNAc-pentapeptide-GlcNAc monomer across the cell wall to form the complex peptidoglycan polymer that provides strength and shape to bacteria. The turnover rate is very high so the lipid II cycle is considered to be the rate-limiting step in peptidoglycan biosynthesis. Because of its highly conserved structure and accessibility on the surface membrane, synthesis and transport of lipid II is an important target for the development of novel antibiotics. As a new review points out, appreciable progress is being made towards this goal (Ng, V. and Chan, W.C. New found hope for antibiotic discovery: lipid II inhibitors. Chem. Eur. J., 22, 12606-12616 (2016); DOI).

It was rather unexpected to find a publication describing a completely new mechanism for targeting otherwise soluble proteins to membranes. Bacteria of the genus Mycoplasma are already unusual in that they have a very small genome, they lack a cell wall and they are obligate parasites that must obtain all their lipids from the host. Now, it has been demonstrated that in M. pulmonis an otherwise cytoplasmic protein, lacking signal peptides, is tethered to the outer membrane by a link from glutamine near the C-terminus of the protein to rhamnose and thence to a phospholipid, presumed for the moment to be phosphatidic acid. Whether other bacteria have a similar mechanism has yet to be determined (Daubenspeck, J.M. Rhamnose links moonlighting proteins to membrane phospholipid in Mycoplasmas. PLOS One, 11, e0162505 (2016); DOI;  open access).

October 19th, 2016

Two years ago, I discussed here a fascinating finding that fatty acids with a centrally located hydroxyl group to which a further fatty acid was linked as an estolide or 'FAHFA' (Fatty Acid Hydroxy Fatty Acid), such as the palmitoyl ester of 9-hydroxy-stearic acid, had been found in the adipose tissue of mice. They were reported to have anti-diabetic and anti-inflammatory effects, even when administered orally. Now, a new publication from the same group describes how branched fatty acid esters of hydroxy fatty acids protect against colitis by regulating gut innate and adaptive immune responses (Lee, J. et al. J. Biol. Chem., 291, 22207-22217 (2016); DOI). While it appears that little is yet known of their biosynthesis, it has been established that they are produced endogenously. Whatever their origin, they are an important addition to the range of lipids with therapeutic potential.

I have been enjoying the Thematic Review Series: Living History of Lipids, which is being published at intervals in the Journal of Lipid Research. The latest installment dealing with lipoproteins is no exception (Siri-Tarino, P.W. and Krauss, R.M. The early years of lipoprotein research: from discovery to clinical application. J. Lipid Res., 57, 1771-1777 (2016); DOI). Amongst other fascinating personal insights, it seems that after obtaining a medical degree John Gofman (together with his first graduate student Frank Lindgren, who I recall meeting 50 years ago) called upon his war-time experience of uranium isotope characterization to use ultracentrifuges for the first successful separation of serum lipoprotein classes. Their first publication on the subject was at first rejected summarily by the Journal of Biological Chemistry, before being accepted on appeal.

I have finally obtained a copy of the book by Gurr et al., mentioned in my last blog, via Amazon. I must say that it is superbly produced and the senior author must be congratulated on producing such a vital and uniform text from the contributions of multiple authors. So far, I have only dipped into it, but sufficiently for me to make some minor adjustments to some of my pages here already. Over the next few weeks, I expect to spend some time with it partly to check the accuracy of my own work, but mainly because it is always of interest to see how others with very different backgrounds approach the subject of lipid science.

October 12th, 2016

For the last week, I have been relaxing and enjoying the sunshine of the Canary Islands. No doubt the world of lipids is continuing to turn, and I hope soon to catch up with it. On my return from holiday, I found an email informing me that a long awaited book "Lipids: Biochemistry, Biotechnology and Health, 6th Edition" (by Michael I. Gurr, John L. Harwood, Keith N. Frayn, Denis J. Murphy and Robert H. Michell, ISBN: 978-1-118-50113-9, 448 pages, Wiley-Blackwell) is now available. I ordered a digital copy initially - my small contribution to saving the planet - but the publisher's website was so opaque and put so many impediments in my way that I will have to settle for the paper edition.

