The LipidWeb blank

Lipid Matters - A Personal Blog



Or "Lipids Matter". An occasional series of notes on publications or other items dealing with lipid science that seem to be of particular interest to the originator of this web page, Bill Christie. Inevitably, the selection is highly personal and subjective. Older entries are archived in separate web pages by year (see the foot of this page).


August 15th, 2018

Scottish thistleAlthough the immune system is essential to protect the body from infection, some immune responses can harm tissues. The eye is especially sensitive to immune reactivity, and it has now been determined that cholesterol sulfate is a key protective factor (Sakurai, T. et al. Cholesterol sulfate is a DOCK2 inhibitor that mediates tissue-specific immune evasion in the eye. Science Sign., 11, eaao4874 (2018);  DOI). This is produced by the Harderian gland, which secretes the lipids that form a protective layer in the tear film that covers the eye. Experiments with mice in vitro demonstrated that cholesterol sulfate selectively inhibits the guanine nucleotide exchange factor DOCK2 and by this means suppresses the migration of neutrophils and T cells. When the sulfotransferases responsible for the synthesis of this lipid were inhibited, inflammation occurred that could be cured by administering eye drops containing cholesterol sulfate. As it is produced by most animal cells and circulates in plasma, it seems to me that the next important question is whether cholesterol sulfate might be an endogenous factor that suppresses the immune system in other circumstances, and possibly in a less benign manner in tumours, for example.

The journal Nitric Oxide continues its series of review articles on the chemistry and biochemistry of the potent anti-inflammatory nitro fatty acids in volumes 78 and 79. A separate publication describes the anticancer effects of nitro fatty acids and proposes a mechanism (Kühn, B. et al. Anti-inflammatory nitro-fatty acids suppress tumor growth by triggering mitochondrial dysfunction and activation of the intrinsic apoptotic pathway in colorectal cancer cells. Biochem. Pharm., 155, 48-60 (2018);  DOI). The authors suggest that "these naturally occurring lipid mediators are a new class of well tolerated chemotherapeutic drug candidates for treatment of colorectal cancer or potentially other inflammation-driven cancer types." Good news indeed!

I am always interested in lipid oddities, and it is hard to think of anything more unusual than a triacylglycerol with acetate in position sn-2, as in the seed oils from Polygala species. This was first reported briefly in 1977 but has now been confirmed by mass spectrometry (Smith, M.A. et al. 2-Acetyl-1,3-diacyl-sn-glycerols with unusual acyl composition in seed oils of the genus Polygala. Eur. J. Lipid Sci. Technol., 120, 1800069 (2018);  DOI). Curiosity aside, if any species from the genus can be developed as a commercial crop, the oil may have potential as a low-viscosity biofuel/lubricant or reduced calorie food ingredient.

August 8th, 2018

The uncontrolled inflammatory response that is seen in sepsis is now recognized to be a major cause of death in the UK and I am sure elsewhere. One of the best hopes for novel therapeutic responses lies with the specialized pro-resolving mediators - resolvins, protectins and maresins, but how are such highly stereospecific structures to be produced on a scale that permits clinical testing? A new total synthesis of resolvin D4 (RvD4), which has three chiral hydroxyl groups and three cis- and three trans-double bonds, has just been published that has the potential to be developed on a commercial scale (Winkler, J.W. et al. Structural insights into Resolvin D4 actions and further metabolites via a new total organic synthesis and validation. J. Leukocyte Biol., 103, 995-1010 (2018);  DOI). The product was tested successfully against ischemia models in mice, and in so-doing the importance of the correct stereochemistry was emphasized. An editorial in the same issue of the journal provides a further perspective on the topic.

Resolvin D4

Every Saturday morning, I scan rapidly through the titles of around 500 publications dealing with lipid science to pick out a relative few that are useful to me for my web endeavours, and which are subsequently listed in my Literature survey pages. Inevitably, I miss many that are not picked out by the algorithm I use, or whose significance I do not recognize at first glance. One that I greatly regret missing when it first appeared deals with how lipids are distributed in membranes (Murate, M. and Kobayashi, T. Revisiting transbilayer distribution of lipids in the plasma membrane. Chem. Phys. Lipids, 194, 58-71 (2016);  DOI). I am now using it to update my web pages. When I was a young scientist, the work of van Deenen and colleagues in the Netherlands in which specific lipases were used to determine the sidedness of membranes attracted great interest. However, by today's standards, these methods seem relatively crude and new procedures involving immunoelectron microscopy are providing much greater selectivity and precision. Perhaps surprisingly, the one lipid for which we still lack reliable data is cholesterol, and it seems that new cholesterol-specific probes are required before it will be possible to reliably determine its transbilayer distribution.

