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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 first few months) can be accessed here..

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.

June 29th, 2016

Scottish thistleThe journal Biochimie (Volume 125) contains a special issue section on the topic of 'Lipids, Signaling and Pathophysiology', guest edited by Professor Hugues Chap. The editor has contributed a fascinating autobiographical review describing his research career, and especially how he and his colleagues studied and used phospholipases to solve biochemical problems (Chap, H. Forty five years with membrane phospholipids, phospholipases and lipid mediators: A historical perspective. Biochimie, 125, 234-249 (2016); DOI). The early work explored phospholipid structure and metabolism in relation to membrane organization, followed by pioneering work on lysophosphatidic acid, the biochemistry of platelet-activating factor and the role of phosphoinositides in cell signaling. In recent years, novel digestive (phospho)lipases have been discovered and novel data on lipid mediators is promised. I was intrigued by his interaction with Jacques Beneviste, one of the discoverers of platelet-activating factor, who later published more controversial and irreproducible work.

There appears to be little doubt of the general health benefits of the omega-3 series of fatty acids, although there is no uniformity of opinion on some aspects. A new review discusses the availability of these fatty acids in a wide variety of natural ecosystems and the potential limitations for the food web, especially for human consumers (Twining, C.W. et al. Highly unsaturated fatty acids in nature: what we know and what we need to learn. Oikos, 125, 749-760 (2016); DOI). The paper is open access.

Formula of dioxolane A3 (DXA3)More than fifty years after the discovery of prostaglandins, new eicosanoid structures and classes continue to be found. The latest is 8-hydroxy-9,11-dioxolane eicosatrienoic acid (dioxolane A3, DXA3), which is a platelet-derived lipid generated by cyclooxygenase-1 that can activate or prime human neutrophils. It is characterized by a unique five-membered endoperoxide ring, and is presumed to have a role in innate immunity and acute inflammation (Hinz, H. et al. Human platelets utilize cycloxygenase-1 to generate dioxolane A3, a neutrophil-activating eicosanoid. J. Biol. Chem., 291, 13448-13464 (2016); DOI). The paper is open access.

June 22nd, 2016

Regular readers will know that I tend to avoid nutritional comment here, because present conclusions rarely seem to pass the test of time. However, some items seem to be worth a few words on occasion. Some years ago I found a few papers suggesting that omega-3 fatty acids were beneficial towards peridontal disease and I passed on the information to a friend who was troubled by gum disease. The data has now been reviewed in a new publication and while most studies appear to have small sample sizes, the early conclusions appear to be sound (Chee, B. et al. Omega-3 fatty acids as an adjunct for periodontal therapy-a review. Clin. Oral Invest., 20, 879-894 (2016); DOI). My friend is a group of one with no control for comparison but claims some success.

I had thought that the assertion of the European Food Safety Authority that arachidonic acid was not required in the infant diet when docosahexaenoic acid was present had been quashed years ago, but apparently not. Their assumption seems to be that as long as sufficient linoleic acid is available in the diet, there is no need for arachidonic. The failings in this argument have been pointed out by Professor Brenna before, and are repeated in a new publication (Brenna, J.T. Arachidonic acid needed in infant formula when docosahexaenoic acid is present. Nutr. Rev., 74, 329-336 (2016); DOI). All breastfed term infants of adequately nourished mothers consume both DHA and ARA, and I agree with the author that a very good reason indeed is needed before anyone can recommend deviation from the natural intakes. No attention appears to have been paid to vascular or immune function or to cognitive benefits.

June 15th, 2016

I have just been acquainting myself with ion mobility spectroscopy, which I have not encountered before in relation to lipid analysis and is a technique that separates ions from small molecules up to protein complexes based on their differential mobility through a buffer gas. Coupled with mass spectrometry, it acts as a tool to separate complex mixtures and resolve ions that may be indistinguishable by mass spectrometry alone with high sensitivity and a low signal to noise ratio. It came to my attention from a paper in an ACS publication, though because of the publisher's restricted access policy I have only been able to read the abstract (Sarbu, M. et al. Electrospray ionization ion mobility mass spectrometry of human brain gangliosides. Anal. Chem., 88, 5166-5178 (2016); DOI). In addition to confirming much of what is known of ganglioside composition in such a seemingly well-studied organ, the authors found several novel gangliosides including a remarkable series of mono- up to octasialylated molecules.