October 5th, 2016

From time to time, I come across a review publication that contains fascinating data on lipid functionality, although I am not clear how I can easily relate these to the documents in my Lipid Essential pages here. One such deals with CD1 molecules, i.e. a family of antigen-presenting glycosylated proteins that bind structurally diverse lipids and lipopeptides for the immune interaction with T cells (Zajonc, D.M. The CD1 family: serving lipid antigens to T cells since the Mesozoic era. Immunogenetics, 68, 561-576 (2016); DOI). These proteins exist in a large number of isoforms in which the shape and volume of the lipid binding groove can vary to suit different lipid antigens and how the CD1-lipid complexes are recognized by antigen receptors on T cells. The lipid antigens are often glycolipids of various kinds where the nature of the head group is of particular relevance. However, it also appears that the binding pocket can confer specificity according to the nature of the acyl groups, as monoacylated lipids or lipopeptides to tetra-acylated lipids are recognized with variable chain lengths and alkyl chain substitutions (double bonds, methylation, hydroxylation, cyclization). In part, this may explain the importance of particular molecular species of lipids.

In a visit to my local garden centre, I found that they already had set out a large Christmas display. It is not quite the same but as another sign of the times in my monthly literature survey, I have already one publication listed for 2017! Of course, this is due to online publication now, but presumably the relevant journal will not be sent out in print form until next year.

September 28th, 2016

Scottish thistleNature News section has just published an article under the heading "Mass production of review articles is cause for concern", suggesting that "a torrent of low-quality meta-analyses and systematic reviews in biomedicine might be hiding valuable research and misleading scientists - that much of the overall increase stems from articles intended mainly to increase citations and publications - or to serve as marketing tools for industry groups". Nowadays, I do not consider myself a specialist in any one area, but rather as a populariser of most aspects of lipid science or as a generalist. There is absolutely no way that I can keep abreast of the primary literature in such a wide field, so I am dependent on review articles to update these web pages. On the other hand, I have indeed had a vague sense that I was seeing a large number of reviews on similar topics, and to test this I have quickly checked the data base behind my literature survey pages for the Lipid Essentials section of this web site for the year 2015. I found 31 reviews on phosphoinositides, 5 on endocannabinoids, 11 on lysophospholipids, 15 on sphingosine-1-phosphate and 8 on ceramides. These are all dynamic areas, but 31 in one subject area does seem a bit excessive, even if this does encompass phosphatidylphosphoinositides, the water-soluble inositol phosphates, GPI-anchors for proteins, and animals versus plant metabolites (in fairness, there was a special journal issue on the topic that boosts the numbers). So far this year, there are a further 22 in this one area! The next problem is to decide which are the most useful, and I must have taken such a decision as I have cited just 7 of these in my document on phosphoinositides here - please don't ask why these and not any of the remaining 46.

That said, I am now going to recommend that you check out a new review - on phosphoinositides! This is now available ahead of formal publication in manuscript form and therefore open access (Irvine, R.F. A short history of inositol lipids. J. Lipid Res., in press; DOI). I find the history of such scientific topics both illuminating and entertaining, especially as I have lived and worked through the period without always recognizing the key milestones. The author's personal insights concerning the many scientists involved add greatly to the story.

My attention has been drawn to a new web site produced by John Ohlrogge of Michigan State University (USA), apparently as a post-retirement project: PhyloFAdb - "phylogenetic relationships between hundreds of fatty acids synthesized by thousands of plants". It contains a vast amount of data that will prove invaluable to all those with an interest in plant lipids. The data are easy to access via an elegant interface.