August 1st, 2018

I have belatedly come across two fascinating and important papers on the subject of 12,13-dihydroxy-9Z-octadecenoic acid or 12,13-diHOME. This is a further example of a fatty acid with important biological functions that is not an eicosanoid or a docosanoid but an octadecanoid, derived in this instance from linoleic acid via the action of a CYP epoxygenase followed by an epoxide hydrolase. Last year, this was reported to promote fatty acid transport into brown adipose tissue during cold exposure, while the more recent publication suggests that it is a "novel exercise-stimulated circulating factor that may contribute to the metabolic changes that occur with physical exercise" both in humans and laboratory animals (Stanford, K.I. et al. 12,13-diHOME: an exercise-induced lipokine that increases skeletal muscle fatty acid uptake. Cell Metabolism, 27, 1111-1120.e3 (2018);  DOI). While these effects seem beneficial, there are earlier reports of adverse properties, for example that such oxidized linoleate metabolites may be atherogenic through the induction of pro-inflammatory cytokines and by formation of foam cells from macrophages by PPAR activation. Life is complicated!

Excuse a moment of pedantry, but I have often complained about the excessive use of abbreviations in publications, and the reason I missed these articles in my weekly searches was because of the use of the abbreviated name of the lipid in the title; this was not recognized by the search algorithm I use. The authors did use the word "lipokine" in the title and I could add this to my search algorithm, but a quick search in the Web of Science suggests that this term has only been used 14 times in the last five years and then mainly for palmitoleic acid for which it was originally coined. Should it be used more?

July 25th, 2018

Scottish thistleWhile animals have eicosanoids and docosanoids and plants have jasmonates and other oxylipins as lipid mediators of innumerable biological reactions, nematodes, including a number of human parasites, have ascarosides. These are glycolipids that consist of the mono-saccharide α-L-3,6-dideoxymannose or ascarylose, which occurs in few other organisms, linked glycosidically to the hydroxyl group of a 2-hydroxy alcohol or of an (ω-1)-hydroxy fatty acid. The nature of the alkyl moiety can vary appreciably and the free hydroxyl and carboxyl groups can be derivatized in various ways. For example, more than 200 ascarosides have been characterized from the model nematode species Caenorhabditis elegans with presumably many different functions.

Formulae of two representative ascarosides

Some of these are structural and provide an impermeability to the shell that protects eggs of certain nematode species from the harsh conditions in the intestines of host animals. Others function as pheromones as well as signalling molecules that regulate development and behaviour. For example, they control the entry and exit of nematodes from a dormant or 'dauer' stage. A new review (open access) describes the properties of these fascinating molecules (von Reuss, S.H. Exploring modular glycolipids involved in nematode chemical communication. Chimia, 72, 297-303 (2018);  DOI).

In my blog last week, I cited a review claiming benefits towards heart disease from eating fish (and presumably their fish oils), and since then two other reviews have appeared one claiming no such benefits and the other the opposite including increased longevity. Is it any wonder that I am confused by nutritional advice, even though the Fats of Life newsletter does its best to enlighten me. Of course fish oils have the potential to help with many more inflammatory conditions other than heart disease. Whether or not it will give me any health benefit, I will enjoy my smoked salmon sandwich at lunchtime.

July 18th, 2018

In my notes on proteolipids in the LipidWeb, I had quoted from a paper suggesting that there were approximately 300 myristoylated proteins in humans and a similar number in Arabidopsis. This figure has now been revised to more than 600 in each (Castrec, B. et al. Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern. Nature Chem. Biol., 14, 671-679 (2018);  DOI). The results came after the crystal structure of the N-myristoyltransferase-1 was determined. This showed that the enzyme has a characteristic binding cleft that is involved in the recognition of potential substrates for myristoylation (with some overlap with targets for N-acetylation); it also revealed potential sites for further S-palmitoylation, allowing recognition of sequences exhibiting both acylations.

I tend to pay little heed to dietary recommendations in terms of fats and oils as opinions seem to change with the seasons. On the other hand, when the American Heart Association publishes its recommendations, I feel that I must take note at least (Rimm, E.B. et al. Seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease: a science advisory from the American Heart Association. Circulation, 138, E35-E47 (2018);  DOI - open access). The last line of the abstract succinctly states the AHA position with which I can happily live - "We conclude that 1 to 2 seafood meals per week be included to reduce the risk of congestive heart failure, coronary heart disease, ischemic stroke, and sudden cardiac death, especially when seafood replaces the intake of less healthy foods." Following dietary recommendations that appeal to your taste buds may not be the best policy, but I am sure there are worse.

Aficionados of sphingolipids in general and gangliosides in particular will no doubt appreciate a new book on the topic (Ronald L. Schnaar and Pablo H.H. Lopez (editors) Gangliosides In Health And Disease. Progress in Molecular Biology and Translational Science, Volume 156, Pages 1-462 (2018) available from Science Direct). I have not seen it myself.