It has long been known that phosphatidylethanolamine reacts with glucose and other sugars to form first unstable Schiff bases, which then rearrange to produce Amadori products, especially under hyperglycemic conditions. These can undergo further reactions, for example with reactive oxygen species to form carboxymethyl- and carboxyethyl-adducts. There are brief notes on this web site here on this subject. However, I have to confess that to date I have not paid too much attention to the biological consequences of these reactions. It now appears that Amadori-phosphatidylethanolamine may be a useful predictive marker for hyperglycemia in the early stages of diabetes, and that the various products also have the potential to trigger pathological processes including the neuropathy and retinopathy associated with diabetic complications. They induce the production of pro-inflammatory cytokines and that they have a role in apoptotic cell signaling. Unsurprisingly, such changes to the phospholipid head group change the biophysical properties of membrane bilayers appreciably and can lead ultimately to the disintegration of cell membranes. A new publication on the topic has improved my perception of these biological consequences (Annibal, A. et al. Structural, biological and biophysical properties of glycated and glycoxidized phosphatidylethanolamines. Free Rad. Biol. Med., 95, 293-307 (2016); DOI).

June 8th, 2016

While I have been enjoying the sunshine of the Canary Islands over the last week, the world of lipids has continued to turn. A colleague has brought an article in the Guardian newspaper to my attention that discusses an EU proposal to make all scientific papers open access by 2020. To quote the article - "The changes are part of a broader set of recommendations in support of Open Science, a concept that also includes improved storage of and access to research data". Obviously this will change the economics of scientific publication substantially, and I can't see print copies of journals continuing for much longer - the increasing cost of postage alone will see to that. Personally, I find it frustrating that I can't access digital copies of my own early publications, which I would like to have simply for record purposes. In fairness, many publishers are making more articles, especially reviews, freely available nowadays, and for example I have obtained a number on line in recent weeks from the Nature Publishing Group, formerly a closed book.

A new publication from Serhan's laboratory shows that human milk possesses a suite of proresolving specialized proresolving mediators, including resolvins, protectins, maresins and lipoxins at bioactive levels (pico-nanomolar concentrations) (Arnardottir, H. et al. Human milk proresolving mediators stimulate resolution of acute inflammation. Mucosal Immunol., 9, 757-766 (2016); DOI). The authors demonstrate that these lipid constituents have beneficial effects in the resolution of inflammation and bacterial infection, and they suggest that they "educate the innate immune system in early life". The paper is open access.

I would be interested in learning whether such lipids are present in cow's milk and survive pasteurization, as this is a major component of the human diet through much of life.

The Journal of Bioenergetics and Biomembranes has a special issue (Volume 48, Issue 2, April 2016) devoted to the topic of "Essential Roles of Lipids in Mitochondrial Function and Pathology" (Issue Editor: Binks W. Wattenberg).

May 25th, 2016

Scottish thistleIn developing the Lipid Essentials section of this website, I believe that I have now included all the major lipid classes (please point out any omissions if I am wrong). The last piece of the jigsaw was a document dealing with bioactive aldehydes. I had put this topic off for years, partly because it did not really interest me but mainly because too much of the formation and biological activity appeared to be uncontrolled. On the other hand, I had included a section on the reaction of aldehydes with phosphatidylethanolamine some time ago, so I felt that I had to see if I could write something on the wider picture. In fact, once I got into it, the subject was much more interesting than I anticipated. True there are an incredible number of possible aldehyde products formed in cells, most of which don't do very much, while others simply add arbitrarily to form covalent bonds with what appear to be random proteins to inhibit their activities. At high concentrations, these are cytotoxic and can lead to cell death. On the other hand, some of the aldehydes, and especially 4-hydroxy-trans-2-nonenal derived from the n-6 family of polyunsaturated fatty acids is an endogenous activating ligand of peroxisome proliferator-activated receptor gamma (PPARγ) at low and noncytotoxic concentrations. It is believed to have beneficial effects in that it regulates genes that control the oxidative capacity of the mitochondrion, stimulates detoxification mechanisms and represses inflammation. My new web page is online, but I regard it as a work in progress that I must return to soon. This is one of the advantages of the web - changes can be made when new information comes to light or the author has second thoughts on any topic.