September 21st, 2016

Marine invertebrates contain a wide range of prostaglandins of the conventional type in addition to many novel prostanoids that differ in stereochemistry from the typical forms, or contain acetyl groups, or are substituted with halogen atoms, such as chlorine or bromine. They are presumed to perform similar functions as in mammals, but why should one species of coral (Plexaura homomalla) contains up to 8% of its dry mass as prostanoid esters? (For many years, this was a primary source of material for experimental work). It is perhaps more surprising that some red algae, better known as seaweeds, such as Gracilaria species contain prostaglandins (PGE2 and PGF) and are known to have a cyclooxygenase gene, although the function of these oxylipins in the organisms is unknown. As far as I am aware this is the only source of prostanoids from outwith the animal kingdom.

I was interested to see a new study of the molecular species composition of the glycerolipids from one species of this genus, i.e. mono- and digalactosyldiacylglycerols, sulfoquinovosyldiacylglycerol and phosphatidylcholine. The content of arachidonic acid in each lipid is remarkably high - up to 64%, so the source of the precursor to the prostaglandins is explained if not their function (Honda, M. Lipid classes, fatty acid composition, and glycerolipid molecular species of the red alga Gracilaria vermiculophylla, a prostaglandin-producing seaweed. J. Oleo Sci., 65, 723-732 (2016);  DOI;  open access). I suppose the best guess is that they operate in a similar manner to jasmonates in higher plants.

Monoenoic fatty acids with double bonds in even numbered positions are relatively rare in nature, with petroselinic acid (6-18:1) from seed oils of the Umbelliferae family and sapienic acid (6-16:1) from sebum being the obvious exceptions. A correspondent has now drawn my attention to the fact that 10-18:1 and 8-16:1 are considered specific for methane-oxidizing bacteria.

September 14th, 2016

A recent issue of the European Journal of Pharmacology (Volume 785, Pages 1-214, 15 August 2016) is devoted to the topic of "Immunopharmacology of fatty acids" (guest editors Philip C. Calder and Linette Willemsen). It deals largely with the biochemistry and functions of eicosanoids and docosanoids in health and disease. So far, I have only had the opportunity to browse rapidly through the contents, but I was pleased to see that some of the less obvious oxylipins were discussed at length, including those derived from linoleate, eicosapentaenoate and docosapentaenoate in addition to the better known resolvins and protectins derived from docosahexaenoic acid. I have a lot of reading to do!

The physical chemistry of lipids in membranes is an important topic that goes into scientific realms where I am soon left far behind, and that is especially true of a recent issue of Biochimica et Biophysica Acta (BBA) - Biomembranes (Volume 1858, Issue 10, October 2016) on the topic of "Biosimulations of lipid membranes coupled to experiments". However, I did find one short gem that I can recommend to a general lipid audience that discusses the molecular complexity of natural membranes and the experimental challenges ahead, where the tools of lipidomics will be especially relevant (Simons, K. Cell membranes: A subjective perspective. Biochim. Biophys. Acta, Biomembranes, 1858, 2569-2972 (2016); DOI).

The role of glycerol in the structure of plant cutins has been unclear, but a new study involving careful quantitative analysis has demonstrated that the molar ratio of glycerol to total dicarboxylic acids (DCA) in Arabidopsis cutins is 2:1, suggesting that glycerol-DCA-glycerol is the dominant structural motif (Yang, W. et al. Quantitative analysis of glycerol in dicarboxylic acid-rich cutins provides insights into Arabidopsis cutin structure. Phytochemistry, 130, 159-169 (2016); DOI). The key methodology was a stable isotope-dilution assay for the quantitative determination of glycerol by GC-MS of triacetin, together with simultaneous determination of the aliphatic monomers

September 7th, 2016

Further to my comment last week on links between the metabolism of sphingolipids and glycerolipids, I have been reminded that ceramide 1-phosphate (with phosphatidylinositol 4,5-bisphosphate) binds to the specific phospholipase A2 (cPLA2α) responsible for the hydrolysis of phosphatidylinositol to release arachidonic acid for eicosanoid production. It has stimulated me to add a new section to my web page Introduction to Sphingolipids, which I can update when new information becomes available.