July 11th, 2018

It has become commonplace to see new reports of the biochemistry of oxylipins derived from the C20 and C22 polyunsaturated fatty acids, and it is easy to forget that there are some important metabolites of the more simple C18 fatty acids. In particular, I am thinking of the nitro fatty acids derived from oleate and linoleate, which have attracted increasing interest since the turn of the century. It seems that the story starts with the discovery in the 1990s that NO inhibited the oxidation of membranes and plasma lipoproteins more potently than α-tocopherol and in general had anti-inflammatory, antioxidant and tissue-protective effects. Subsequently, it became apparent that nitro fatty acids had a role in mediating these reactions largely because the nitro-alkene moiety has potent electron-withdrawing properties that favour reversible nitroalkylation reactions (Michael reaction) with proteins. A new brief review provides a fascinating introduction to the subject (Freeman, B.A. et al. The discovery of nitro-fatty acids as products of metabolic and inflammatory reactions and mediators of adaptive cell signaling. Nitric Oxide Biol. Chem., 77, 106-111 (2018);  DOI). The next issue/volume of this journal has a number of review articles on this general topic.

I tend to stay clear of medical and nutritional matters and leave the debate to those better qualified than I in these subjects. Nonetheless, I enjoy reading a provocative article from time to time such as the following, which is open access (Tsoupras, A. et al. Inflammation, not cholesterol, is a cause of chronic disease. Nutrients, 10, 604 (2018);  DOI). The authors suggest that cholesterol has been demonized but that platelet-activating factor, i.e. 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine or PAF, is the true culprit (apart from its main thesis, the paper is a comprehensive review of PAF activities). While I do not feel qualified to endorse the proposal, I have often wondered if the concentration on cholesterol by clinical scientists is in part due to its ease of analysis as one of the most abundant metabolites in molar terms in plasma (only surpassed by glucose). In contrast, PAF occurs in cells and exerts its effects at concentrations as low as 10-14M, and its analysis is technically daunting. It seems that we may need to employ more lipid analysts skilled in advanced mass spectrometry in future clinical studies.

An analytical development that has truly astonished me is the use of a special knife during surgery for ovarian cancer that enables differentiation of cancerous from borderline tumours in real time from differences in their lipid components by analysing aerosolized tissue by a mass spectrometric technique during electrosurgical dissection (Phelps, D.L. et al. The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS). Brit. J. Cancer, 118, 1349-1358 (2018);  DOI). The publication is open access.

July 4th, 2018

The hedgehog proteolipids are fascinating molecules, not least because they require both palmitate and cholesterol in covalent linkage for their essential functions, for example in limb development. Within the cell, they are produced in the endoplasmic reticulum and Golgi but then must be transferred to the exterior leaflet of the plasma membrane. From there, the fully lipidated proteins must travel a distance as much as 15 cell diameters until they encounter their signalling receptors, but exactly how this is accomplished has yet to be determined. Several proteins that are involved in extraction from the membrane and subsequent transport have been characterized, and at least three model systems for this transport have been proposed, although it appears that none is entirely satisfactory. A new review (open access) discusses the alternatives (Manikowski, D. et al. Taking the Occam's razor approach to hedgehog lipidation and its role in development. J. Dev. Biol., 6, 3 (2018);  DOI).

It often surprises me how relatively small changes in enzyme structure can alter the nature of their products, e.g. to switch between desaturation and hydroxylation. Animal tissues contain six ceramide synthases with very different specificities for fatty acid substrates and different tissue locations, and they appear to produce distinct molecular species of ceramides for particular functions. They are membrane bound enzymes with six membrane spanning regions. Now, they have been shown to differ primarily in only an 11-residue sequence in a loop between the last two putative transmembrane domains (Tidhar, R. et al. Eleven residues determine the acyl chain specificity of ceramide synthases. J. Biol. Chem., 293, 9912-9921 (2018);  DOI). As an editors' choice, the paper is open access.

Incidentally, the authors cite the LIPID MAPS® Lipidomics Gateway to the effect that ~40,000 different lipids have been identified to date, ~4000 of which are sphingolipids. I suspect that in the long term many more will be added to the totals, especially as more lipidomic analyses of plant lipids are undertaken. Whatever the true figure, I am sure that lipid scientists are going to be gainfully employed for many years to come - and I am looking forward to recording and celebrating their efforts.