Formula of 4-hydroxy-trans-2-nonenal

In science, it can be dangerous to make too many assumptions. When a natural analogue of the long-chain base sphingosine was discovered that lacked the hydroxyl group in position 1, it was termed 'deoxysphingosine', and it was assumed that the double bond would be in position 4 and of the trans configuration as in sphingosine per se. Now, a study just accepted for the Journal of Lipid Research shows that the double bond is in position 14 and is of the cis configuration (Steiner, R. et al. Elucidating the chemical structure of native 1-deoxysphingosine. J. Lipid Res., DOI). It appears that an as yet unknown Δ14-desaturase is responsible.

May 18th, 2016

Arsenic-containing lipids ('arsenolipids') were first detected in marine samples in the 1970s, but there was no sustained interest until relatively recently when modern mass spectrometry methods greatly facilitated their detection and characterization. An additional stimulus to research is that the arseno-hydrocarbon are now known to be highly toxic. Initially, the arsinoyl-fatty acids were thought to be present only in unesterified (free) form, until they were detected in triacylglycerols of whiting. Now, a new study has found arsinoyl fatty acids in the phospholipids of fish roe, including a novel C30 fatty acid of this type with eight double bonds (Viczek, S.A. et al. Arsenic-containing phosphatidylcholines: a new group of arsenolipids discovered in herring caviar. Angew. Chem.-Int. Ed., 55, 5259-5262 (2016); DOI). It raises that possibility that these unusual lipids may have some as yet undefined metabolic role in fish.

The role of lipids as signalling molecules in plants is very different from that in animals. Phosphatidic acid is especially important in this connection in plants, but it seems that we know very little about any putative role for lysophosphatidic acid. Phosphoinositides are important signalling molecules in plants, but a very different group of molecular forms is involved from those in animals. On the other hand, diacylglycerols derived from phosphoinositides appear to have no signalling function in plants. Then there are the oxylipins, which are derived primarily from linolenic acid in plants as opposed to arachidonic acid in animals. A new review is available on this topic (Hou, Q.C. et al. Lipid signalling in plant responses to abiotic stress. Plant Cell Environ., 39, 1029-1048 (2016); DOI).

For those who have a subscription or are sufficiently patient to wait until access is opened, there is and interesting symposium - "More Signalling 2015: Cellular Functions of Phosphoinositides and Inositol Phosphates" in Biochemical Society Transactions

May 11th, 2016

The Journal of Lipid Research has the enlightened policy of putting accepted papers online in manuscript form ahead of publication. As I don't have direct access to the journal, it enables me to keep the pages here up-to-date, as well as satisfying my general interest in lipid science. Currently, a fascinating historical review is now available in this format (Martin, S.A. et al. The discovery and early structural studies of arachidonic acid. J. Lipid Res. DOI). Arachidonic acid was first discovered in 1907 and named in 1913, but in the absence of all the chromatographic and spectroscopic techniques we now take for granted, it was 1940 before the positions for the four double bonds was determined. The stereochemistry of these was confirmed by total synthesis in 1961. If this is of interest to you, I can also recommend an article by Frank Gunstone on "Fatty acid analysis before gas chromatography" in the AOCS Lipid Library.