Last week, the biological properties of 18:1 isomers came to the fore, and this week it is the turn of 16:1. Thus, 9-cis-hexadecenoic acid (palmitoleic acid, 9-16:1 or 16:1(n-7)) is a ubiquitous but normally minor component of animal lipids, and it has been found to have a distinctive function in mice as a lipokine - a newly coined word to define a lipid hormone, i.e. it is an adipose tissue-derived molecule, which amongst other effects stimulates the action of insulin in muscle. It is also an essential covalent modifier of Wtn proteins. Now an isomer cis-7-hexadecenoic acid (7-16:1 or 16:1(n-9)) is reported to be enriched in the lipids of foamy monocytes and to show significant anti-inflammatory activity; it may be a biomarker for early detection of cardiovascular disease (Guijas, C. et al. Foamy monocytes are enriched in cis-7-hexadecenoic fatty acid (16:1n-9), a possible biomarker for early detection of cardiovascular disease. Cell Chem. Biol., 23, 689-699 (2016); DOI). It is one of those minor fatty acids that is often ignored, overlooked or misidentified by analysts. I don't have access to this journal, but I was able to get a copy of the paper courtesy of the ResearchGate website.

Can we really consider formic acid to be truly a fatty acid, albeit the simplest of all? By some definitions, it is not even a lipid, but it is occasionally reported in esterified form in lipids. The latest is as a component of wax esters in an acarid mite (Shimizu, N. et al. Identification and synthesis of (Z,Z)-8,11-heptadecadienyl formate and (Z)-8-heptadecenyl formate: unsaturated aliphatic formates found in the unidentified astigmatid mite, Sancassania sp. Sasagawa (Acari: Acaridae). Molecules, 21, 619 (2016); DOI). The paper is open access.

August 31st, 2016

Scottish thistleA new publication demonstrates that N-cis-vaccenoylethanolamide (i.e. of 11-18:1) is the most abundant 18:1 fatty acylethanolamide in rat plasma and the second most abundant in human plasma (Rohrig, W. et al. Identification of the oleic acid ethanolamide (OEA) isomer cis-vaccenic acid ethanolamide (VEA) as a highly abundant 18:1 fatty acid ethanolamide in blood plasma from rats and humans. Anal. Bioanal. Chem., 408, 6141-6151 (2016); DOI). Its biological properties are as yet unknown, but hopefully will soon be explored. As there has been potential for confusion in some studies with the isomeric N-oleoylethanolamide, which is well-known for its effects as an endogenous regulator of food intake, some re-appraisal of the latter may also be required.

At the end of my presentation to the Scottish Lipid Group meeting last week, a questioner asked whether I knew of any links between glycerolipid and sphingolipid metabolism, other than sphingosine kinase 2 binding to phosphoinositides (which may facilitate its location to different membranes) and the provision of phosphorylethanolamine from sphingosine-1-phosphate catabolism for phosphatidylethanolamine biosynthesis. The obvious simple answer was that phosphatidylcholine is the precursor of sphingomyelin, but I was sure that there were other examples that I could not call to mind immediately. Having had time to check, I now have been reminded that the CERT protein involved in ceramide transport has a binding site for phosphatidylinositol 4-phosphate, while the ceramide kinase responsible for the biosynthesis of ceramide-1-phosphate requires phosphatidylinositol 4,5-bisphosphate to function. Of course, if there are other examples of which I am not aware, I would be grateful for enlightenment.