June 27th, 2018

Scottish thistleI encounter publications dealing with new lipidomics studies of animal tissues in all my weekly literature searches, and as these often contain comparisons with human different disease states, it is important to take note of them. On the other hand, lipidomics studies of plants appear relatively infrequently, although it is vital that we understand what keeps plants healthy, especially when phosphate is limiting or when they are under salt stress. In the long term, this knowledge may also be essential to human health and nutrition. Analysis is daunting technically, as in addition to the common phospholipid classes, plants contain a wide range of distinctive lipids not encountered in animals. These include many different classes of glycosylmono- and diacylglycerols, glycosylinositol phosphoceramides and several sterols and sterol glycosides. This complexity is apparent in a new study in which 600 lipid species from 23 lipid classes were identified from a barley root extracts. These included 142 species of glycosyl inositol phosphorylceramides alone (Yu, D.Y. et al. A high-resolution HPLC-QqTOF platform using parallel reaction monitoring for in-depth lipid discovery and rapid profiling. Anal. Chim. Acta, 1026, 87-100 (2018);  DOI).

For similar reasons, it is important that we understand the biosynthesis, metabolism, and action of plant oxylipins, especially the jasmonates, which are so essential to the development of healthy plants as well as their response to stresses, and I can recommend a new review that gives a comprehensive account of this topic (Wasternack, C. and Feussner, I. The oxylipin pathways: biochemistry and function. Annu. Rev. Plant Biol., 69, 363-386 (2018);  DOI).

I have never paid any attention to Twitter, as I had conceived the idea that it was simply a vanity platform for would-be celebrities or a font for trivia. Now, I have had to reconsider this view as the virtues of the Twitter link on the LIPID MAPS® website have been pointed out to me. I have not had the courage to send a tweet myself yet, but you never know. Incidentally, the LIPID MAPS® Lipidomics Gateway has had a substantial revamp and is certainly much more eye-catching.

June 20th, 2018

An interesting review publication suggests that long-chain polyunsaturated fatty acids, as opposed to linoleic and linolenic acids, are the true essential fatty acids (Anez-Bustillos, L. et al. Redefining essential fatty acids in the era of novel intravenous lipid emulsions. Clin. Nutr., 37, 784-789 (2018);  DOI). Mice fed arachidonic and docosahexaenoic acids exclusively for five generations grew and reproduced normally, and these fatty acids are certainly vital for eicosanoid and docosanoid production and for innumerable other purposes when esterified to lipids in tissues. There is no doubt that we must have adequate amounts to ensure health. On the other hand, linoleic acid is required for skin ceramides and cardiolipin in heart mitochondria, for example. If the skin barrier integrity and energy production were less than optimal (if adequate for life) in the experimental animals, would this have been noticed? The authors suggest that linoleate could be supplied for other functions by retro-conversion of arachidonic acid, but this seems to me a circular argument - linoleate produces arachidonate produces linoleate - the chicken versus the egg. The debate is important in that alternative injectable lipid emulsions low in the C18 precursors are apparently being considered for clinical use. It seems to me that a sensible compromise would be to ensure that there are adequate amounts of all fatty acids that may have essential functions in any artificial feeding regime.

In my last blog, I urged other senior lipid experts to consider keeping active in or near retirement by writing for the web. My web career was initiated by a desire to see that the large repository of mass spectrometric information (electron impact) on fatty acids and other simple lipids, which I had accumulated, was preserved. There are now more than 2,100 spectra available in the LipidWeb. On the other hand, my former colleagues recently asked me to advise on an analytical problem involving plant sterols. As I did not have access to the Wiley Library and had only a few representative spectra of my own, this proved to be a time-consuming and rather tedious task to search the literature. Is there anyone out there who would consider producing a website akin to mine dealing with electron-impact mass spectra of sterols and their derivatives? You would do the lipid community a great service. Again, I would be happy to advise.

Although we are probably stuck with it, I don't particularly like the term "endocannabinoid", as to use yet another cliché - it is putting the cart before the horse. For example, anandamide does not mimic cannabinol, but rather cannabinol mimics anandamide. Whatever we call them, there is no doubt that endocannabinoids have profound biological effects in humans, and drugs that influence their metabolism are undergoing clinical trials. Therefore, it would not be surprising if cannabinoids per se have medicinal properties, although there is currently some controversy in the UK about such applications. It in no way endorses the use of cannabis for recreational purposes if we accept that drugs derived from it may have a legitimate place in pharmacopoeias. Few politicians appear to understand the difference between the two.

June 13th, 2018

Thioxo-arseno lipidI enjoy eating fish, and I am not going to be deterred by the findings that the arseno-hydrocarbons, which they contain albeit at very low levels, are highly toxic. From experiments with human cell lines in vitro, a new publication reports that arsenic-containing hydrocarbons influence gene expression and DNA methylation with the nature and magnitude of the effects dependent on the chain-length of the hydrocarbon (Müller, S.M. et al. Arsenic-containing hydrocarbons: effects on gene expression, epigenetics, and biotransformation in HepG2 cells. Arch. Toxicol., 92, 1751-1765 (2018);  DOI). One surprise was that high proportions of the starting compounds were transformed into thioxo analogues, i.e. with the oxygen atom replaced by sulfur, with trace levels as arseno-fatty acids and alcohols. Thioxo-arseno lipids might be expected to be more lipophilic than the parent compounds, but it is not yet known whether this transformation results in an increase in toxicity.