In my days as a book and journal editor, it was very frustrating to find that in producing a review volume on a specific topic the publication date was decided by the slowest author, by which time the more prompt authors feared that their contributions might be already out of date. The Journal of Lipid Research has got around this problem by publishing review series over several months as papers become available, rather than as a single volume. The latest topic concerns lipoprotein(a) with the first papers now formally published and with others just appearing in final manuscript form. This is an LDL-like particle containing a specific highly polymorphic glycoprotein named apolipoprotein(a) (apo(a)), which is covalently bound via a disulfide bond to the apoprotein B100. There is a strong correlation between the concentration of this and cardiovascular disease, but from what I have read so far it appears that the mechanism for this effect is not at all clear. I imagine that I was not alone in being confused by the terminology apo(a) versus apo A, as the two have nothing in common. The reason is that apo(a) was characterized and named well before the apo A, B, C, etc. nomenclature was developed. The Introduction to the series is worth reading even if the topic is of marginal interest to you.

May 4th, 2016

I believe it is especially important to keep up-to-date with the literature on specialized pro-resolvin mediators (protectins, resolvins and maresins) as these metabolites of the (n-3) series of essential fatty acids are proving to have such important biological activities with considerable therapeutic potential. Each new publication from the laboratory of Professor Charles N. Serhan seems to have a fascinating new story to tell. Over the last two years, there has been the important discovery of sulfido-peptide conjugated mediators with some structural similarity to the cysteinyl-leukotrienes. Those derived from maresins were the first to be found but the 17-series protectins derived from docosahexaenoic acid were then shown to be produced by human leukocytes and were highly abundant in lymphatic tissue. Now, a new publication demonstrates that among many other related metabolites macrophages produce a protectin analogue PCTR1, via the intermediate 16S,17S-epoxy-protectin, which enhances resolution of bacterial infections (Ramon, S. et al. The protectin PCTR1 Is produced by human M2 macrophages and enhances resolution of infectious inflammation. Am. J. Pathol., 186, 962-973 (2016); DOI). The paper is open access.

Formula of protectin PCTR1

April 27th, 2016

Scottish thistleI have written extensively on most classes of lipids in the Lipid Essentials section of this website, but I consider myself as a populariser of lipid science and certainly not an expert in any one area. While I try to keep abreast of new research findings, I am dependent on the latest review articles by real experts to put new information into a proper perspective. Hence my frequent reference to new reviews in this blog. I run into problems where there are no relevant review articles and I have most difficulty with protein-containing lipids, such as lipoproteins and lipopeptides, which I suppose can be considered outwith the lipid mainstream. A new publication on the analysis of lipopeptides of cyanobacteria lead me to a number of interesting research publications, which I have tried to pull together some salient facts for these pages (Urajová, P. et al. A liquid chromatography-mass spectrometric method for the detection of cyclic β-amino fatty acid lipopeptides. J. Chromatogr. A, 1438, 76-83 (2016); DOI). I was most struck by the fact that many of these contained what were to me novel fatty acids with amine groups in position 3, together with hydroxyls in position 2, and often long saturated alkyl chains together with at least one C18 fatty acid with two groups of three conjugated double bonds. As many of the papers were written by protein chemists, these are often described as 'novel amino acids' not 'amine-containing fatty acids' so it is not surprising that they might be missed in my regular computerized searches.

Cutins and suberins are distinct layers on the surface of higher plants with similar but highly unusual lipid compositions (simplistically, suberins form the external layer or bark on woody plants). They contain complex polyesters of polyhydroxy, epoxy and dibasic acids, together with aromatic polymers and glycerol in suberins, compositions that are very different from those of any other living tissues. Recent reviews in open access journals have clarified the distinctions between the two layers for me (Fernández, V. et al. Cuticle structure in relation to chemical composition: re-assessing the prevailing model. Front. Plant Sci., 7, 427 (2016); DOI. Graça, J. Suberin: the biopolyester at the frontier of plants. Front. Chem., 3, 62 (2015); DOI).

April 20th, 2016

Did you know that when you cough, prostaglandins play a major part in the cough reflex? Prostaglandin PGE2 in particular mediates the action via a specific receptor, with a further involvement from PGD2. This is a minor but interesting fact from a new review, which I have been reading to update my web page on prostanoids here (Rumzhum, N.N. and Ammit, A.J. Cyclooxygenase 2: its regulation, role and impact in airway inflammation. Clin. Exp. Allergy, 46, 397-410 (2016); DOI).