Stereospecific analysis of triacyl-sn-glycerols, i.e. the determination of the fatty acid compositions of each of positions sn-1, sn-2 and sn-3 of the glycerol moiety, can be a daunting task technically. There have been relatively few publications in recent years, possibly because of the concentration on modern mass spectrometric methodology for lipid analysis. However, regiospecific analysis only is possible by this means so positions sn-1 and sn-3 cannot be distinguished. There are two general approaches to full stereospecific analysis, both starting with the generation of random diacylglycerol species from triacylglycerols. The first uses enzymatic means to generate sn-1,2-diacylphosphatides as the basis for the reaction, while the second uses some form of chiral chromatography to separate the various enantiomeric diacylglycerol species. A good example of the first approach has now been published, in which the enzyme diacylglycerol acyl transferase from E. coli is used to generate an sn-1,2-diacylglycerophosphatide. Although the method was first described some years ago, it does not appear to have been used other than by the Italian originators. As the paper is open access and the method is illustrated rather well, I am happy to publicise it here (Cossignani, L. et al. Authentication of Coffea arabica according to triacylglycerol stereospecific composition. J. Anal. Chem., 7482620 (2016); DOI).

August 24th, 2016

Volume 199 (September 2016) of Chemistry and Physics of Lipids (pp. 1-186) is a substantial special issue dealing with "The Properties and Function of Cholesterol" (edited by Richard M. Epand and Amitabha Chattopadhyay). Much of it deals with the chemistry and physical chemistry of cholesterol in membranes, a topic which I have difficulties in digesting. However, there are two sections with a number of papers more relevant to my interests - "Cholesterol in biological membranes" and "Cholesterol and whole organism". I have only had time to read two of the papers in the latter, but I am sure they will be helpful in updating the sterol pages in my Lipid Essential section here.

It can be hard to determine when any scientific topic first became established, and this is certainly true of work on phosphoinositides. Was in the pioneering work on brain lipids by Folch in the 1940s, that of Mabel and Lowell Hokin in the 1950s, that of Bernard Agranoff in the 1960s, or that of several scientists in the 70s whose work could be cited for the discoveries on phosphoinosite signalling? Those interested in the early history of the subject will appreciate an autobiographical review published a few years ago by Agranoff (Turtles all the way: reflections on myo-inositol. J. Biol. Chem., 284, 21121-21126 (2009); DOI). Judging by the number of times I have updated my article on phosphoinositides on this site, work in this area is just as dynamic as ever. While plant scientists have lagged a little behind, they are catching up rapidly. A new paper demonstrates that phosphatidylinositol-4-phosphate is an important constituent of the plasma membrane in plant cells, where it controls the electrostatic state and is involved in cell division. It may control the location and function of many membrane proteins, including those required for development, reproduction, immunity, nutrition and signalling (Simon, M.L.A. et al. A PtdIns(4)P-driven electrostatic field controls cell membrane identity and signalling in plants. Nature Plants, 2, 16089 (2016); DOI).

August 17th, 2016

There has been enormous interest in the biologically active fatty acid amides and lipoamino acids in recent years, especially the endocannabinoids such as anandamide. However, I have only seen a few papers dealing with the N-acyl-taurine conjugates. A new publication may lead to renewed interest (Sasso, O. et al. Endogenous N-acyl taurines regulate skin wound healing. Proc. Natl. Acad. Sci. USA, 113, E4397-E4406 (2016); DOI). Potential receptors have been identified, and as the title suggests "an unprecedented lipid-based mechanism of wound-healing control in mammalian skin, which might be targeted for chronic wound therapy", especially when consequent to aging, diabetes, and immunosuppression, has been identified. The process is controlled by the fatty acid amide hydrolase, and in mouse skin two long-chain saturated N-acyl taurines, N-tetracosanoyl-taurine and N-eicosanoyl-taurine, are the primary substrates.

Formula of acyl-taurine

Transferring the results of animal studies to a clinical situation can be fraught with difficulties, but hopefully if the treatment can be applied directly to the skin this may not be a problem with acyl taurines. Clinical interventions with other potential lipid 'drugs' have not always proved successful. In my blog of three weeks ago, I discussed recent findings that α-galactosylceramides were potent endogenous stimulators of mammalian immune systems, and this is the topic of a new open access review (Carreño, L.J. et al. Synthetic glycolipid activators of natural killer T cells as immunotherapeutic agents. Clin. Translat. Immunol., 5, e69 (2016); DOI). The aim is to use these lipids or synthetic analogues to modulate the responses of natural killer T cell to improve immunity against infections and cancer. Unfortunately, this has not yet been achieved in humans, but it is hoped that improvements to the delivery systems may be the answer.