When I have what my wife calls "a senior moment", it seems that the fault may lie with my lipids and in particular my leukotrienes. Experiments with mice engineered genetically to have excess tau proteins, the second-most important lesion in the brain in patients with Alzheimer's disease, showed that they developed learning and memory problems as they aged. However, the effects were reversed by a drug that inhibits leukotriene formation by blocking the 5-lipoxygenase enzyme. There is a popular account of the work in Science Daily.

One of the main virtues of writing for the web is its immediacy. Not only do you see the results of your efforts at once, but you also have the opportunities to update anything you write whenever new information becomes available. For example, the figures and comments in this and last weeks' blogs were prepared not for the blog per se but initially for the essays on the appropriate topics in the Lipid Essentials section of this website. I make changes to one or other of these web pages nearly every day - sometimes simply to add or replace a reference and occasionally I regret to say to correct an error. Sometimes, I merely find a better way of explaining a point. If I had intended to use these figures in a review on one of these topics for a print publication, it might be a year before it appeared in a journal - not the same day - and then there would be no opportunities for correction or updating. There are hundreds of senior scientists out there with a wealth of knowledge on lipid science who I am sure would find some fulfillment by setting up their own web sites and writing for the web. It is so easy to do - why not give it a go? I will be happy to offer advice to anyone who wants to try.

June 6th, 2018

Plasmalogen catabolismI have been enjoying the sunshine of Gran Canaria for the last week, and lipid science has not been at the forefront of my thoughts. However, it took only a preliminary look at the literature on my return, to see that I had missed an important paper. The mechanism for the cleavage of the vinyl ether bond in plasmalogens has now been revealed as the result of a master class in elegant mass spectrometric experiments involving the use of stable isotopes (Jenkins, C.M. et al. Cytochrome c is an oxidative stress–activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage J. Biol. Chem., 293, 8693-8709 (2018);  DOI - open access as an editors' pick, as is an additional useful commentary by Howard Goldfine). Perhaps surprisingly, the key enzyme is cytochrome c, best known for its role in the respiratory chain of mitochondria. This must first be activated to produce peroxidase activity by an interaction with cardiolipin. After a complex series of reactions, the products are a lysophospholipid and an α-hydroxyaldehyde. The carbonyl oxygen is derived from water while that of the α-hydroxyl group comes from molecular oxygen (or possibly from oxidized cardiolipin). As the resulting lysophospholipid is usually enriched in arachidonic acid, this may have interesting implications for eicosanoid production. The findings are also relevant to Alzheimer's disease, as it has long been known that α-hydroxyaldehydes accumulate in the brains of affected patients.

Incidentally, a further new publication is relevant to the suggestion that oxidized cardiolipin may be involved in the reaction (Vähäheikkilä, M. et al. How cardiolipin peroxidation alters the properties of the inner mitochondrial membrane? Chem. Phys. Lipids, 214, 15-23 (2018);  DOI).

May 23rd, 2018

Scottish thistleIt is very rare to see a statue raised to commemorate a scientist, but I was pleased to see that Stephen Hawking was honoured at his death by being interred in Westminster Abbey. I only know of one lipid scientist who has been commemorated by a statue, and that is the great French chemist Michel Chevreul of whom there is a bronze statue in the Jardin des Plantes d'Angers in Paris. Of course that great stalwart of lipid research, the laboratory mouse, is commemorated by a bronze statue in a park in front of the Institute of Cytology and Genetics of the Russian Academy of Sciences in the city of Novosibirsk in Siberia, Russia. He/she is depicted knitting DNA (see the Wikipedia entry). In the main city square here in Dundee, we have a statue of Desperate Dan, a character from children's comics and a superhero of my own childhood. Our priorities must be different.

A candidate for the most unusual new lipid of the year is 1-phosphatidyl-2-acyl-glycero-3-phosphoethanolamine from a Gram-negative bacterial species; the structure has been tentatively identified by tandem mass spectrometric analysis (Luo, Y. et al. Nutrient depletion-induced production of tri-acylated glycerophospholipids in Acinetobacter radioresistens. Sci. Rep., 8, 7470 (2018);  DOI - open access). It is produced together with cardiolipin and lysocardiolipin, presumably from a common intermediate, only in the stationary phase of growth of the organism.

Structure of 1-phosphatidyl-2-acyl-glycero-3-phosphoethanolamine

Issue 8 (Volume 592, April 2018) of FEBS Letters contains a number of review articles on the theme of "Focus on… Yeast Lipid Biochemistry", all of which are open access.