It is now recognized that an enormous number of proteins are subjected to covalent lipid modifications of various kinds in order to target them to those membrane locations where they are required to carry out their specific functions. Various linkages are involved and often very specific fatty acids. For example, I have never been clear on how or why nature has selected myristic acid, which is such a minor component of tissues, for the irreversible N-acylation of proteins. This is especially puzzling in that this modification alone is not sufficient to hold the protein in a membrane and further S-palmitoylations are required for stable anchorage. This particular question is not answered in a substantial new review of the topic, but this does not hinder me from recommending it, especially as it is open access (Hentschel, A. et al. Protein lipid modifications - more than just a greasy ballast. Proteomics, 16, 759-782 (2016); DOI).

I have never been fond of the term 'hydrophilic interaction liquid chromatography or HILIC', or to be more accurate I don't like the way it is promoted as a new technique by manufacturers. Only the name is new as such columns have been in use for more than 30 years. Also, many analysts simply say they are using HILIC chromatography without specifying details of the column chemistry, which can often be difficult to find in the manufacturer's literature. I have no complaints, however, about a new publication that is quite clear about the chemistry of the columns the authors tried out for a particularly difficult lipid analytical problem (Cífková, E. et al. Hydrophilic interaction liquid chromatography-mass spectrometry of (lyso)phosphatidic acids, (lyso)phosphatidylserines and other lipid classes. J. Chromatogr. A, 1439, 65-73 (2016); DOI). The best separations were obtained with one new to me with a silicon hydride surface chemistry.

April 13th, 2016

It has long been evident that aberrations in innumerable aspects of lipid metabolism can have serious consequences for human diseases. However, it is also true that certain lipids have considerable pharmacological and therapeutic potential. Gangliosides are highly complex sphingolipids and their biochemistry is equally complex, although they tend to be neglected by main-stream lipid scientists because they are lost during extraction by most common extraction procedures in the aqueous 'waste'. Ganglioside GM1 is one of the simplest gangliosides and the easiest to obtain on a relatively large scale, and its chemical and biological properties are described in a new review (Aureli, M. et al. GM1 ganglioside: past studies and future potential. Mol. Neurobiol., 53, 1824-1842 (2016); DOI). In the 1990s, gangliosides were tested in various therapeutic situations with variable results. Eventually, trials were stopped because they appeared to show that some patients were developing antibodies that promoted peripheral neuropathies like the Guillain-Barré syndrome. Now, these results are being re-evaluated and new methods of ganglioside delivery are being developed in the hope of eliminating the potential problems.

A second lipid class with more immediate therapeutic potential is the nitro fatty acids, which have "revealed clinically relevant protection from inflammatory injury in a number of cardiovascular, renal and metabolic experimental models" according to a new review (Villacorta, L. et al. Nitro-fatty acids in cardiovascular regulation and diseases: characteristics and molecular mechanisms. Front. Biosci.-Landmark, 21, 873-889 (2016); DOI). Indeed, Phase II clinical trials are already underway in patients with chronic kidney diseases.

Incidentally, I do not have direct access to either of these publications, but received digital copies courtesy of the authors and ResearchGate. In my early career, I must have spent a very considerable sum on postage for reprint requests and in turn on reprints and postage to send to others. I hope that such new online systems do not make it too easy to forget to show our gratitude to authors.

April 6th, 2016

I have to confess that when I saw the first papers on the beneficial effects of conjugated linoleic acid (CLA) from Michael Pariza's lab in Wisconsin back in 1987 I was highly sceptical. In my defence, at that time it seemed a novel concept to find C18 fatty acids, especially those that were 'non-natural', with any kind of biological function, and I soon came round to a correct view. We now realize that many different fatty acids, including those that are saturated or with branched-chains or with only one double bond, can have profound effects on animal metabolism. Recent research suggests that many more conjugated fatty acids other than those derived from linoleate, including those produced from α-linolenic acid, nonadecadienoic acid and eicosapentaenoic acid by incubation with microorganisms, may have pharmacological value. For example, they have been found to have "anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties". These are discussed in a fascinating new review, which also points out how much is still to be learned of the mechanisms behind their actions (Hennessy, A.A. et al. Sources and bioactive properties of conjugated dietary fatty acids. Lipids, 51, 377-397 (2016); DOI).