August 10th, 2016

Cardiolipin is a fascinating lipid for any number of reasons, but especially as a key component that binds to and activates three of the four enzymes involved in oxidative phosphorylation and the generation of ATP. It is a common constituent of bacterial membranes, but in animal tissues, it is in essence found only in mitochondria. This is often cited as confirmatory evidence for the evolutionary origin of mitochondria as bacterial cells engulfed by a eukaryotic organism. The picture was complicated relatively recently when this lipid was found in one group of the Archaea (haloarchaea). The biosynthetic mechanism differs between eukaryotes and bacteria, but this is now believed to be the result of convergent evolution. Now a publication has just come to my attention that suggests from protein domain analyses that the relevant biosynthetic enzymes in Eukarya arose by a chimeric event between the bacterial and archaeal pathways (Luévano-Martínez, L.A. The chimeric origin of the cardiolipin biosynthetic pathway in the Eukarya domain. Biochim. Biophys. Acta-Bioenergetics, 1847, 599-606 (2015); DOI).

Formula of cardiolipin

The structure is distinctive in that in essence it consists of two phosphatidic acid units linked by glycerol, i.e. it has four fatty acid components. In heart mitochondria, a high proportion of the fatty acids consists of linoleic acid so the molecule is relatively symmetrical, a feature that appears to be essential for its biological activity. This composition is attained post-synthesis largely by the action of a transacylase known as tafazzin. From a mathematical model based on the assumption that different molecular species have different free energies, it has been concluded that specific acyl-distributions in cardiolipin could arise from phospholipid transacylations in the tafazzin domain, even if tafazzin itself does not have substrate specificity. On the other hand, a new publication argues that the specificity is inherent in tafazzin per se in the model yeast Saccharomyces cerevisiae at least (Abe, M. et al. Mechanism for remodeling of the acyl chain composition of cardiolipin catalyzed by Saccharomyces cerevisiae tafazzin. J. Biol. Chem., 291, 15491-15502 (2016); DOI). Incidentally, a new study of the molecular species composition of cardiolipin in plants, shows that it contains mostly linoleic and linolenic acids (Zhou, Y.H. et al. Molecular species composition of plant cardiolipin determined by liquid chromatography mass spectrometry. J. Lipid Res., 57, 1308-1321 (2016); DOI).

August 3rd, 2016

Those with an interest in plant lipids will want to take note of a substantial review volume - Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Volume 1861, Issue 9, Part B, Pages 1205-1422 (September 2016) - devoted to the topic of "Plant Lipid Biology" and edited by Kent D. Chapman and Ivo Feussner. The various articles are grouped into three sections - "Lipid Synthesis and Turnover - Structural Lipids - Lipid Signalling".

I have only had a brief look at these myself so far, but I was intrigued by an article on pollen lipids (Ischebeck, T. Lipids in pollen - They are different. Biochim. Biophys. Acta, 1861, 1315-1328 (2016); DOI). To deliver the sperm cells from the stigma through the style to the ovule, a pollen tube must be produced rapidly that can be many centimeters in length and so requires vast amounts of lipid for membrane synthesis. These lipids include extraplastidial galactolipids and triacylglycerols stored in lipid droplets, together with special sterol and sphingolipid moieties that might together form raft-like domains in the membranes. Just last week, I came across another review dealing with a different aspect of lipid metabolism in pollen (Heilmann, I. and Ischebeck, T. Male functions and malfunctions: the impact of phosphoinositides on pollen development and pollen tube growth. Plant Reproduction, 29, 3-20 (2016); DOI). In this instance, the phosphoinositides have a critical regulatory function, controlling key steps in trafficking and polarization.