May 16th, 2018

α-D-Galactosylceramides, i.e. cerebrosides with an α-D- rather than the usual β-D-linkage between galactose and ceramide, are present in trace amounts only in human tissues but they have profound biological effects. For example, studies with animal models have suggested that treatment with α-D-galactosylceramides may be effective against lung and colorectal cancers, melanomas and leukemia. Now, a phase I trial with high-risk melanoma patients has given promising preliminary results (Gasser, O. and 19 others. A phase I vaccination study with dendritic cells loaded with NY-ESO-1 and α-galactosylceramide: induction of polyfunctional T cells in high-risk melanoma patients. Cancer Immunology, Immunotherapy, 67, 285-298 (2018);  DOI). It is always pleasing to see that the potential of lipids in therapy is being realized. Unfortunately, not all glycosphingolipids are beneficial and a new short review of the influence of glycosphingolipids on cancer has been published (Zhuo, D.H. et al. Biological roles of aberrantly expressed glycosphingolipids and related enzymes in human cancer development and progression. Front. Physiol., 9, 466 (2018);  DOI - open access).

The bargain of the week is an open access review of triacylglycerol metabolism (Alves-Bezerra, M. and Cohen, D.E. Triglyceride metabolism in the liver. Comprehensive Physiology, 8, 1-22 (2018);  DOI). There are nearly 300 references, it is very well illustrated and it should be especially useful for teaching purposes. My only caveat is the use of the term 'triglyceride' instead of 'triacylglycerol', which has been recommended by IUPAC-IUB for more than 50 years. Two generations of biochemists have been taught the recommended nomenclature, so I am surprised to find the old used here. At least the authors did not use the hybrid term 'triacylglycerides', which I find much too often in the lipid literature. Am I being pedantic?

May 9th, 2018

In my blog of March 14th, I discussed a paper describing the synthesis of linoleic acid in primitive invertebrates, including insects, nematodes and snails. Hot on its heels, a new paper has just been published demonstrating that a large number of aquatic invertebrates possess the gene for a Δ15-desaturase and so can synthesise α-linolenic acid and polyunsaturated fatty acids of the omega-3 family (Kabeya, N. et al. Genes for de novo biosynthesis of omega-3 polyunsaturated fatty acids are widespread in animals. Science Advances, 4, eaar684902 (2018);  DOI - open access). It was pleasing to see that some of the authors were from the University of Stirling in Scotland. Until now, it had been believed that microorganisms were the main producers of polyunsaturated fatty acids of omega-3 fatty acids in the marine food web, but now it appears that animal species may make a significant contribution. In addition to adding the new information, I have had to make a small but important change to my web page on polyunsaturated fatty acids, by changing phrases such as "animals cannot produce essential fatty acids" to "higher animals cannot, etc".

It is 40 years since, the discovery of glycosylphosphatidylinositol (GPI)-anchored proteins, and thirty since the first complete structure was determined for the parasitic organism Trypanosoma brucei, and it since then it has become evident how important these are for so many aspects of metabolism in Eukaryotes. In their functional site on the outer leaflet of the plasma membrane, the flexible carbohydrate linkage provides GPI-proteins with a much higher degree of rotational freedom than is available to most other membrane proteins, facilitating their functions as signal receptors and host-recognition molecules. They have essential functions in the interaction of cells with their external environment by enabling the receipt of signals and the response to challenges as well as mediating adhesion of extracellular compounds to the cell surface. In parasitic protozoa, yeasts and fungi, GPI-proteins also participate in the structural integrity of the cell wall and with other complex glycans provide a layer of protection to the organisms. A new review is a valuable guide to the latter (Komath, S.S. et al. Generating anchors only to lose them: the unusual story of glycosylphosphatidylinositol anchor biosynthesis and remodeling in yeast and fungi. IUBMB Life, 70, 355-383 (2018);  DOI).

May 2nd, 2018

There has been no shortage of publications dealing with the molecular species of mitochondrial cardiolipin in recent years, but a new publication suggests that most of them suffer from a flaw in that they do not allow sufficiently for overlap with isobaric species (Oemer, G. et al. Molecular structural diversity of mitochondrial cardiolipins. Proc. Natl. Acad. Sci. USA, 115, 4158-4163 (2018);  DOI). I have been too long from the bench to fully comprehend the arguments, but the authors use a combination of HPLC-mass spectral data and a mathematical structural modeling approach to overcome the problems. The data are presented elegantly in graphical form for many different organisms and tissues, but I wish the authors had used the opportunities offered by having appendices to tabulate data at least for the major species, as they have done for fatty acid compositions. I would love to be able to list tabulated data from a modern paper in my web page on this lipid class to replace that from a 25 year old publication.

Do we now fully comprehend the structures of natural cardiolipins? Unfortunately, the answer is no because we know little or nothing about the positional distributions of fatty acids in the molecule. Cardiolipin has two chiral centres, one in each outer glycerol group, and this means that the four positions to which fatty acids are esterified are each metabolically distinct and can have different fatty acid compositions. As far as I am aware, no one has attempted to tackle the problem, which is unlikely to be solved by mass spectrometry. Analysts may have to resurrect enzymatic hydrolysis methods, which are stereo-selective but have been sadly neglected.