My own first brush with CLA came more than 40 years ago in a short study of the phosphatidylcholine of sheep bile, which had been reported to contain high concentrations of α-linolenic acid. In fact, I showed that half of what was thought to be 18:3(n-3) was 9c,11t-18:2 with which it co-chromatographed on the packed GC columns then in use (Christie, W.W. The structure of bile phosphatidylcholines. Biochim. Biophys. Acta, 316, 204-211 (1973); DOI). This is still a unique phospholipid composition for a mammalian tissue, and I have never come up with a convincing biological explanation.

March 30th, 2016

Formula of 3-pyridylcarbinol tetradecanoate3-Pyridylcarbinol esters, formerly termed 'picolinyl esters' incorrectly, appear to have fallen out of favour for mass spectrometric identification of fatty acids in recent years. While they are arguably the best of the nitrogen-containing derivatives in mass spectrometric terms, their chromatographic properties are less desirable in that they require rather high GC column temperatures for separation, which often means that non-polar phases with poorer resolution may be needed. Also, the preparation procedures are tedious in comparison to the simple one-pot method used for DMOX derivatives, for example. A seemingly simple method involving base-catalysed transesterification with potassium tert-butoxide was described some years ago, but I have never obtained good yields with it - I suspect because it is difficult to remove traces of moisture from the reagents. Now two alternative transesterification methods for preparation of 3-pyridylcarbinol esters have appeared that look promising.

The first involves simply heating the fatty acid methyl esters with 3-pyridylcarbinol in the presence of a molecular sieve that acts both as a reaction catalyst and to sequester the methanol released. The reaction is carried out in toluene under reflux overnight so that minimal work-up conditions are required (Sieben, D. et al. Preparation of the even-numbered 3-oxo fatty acid nicotinyl esters from C6:0 to C18:0. Tetrahedron Letts., 57, 808-810 (2016); DOI). I have yet to get hold of the second paper, but according to the abstract it uses a commercial immobilized enzyme from Candida antartica in toluene at 50°C for 1 hour as transesterification catalyst to derivatize fatty acids in the form of triacylglycerols (Kim, C.S. et al. Lipase-catalyzed synthesis of fatty acid pyridylcarbinol ester for the analysis of seed lipids. J. Am. Oil Chem. Soc., 93, 339-346 (2016); DOI). I suspect that the latter would also work with methyl esters. As the real test of all new procedures is how well they work in other labs, I will look forward to seeing further publications on their use.

March 23rd, 2016

Scottish thistleA new publication poses an interesting question (Tsikas, D. Quantitative analysis of eicosanoids in biological samples by LC-MS/MS: Mission accomplished? J. Chromatogr. B, 1012, 211-214 (2016); DOI). In essence, the author is discussing the gradual replacement in the eicosanoid literature of GC-MS/MS techniques with LC-MS/MS. In his opinion, GC-MS methods have the advantage that the methodology has been established over nearly 40 years for what is an enormously challenging task to analyse metabolites in such low natural abundances. LC-MS obviously has great potential, but demands considerable knowledge of classical chemistry, so it is easy to over estimate the capabilities of the technique. While LC-MS no longer requires the use of derivatization techniques, Tsikas believes that this "is absolutely necessary for all eicosanoids". He also suggests that the desire to analyse as many different classes of compounds in a single analytical run is doomed to failure because of the need to make compromises that may favour one class of compounds over others, and he cites examples to prove his point.

I have never worked in this area myself, so my knowledge is entirely academic and I won't comment further. Nor do I need to as the journal editors have provided a rebuttal of many of the points raised in the following paper (Gachet, M.S. and Gertsch, J. Quantitative analysis of arachidonic acid, endocannabinoids, N-acylethanolamines and steroids in biological samples by LCMS/MS: Fit to purpose. J. Chromatogr. B, 1012, 215-221 (2016); DOI). I have simplified the debate here, and I encourage you to decide for yourself.