July 27th, 2016

Scottish thistleIt is apparent that increasing numbers of pathogenic bacteria are becoming resistant to antibiotics, and the search for replacements is a major task for the pharmaceutical industry and academia world wide. I suspect that it may become a recurring task for each generation of scientists. One area that looks promising and of relevance to lipid science is the field of antimicrobial lipopeptides. Some of these, such as the polymixins i.e. 7-membered cyclic peptides attached to a short linear peptide and thence to a fatty acid, are already being employed for the purpose. They are produced by Paenibacillus species and are effective against Gram-negative bacteria as they bind to the lipid A on the bacterial surface and render it innocuous. Unfortunately they are also somewhat toxic to humans, so can only be used for topical treatment of infections or as a last-line therapy against multi-drug-resistant Gram-negative bacilli. To counter these drawbacks, molecular biological methods and chemical synthesis are being used to create analogues with differing amino acid and fatty acid constituents as a new review explains (Velkov, T. et al. Polymyxins: a new hope in combating Gram-negative superbugs? Future Med. Chem., 8, 1017-1025 (2016); DOI - open access). So far, it appears that no new products have reached a commercial stage, but there is hope for the future.

Until relatively recently, galactosylceramides were though to possess only a β-D-galactosyl unit linked to ceramides, so it was somewhat of a surprise when epimeric α-galactosylceramides were found in a sponge and then in human gut microflora. Subsequently it was demonstrated that these were potent stimulators of mammalian immune systems by activating invariant natural killer T cells, one of the first pieces of evidence to show that glycolipids, like glycoproteins, could invoke an immune response. I have just been catching up on some elegant publications demonstrating that α-glycosylceramides are in fact produced endogenously in mammalian cells. Although they only amount to 0.02% of the total galactosylceramides, they are in fact the natural ligand for NKT cells in the thymus and the periphery (Kain, L. et al. Endogenous ligands of natural killer T cells are alpha-linked glycosylceramides. Mol. Immunol., 68, 94-97 (2015); DOI). How they are synthesised in animal tissues has still to be determined.

July 20th, 2016

I was delighted to learn that the Lipid Maps website ( is to move to the UK. The Wellcome Trust is providing more than £1M over 5 years to Cardiff University, Babraham Institute and UCSD to enable the transfer from the USA and presumably for the development of the site. The level of funding should permit the employment of permanent staff to work on the site, and I hope that this means more editorial content and news as occurred during the brief period when there was an involvement with Nature. It should also be a boost to the science of lipidomics in the UK. As it stands, the site is an invaluable font of information but not one I would visit for casual browsing; I hope this will change. Of course I am not envious, but I receive no salary for this website and the running costs of £50 per annum come out of my own pocket.

Two news items in Nature caught my eye this week. First, the Wellcome Trust is to establish a new open access journal to enable grantees to publish their research more quickly and free of cost. I will not duplicate the news item here but the new journal will have a novel peer review policy. Incidentally the Wellcome Trust already insists that grantees publish in open access journals.

The second news item concerns the sale of the Web of Science to a private equity company. The fear in such circumstances is that asset stripping will occur and prices will rise, though the article suggests that there may already be a buyer in the wings, such as the Nature-Springer conglomerate. I depend on this for my monthly literature updates, so I hope that the transfer will be seamless.

Normally you will not find anything on these pages dealing with politics, although in the aftermath of the Brexit decision in the UK it is hard to avoid. Like the majority of Scots, I voted to remain, although I have some sympathy with the alternative view. Scientists in particular have cause for concern because of uncertainty about access to EU funding, and I have doubts as to whether this will be resolved quickly. In my final years of employment at the James Hutton Institute, I had a share in three successive EU projects, which carried out some excellent science and allowed me to make some lasting international friendships. I was not cut out to organize such proposals, so I must pay tribute to the coordinator of these, Jean-Louis Sébédio of INRA, Clermont-Ferrand, France, for his dedicated professional work. The main projects lead to many publications, but the friendships formed enabled many other incidental and fruitful collaborations. It would be a great pity of scientists in the UK were no longer to contribute to international science in this way.