An interesting new paper (though I have only seen the abstract) suggests a close relationship between plasmalogen and cardiolipin biosynthesis (Kimura, T. et al. Substantial decrease in plasmalogen in the heart associated with tafazzin deficiency. Biochemistry, 57, 2162-2175 (2018);  DOI)). The authors establish that plasmenylcholine, which is abundant in linoleoyl species in heart mitochondria, is a substrate for tafazzin and may be important for the remodelling of cardiolipin. This may be especially relevant to the debilitating genetic disease Barth syndrome.

April 25th, 2018

Scottish thistleNew biological functions for lipids and new lipids per se continue to be found, and I have just caught up on one concerning the model nematode Caenorhabditis elegans. This contains a novel glucosylceramide with phosphoethanolamine or its monomethylated form attached to carbon 6 of the glucose moiety (Boland, S. et al. Phosphorylated glycosphingolipids essential for cholesterol mobilization in Caenorhabditis elegans. Nature Chem. Biol., 13, 647-654 (2017);  DOI) The ceramide moiety contained an iso-branched C17 sphingoid base of the phytosphinganine type (i.e. with a 4-hydroxyl group - normally considered a plant product) and amide-linked 2-hydroxy long-chain fatty acids with variable chain lengths (C22, C23 and C24). This lipid is shown to be essential for the development of C. elegans through its regulation of sterol mobilization (the organism requires an exogenous source of cholesterol). It is able to rescue larval arrest that has been induced by sterol starvation.

Formula of phosphoethanolamine-glucosylceramide

Related lipids had been reported earlier from a species of earth worm and from a marine worm, but with galactose as the carbohydrate moiety and with phosphocholine as the attachment, while phosphono analogues have been recorded from marine invertebrates (see my web page on glycosylceramides). However, the functions of these lipids have not been explored. Note that these lipids should be termed "phosphoglycosphingolipids", not "glycophosphosphingolipids", an important distinction that is explained for the glycerolipid equivalents here...

April 18th, 2018

Concerns over the nutritional effects of fatty acids with trans double bonds have created a need for methodologies that enable analysts to determine the nature and amounts of the trans isomers of polyunsaturated fatty acids that may be generated in the refining process of commercial oils. Two papers have just appeared on the topic. The first looks at geometric isomers of stearidonic acid (18:4(n-3)), which are isolated by silver ion chromatography and then subjected to structural analysis to determine the order of elution by GC (Delmonte, P. et al. Structural determination and occurrence in ahiflower oil of stearidonic acid trans fatty acids. Lipids, 53, 255-266 (2018);  DOI). The second is even more daunting technically as it involves docosahexaenoic acid isomers. I don't have access to the original publication, but from the abstract the authors use a very different approach involving epoxide intermediates (Menounou, G. et al. Trans lipid library: synthesis of docosahexaenoic acid (DHA) monotrans isomers and regioisomer identification in DHA-containing supplements. Chem. Res. Toxicol., 31, 191-200 (2018);  DOI).

I have seen (and cited in my literature survey pages for 2016) two publications dealing with the use of gas chromatography linked to vacuum ultraviolet spectroscopy as a means of identifying and quantifying trans-fatty acids in samples. Now a new publication describes an application of the technique to a much wider range of fatty acid types including those with branched-chains, cyclopropane rings and hydroxyl groups (Santos, I.C. et al. Analysis of bacterial FAMEs using gas chromatography-vacuum ultraviolet spectroscopy for the identification and discrimination of bacteria. Talanta, 182, 536-543 (2018);  DOI). I don't see such equipment supplanting GC-MS, but it may compliment it well.

I have just read a report that the owner of the Web of Science has purchased a software company that has a web-browser extension to simplify the process of finding and legally downloading scholarly publications. This will be incorporated as a tool that offers one-click access to journal articles to which we may have legal access without having to sign into the journal or go through an Institution's account. When it is implemented, it will make my weekly literature searches much easier.

April 11th, 2018

The Journal of Experimental Biology has published a special issue (March, 2018 vol. 221 (Suppl. 1) - open access) on the theme of "The biology of fat" with guest editors Raul K. Suarez and Hans H. Hoppeler. There is an eclectic array of topics, with brown fat, adipose tissue metabolism and the metabolic syndrome well to the fore. However, there are a number of interesting papers dealing with aspects of the subject less often encountered in main-stream publications, for example adipogenesis in fish and energy metabolism in migrating birds. I am always fascinated by novel functions of lipids, so I can recommend a paper on fats in over-wintering insects. Did you know that some insects can tolerate being completely frozen thanks to the presence of triacylglycerols containing acetate that remain liquid well below 0°C, while others contain glycolipids that serve as anti-freeze agents? An older story but one well worth recalling is the observation that dolphins and toothed whales have an organ in the head with mixtures of wax esters and triacylglycerols so arranged that they serve to focus sound during echolocation and hearing.