The journal Experimental Cell Research (Volume 340, Issue 2, Pages 171-328, January 2016) contains a special section on the topic of "The Biology of Lipid Droplets" (edited by Marlon Schneider).

March 16th, 2016

The new mass spectrometry procedures that have revolutionized the approach to lipid analysis have done more than just simplify the task. They have also changed the way we think about molecular species of each lipid class, as these are the primary data produced which have to be collated to obtain the amounts of lipid classes. One obvious problem is that so much data are produced that it is almost impossible to summarize it or present it in such as way that inter-laboratory comparisons are feasible. I certainly can't attempt it and I am grateful when other seek out salient points for me. A new review does just this and draws attention to a number of examples where single molecular species of particular lipids participate in biological processes while related molecules have no influence (Kimura, T. et al. Roles of specific lipid species in the cell and their molecular mechanism. Prog. Lipid Res., 62, 75-92 (2016); DOI). It is perhaps not surprising that arachidonic acid is so often involved.

One methodology that ought to be better known to lipid analysts is the use of 31P NMR for the identification of phospholipids. It enables identification and accurate quantification of total diacyl, alkylacyl and alkenylacyl forms of each phospholipid class. The data obtained are manageable and often sufficient for many biological purposes. A new automated approach to this methodology utilizes 1H chemical shifts for assignment and 31P intensities for quantification enabling "20 different lipids to be automatically and unambiguously assigned and quantified" (Balsgart, N.M. et al. High throughput identification and quantification of phospholipids in complex mixtures. Anal. Chem., 88, 2170-2176 (2016); DOI).

The open access journal Translational Cancer Research (Vol 4, No 5, October 2015) is largely devoted to the topic of "Lysophospholipids on Immunity and Cancer" (edited by Hsinyu Lee and Markus H. Gräler). As might be expected, many of the review articles are concerned with the biochemistry and function of sphingosine-1-phosphate. There appears to be no diminution in the interest in this fascinating lipid.

March 9th, 2016

A large part of the impetus for setting up a website when I reached retirement age at the Scottish Crop (or James Hutton) Research Institute was the realization that I was sitting on a wealth of mass spectrometry data, especially of various fatty acid derivatives, which could potentially be lost to the wider scientific community. Many journals do not allow full mass spectra to be published, restricting authors to a list of key ions; all journals restrict the number of mass spectra that can be illustrated in any publication. Similarly, most commercial libraries inevitably have a finite number of spectra available to them, and then they can only show a select number of the more abundant ions. A complete spectrum can be so much more meaningful.

One important feature that I have come to understand better with experience is that the general pattern or fingerprint of a spectrum can give useful information, even if it does not lead to a definitive identification or lend itself to a ready mechanistic explanation. For example, back in 1967 I published a paper on my post-doc work with Prof. Ralph Holman of the Hormel Institute in which I synthesised the methylene-interrupted C18 dienoic fatty acids from the 2,5-, 3,6,- through to the 14,17-isomer. Our conclusion on the mass spectra of the methyl ester derivatives was that only the first of these was different from the rest and interpretable in terms of the double bond positions. However, I have come to realize that in fact the 3,6-, 4,7- and 5,8-isomers each have distinct and consistent spectra, that differ in significant ways from that of methyl linoleate (see web page). I cannot explain these in mechanistic terms, but if analysts come across a spectrum of a C18 diene that differs in the pattern of ions from that of linoleate they should consider further work to establish the identity. Similarly, it is usually considered that the methyl esters of positional isomers of C18 monoenes all have identical spectra, other than that of 2-18:1. This not so, and in particular I recognized the distinctive fingerprint of 3-18:1 at first glance when I was presented with mass spectra from a new seed oil recently. In the Archive page, there are spectra of 11 different positional isomers of C18-trienes as the methyl esters - all with significantly different fingerprints, even if only a few of these are immediately interpretable in terms of double bond positions.

Incidentally, I was once approached by a commercial library who wished to buy my mass spectrometry files. After much debate I named a price, and was inadvertently sent an internal memo obviously not intended for me that stated that they would never get a cheaper price and to jump at the offer! However, I can assure you that I honoured my initial price - don't believe all you hear about thrifty Scots.