July 13th, 2016

Nowadays, I more interested in what lipids do in nature, i.e. their biological functions, than in other aspects of their chemistry and biochemistry. I have just found a paper describing what appears to be a completely new function for lipids. The swordfish can swim faster than any other living creature, and it is now reported that it may achieve its high speeds in part thanks to an organ that produces a wax from oil-excreting pores in the skin of the head. It is hypothesized that it "creates a super-hydrophobic layer that reduces streamwise friction drag and increases swimming efficiency" (Videler, J.J. et al. Lubricating the swordfish head. J. Exp. Biol., 219, 1953-1956 (2016); DOI). I have to wait six months until access is opened fully to the paper, but from the abstract the wax consists of methyl esters.

The essential fatty acids of the omega-6 and omega-3 families are "essential" because they cannot be synthesized de novo in animal tissues where they have innumerable functions, not least as precursors of the eicosanoid, docosanoids, and so forth. However, there are many other fatty acids that are not essential in this sense but for which there is an absolute requirement in animals. For want of a better term, I have been calling them "vital" fatty acids here and elsewhere. Those that fall into this category may be surprising to some of you as they are mainly saturated and monoenoic. For example, N-linked myristic acid is required to ensure 150 different proteins take their proper station in membranes in humans. Similarly, 500 proteins require S-acylated fatty acids, most of which is palmitic acid. The peptide hormone ghrelin has an absolute requirement for O-acyl linked octanoic acid to function. Oleic acid linked to ammonia is a hormone in the brain that induces sleep, while linked to ethanolamine it is produced to indicate satiety in the gut. Wnt proteins are central mediators of animal development, influencing cell proliferation, differentiation and migration - they are N-palmitoylated on a conserved cysteine residue and have a second unusual O-acyl modification with palmitoleic acid; the latter is essential to bind the protein to both a transporter and its receptor in cells. Multi-methyl-branched fatty acids, such as pristanic and phytanic acids, are reported to affect cellular metabolism through regulating gene expression. Arguably the most important of all is palmitic acid, which is the precursor of sphingoid bases and thence of all sphingolipids. There may be many more vital fatty acids that might be added to this list.

July 6th, 2016

In view of the commercial importance of seed oils for the human diet, most plant biochemists will be familiar with the biosynthesis and metabolism of triacylglycerols in seeds. However, until recently, little attention has been given to triacylglycerols in the vegetative tissue of plants. They are important for pollen function, but there has been little interest in the low amounts present in leaves and stems. This is changing in the era of genetic engineering as it is evident that increasing the energy level in green tissues through increasing the concentration of triacylglycerols would increase the energy available for nutritional purposes and for biomass production. A new review discusses what has been achieved and what may be possible (Xu, C.C. and Shanklin, J. Triacylglycerol metabolism, function, and accumulation in plant vegetative tissues. Annu. Rev. Plant Biol., 67, 179-206 (2016); DOI). As an example, the authors point out that increasing the oil content of sugar cane biomass to 1.5% could produce a similar oil yield per acre as canola.

It is always fascinating to read a paper describing a major new advance in lipid science, but sometimes a publication that may appear more prosaic can be of great value. Of course, it is always difficult to decide on first reading what may come into this category, but I suspect that one such will prove to be an invaluable compilation of data on retention properties of lipids in reversed-phase HPLC systems (Ovčačiková, M. et al. Retention behavior of lipids in reversed-phase ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry. J. Chromatogr. A, 1450, 76-85 (2016); DOI).

Incidentally, the ISI web of Science, which I used to compile my reference lists, omits the accents on letters in the names of scientists from European countries. When I become aware of them (as with the last), I try to insert them here, but inevitably I miss very many for which I apologize. One of the reasons I stopped working with AOCS on the web was that they insisted on moving from the international html standard to a proprietary US system, which made the introduction of accented letters and symbols of all kinds a tedious task that was fraught with errors.

Author: William W. Christie Updated: December 6th, 2017 Credits/disclaimer LipidWeb logo