A cliché that I dislike intensely is "thinking outside the box", so I will refrain from using it when citing a new publication that makes use of clever chemistry in a procedure for isolating sphingoid bases (Gowda, S.G.B. et al. Facile chemoselective strategy toward capturing sphingoid bases by a unique glutaraldehyde-functionalized resin. ACS Omega, 3, 753-759 (2018);  DOI - open access). The authors utilize the selective but reversible reaction of glutaraldehyde with the 1,3-diol groups in sphingoid bases. By employing the functional groups bonded to a resin, they were able to develop a relatively simple procedure to concentrate a clean fraction of sphingoid bases for further analysis.

The journal Bioanalysis has devoted an issue (March, 2018) to the topic of "Bioanalytical techniques in lipidomics" (edited by D. Vuckovic). Some of the articles are open access.

Nature News reports that the EU is proposing a change in copyright law that might make life difficult for scientists in general and websites like this in particular. For example, publishers could demand a fee from any publication that quotes them in any way, including listing tabulated data. Although it is unlikely to be enforced, they could even demand a royalty for citing a paper. It would also "compel repositories of research articles to prevent uploads of copyrighted papers and other content" (this direct quotation could require a fee). Fortunately, any new law must be approved by the EU parliament and by member states before it can be enacted (here I have been careful to paraphrase the original). Not surprisingly, publishers are in favour of the proposals.

April 4th, 2018

Formula of jasmonoylisoleucinePlant oxylipins have been the subject of intensive study in recent years, and the jasmonates are especially important as the title of a new review makes clear (Koo, A.J. Metabolism of the plant hormone jasmonate: a sentinel for tissue damage and master regulator of stress response. Phytochem. Rev., 17, 51-80 (2018);  DOI). (+)-7-Jasmonoyl-isoleucine appears to be the key molecule as this is the only one known to have a specific receptor, although it is the precursor of at least 11 known metabolites many of which have biological activities in their own right. Jasmonic acid per se is a 12-carbon cyclic fatty acid derived from α-linolenic acid and with a cyclopentanone ring resembling that in mammalian prostaglandins (surely no coincidence) as a key structural feature. Together with the other plant oxylipins, jasmonates are an essential part of a complex interactive network of phytohormones that controls all aspects of plant growth and development and the manner in which plants adapt to the environment. As an example, next time you enjoy a plate of chips (French fries) you may care to recall that the glucopyranosyl derivative of tuberonic acid, derived from jasmonic acid after hydroxylation at C-12, induces tuber formation in potato plants through its influence upon gibberellic acid signalling. Jasmonates even enable plant to talk to each other, and when one is damaged by insect attack, volatile methyl jasmonate is released to be taken up by neighboring plants to stimulate them to set their own defence mechanisms in action.

Seed oil triacylglycerols have been the subject of intensive study because of their importance in commerce. Their biological role to supply energy and structural components to the developing plant embryo has not been neglected, and it has generally been assumed that the small concentrations of triacylglycerols in lipid droplets in vegetative tissues serve a similar purpose. However, a new review suggests that the latter may have many more dynamic functions (Yang, Y. and Benning, C. Functions of triacylglycerols during plant development and stress. Curr. Opinion Biotechn., 49, 191-198 (2018);  DOI). The authors discuss how triacylglycerol metabolism is involved in cell division and expansion, stomatal opening, and membrane lipid remodeling, while in reproductive tissues, they are important for organ formation and successful pollination.

In most plants and algae under phosphate deprivation, phosphatidylcholine in membranes is exchanged for digalactosyldiacylglycerols and/or betaine lipids. However, in a model marine diatom, it is replaced in part by a diglycosylceramide, suggesting that sphingolipids may be more important in these organisms than has been believed hitherto (Hunter, J.E. et al. Lipidomics of Thalassiosira pseudonana under phosphorus stress reveal underlying phospholipid substitution dynamics and novel diglycosylceramide substitutes. Appl. Environm. Microbiol., 84, UNSP e02034-17 (2018);  DOI).

Staying on a botanical theme, several correspondents have admired the Scottish thistles that adorn these web pages. My intention is merely to provide something appropriate, decorative and not too intrusive to brighten large areas of text and not simply to illuminate my origins. In fact, it does not always do to cast light on your ancestry as a family legend has it that about six generations back, an ancestor of mine was hung for piracy in Cornwall. We are quite proud of having a pirate in the family, but it is worrisome that he may have been an Englishman.


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Author: William W. Christie Updated: August 15th, 2018 Credits/disclaimer LipidWeb logo