My first mass spectrometer was a small HP bench-top, and now I have access to a more recent Agilent/HP model of this type, though I was able to use other HP/Agilent models in between. While my first instrument had an HP computer attached with a 20Mb hard disk and its own proprietary operating system (then the most powerful computer in my Institute), HP/Agilent should be commended in that the file structure is still the same and my modern Windows system can read the 30 year-old files. Indeed, many of the spectra added over the last few years have come from a re-analysis of the old files, though many more have come from new samples or from old samples with alternative derivatization.

Back in 1999, I only had about a thousand spectra available, but now I have more than double this number on line, and I continue to add to them though more slowly nowadays. My hope is that my readers will continue to find these spectra and the attendant tutorials useful for some years to come. I have acknowledged many collaborators or those who have send me samples to add to the spectra on this website here... Also, I am always grateful for loans of HP/Agilent files that have enabled me to abstract spectra to add to those already online, and again I always acknowledge the source.

March 2nd, 2016

Following their discovery and structural characterization in the laboratory of H.E. Carter in the 1960s, glycosylinositol phosphoceramides (GIPCs) were the forgotten plant lipids for 40 years. It is only recently with the resurgence of interest in sphingolipids in general together with the development of modern mass spectrometry methods that their true importance has been realized. In studies with tobacco plants, it has now been demonstrated that a large part of the lipid component of the outer leaflet (apoplastic side) of the plasma membrane comprises bulky GIPCs together with sterols (free and glycosylated), while the inner leaflet (cytoplasmic side) contains digalactosyldiacylglycerols, phosphatidylserine and phosphatidylinositol-4,5-bisphosphate, amongst other lipids (Cacas, J.L. and 19 others. Revisiting plant plasma membrane lipids in tobacco: a focus on sphingolipids. Plant Physiol., 170, 367-384 (2016); DOI). Raft-like microdomains are believed to exist in both leaflets. The high concentration of GIPCs in the apoplastic leaflet is presumed to present a physical barrier involved in the maintenance of thermal tolerance, cell integrity and the responses to pathogens.

It has become evident in recent years that nitro fatty acids have important signalling functions in animal tissues, especially as anti-inflammatory agents. A new publication (open access) now suggests that they also have signalling functions in plants with nitro-linolenic acid being the key metabolite (Mata-Pérez, C. et al. Nitro-fatty acids in plant signaling: nitro-linolenic acid induces the molecular chaperone network in Arabidopsis. Plant Physiol., 170, 686-701 (2016); DOI)). There seems to be a single isomer in vivo as only a single peak is seen on GC analysis, but the precise structure does not appear to have been determined. It is involved in plant defence responses against different abiotic-stress conditions, mainly by inducing heat shock proteins. For example, it reacts to oxidative stress conditions by inducing high levels of ascorbate peroxidase. Its concentration rose also in response to wounding or exposure to salinity, cadmium, and low temperature. I have still to get hold of a new review relating nitro fatty acids to human disease conditions (Villacorta, L. et al. Nitro-fatty acids in cardiovascular regulation and diseases: characteristics and molecular mechanisms. Front. Biosci.-Landmark, 21, 873-889 (2016); DOI).

Following my notes on furanoid fatty acids in my last blog, a short review of their occurrence and function in plants has just appeared (Mawlong, I. et al. Furan fatty acids: their role in plant systems. Phytochem. Rev., 15, 121-127 (2016); DOI). The only function suggested is that they act as antioxidants, although I would still put my money on some as yet undefined signalling mechanism.

For those who have access, the latest issue of the journal Current Opinion in Clinical Nutrition and Metabolic Care (Vol 19, Issue 2) has a number of review articles on the theme of "Lipid Metabolism and Therapy" (edited by Philip C. Calder and Richard J. Deckelbaum).

Older entries in this blog are archived for at least a year here..

Author: William W. Christie Updated: August 2nd, 2017 Credits/disclaimer LipidWeb logo