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. The older entries are archived for at least a year in a separate web page here..
January 3rd, 2018
As a New Year gift to lipid analysts, I draw your attention to a 72 page open access publication reviewing NMR spectroscopy (1H, 13C and 31P) of lipids (Alexandri, E. et al. High resolution NMR spectroscopy as a structural and analytical tool for unsaturated lipids in solution. Molecules, 22, 1663 (2017); DOI). It is a large file at 34Mb, so you may need a fast broadband connection.
The lipid A (endotoxin) component of bacterial lipopolysaccharides is a fascinating complex molecule that serves to protect the organism from attack from external agencies, including antibiotics, but is a major reason for the virulence of pathogenic bacteria. Many factors are involved, including the number and nature of the fatty acid constituents, but the general mechanism of the immune response is usually considered to be a binding to a large hydrophobic pocket in a receptor such as toll-like receptor 4 (TLR4) via the lipid chains, while the phosphate groups can interact directly with the receptor leading to formation of a heterodimer complex that is active in immune signalling. However, a new publication demonstrates that the TLR4 receptor does not recognize the endotoxin of a rather nasty pathogen, Francisella novicida, which is thus able to evade the host innate immune system. Instead, this stimulates the cyclooxygenase-2-dependent inflammatory pathway and is responsible for the lethality of such infections through overproduction of proinflammatory effectors such as prostaglandin E2 (Scott, A.J. et al. Host-based lipid inflammation drives pathogenesis in Francisella infection. PNAS, 114, 12596-12601 (2017); DOI).
The regulation of cholesterol levels in animal tissues is a complicated topic involving innumerable factors, and I struggle to come to grips with it. One novel feature that has just come to light is that the first 100 amino acid in a key enzyme in cholesterol biosynthesis, i.e. squalene monooxygenase, is a proteasomal degradation signal or 'degron'. This sequence attaches reversibly to the ER membrane, and in the presence of excessive cholesterol levels, it is ejected and unravels to expose a hydrophobic patch, which then says "eat me" (Chua, N.K. et al. A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis. J. Biol. Chem., 292, 19959-19973 (2017); DOI).
December 20th, 2017
At this time of year, there is only one paper that I wish to highlight because of its appropriateness to the Christmas season, and happily it is open access (Morikawa, T., Matsuda, H. and Yoshikawa, M. A review of anti-inflammatory terpenoids from the incense gum resins frankincense and myrrh. J. Oleo Sci., 66, 805-814 (2017); DOI). It even has three wise men (persons?) as authors. I presume that the word "anti-inflammatory" in the title refers to "Peace on Earth and goodwill to all men".
Merry Christmas and a happy, healthy, prosperous and anti-inflammatory New Year to all my readers!
December 13th, 2017
In recent years, the potential for using natural lipids as pharmaceuticals to treat various disease states has become very evident. Outsiders such as myself are rarely aware of the many pitfalls in taking a new discovery from patent application through to clinical trials and commercial success. A new review discusses this in relation to palmitoylethanolamide and the specialized pro-resolving mediators (Hesselink, J.M.K. Fundamentals of and critical issues in lipid autacoid medicine: a review. Pain Therapy, 6, 153-164 (2017); DOI). For example, palmitoylethanolamide was proven to alleviate neuropathic pain in the 1990s, but the first company to patent and develop this for clinical purposes went out of business because of delays in the Italian licensing system. Now the patents have expired and there is no financial incentive for anyone else to take it on, although there seems little doubt that it is safe and effective. The first patent on the lipoxins was issued in 1984, but only one clinical pilot trial in atopic eczema can be identified so far.
I take some pleasure in reading of natural cholesterol derivatives with important health-giving properties, and one such is dendrogenin A (DDA), a naturally occurring conjugate of cholesterol and histamine. Its synthesis is greatly reduced in cancer cells, and it has now been shown to be a potent tumor suppressor that controls a nuclear receptor to kill cancers (Segala, G. et al. Dendrogenin A drives LXR to trigger lethal autophagy in cancers. Nature Commun., 8, 1903 (2017); DOI - open access).
There is a report in Nature News that Elsevier continues to have a problem with German universities in that negotiations have failed to end a long-term contract dispute. The aim of the universities, which will no doubt be supported by most scientists, is to reduce subscription prices and promote immediate open access. While I accept that commercial publishers must be allowed to make a profit, the last figure I saw for Elsevier was 36% of turnover and this seems grossly excessive. A new business model is surely required. When I read the report, I checked my personal data base of references that are cited in the Literature Survey section of the LipidWeb, and I found that nearly half were to Elsevier journals. This figure is certainly skewed in that I don't have access to many smaller publishers and many of the chemistry journals, not least those from ACS and RSC, but it does demonstrate the influence of Elsevier. If I can't read papers to update my pages here, I rarely cite them, although I do cite those in journals that are sufficiently public spirited to allow open access after 1-2 years.
December 6th, 2017
Most readers today will not need me to explain the importance of lipid mediators in biology, but this was not always so. I recall attending an ICBL Congress in 1968 when a keynote speaker described prostaglandins as "a drug in search of a disease"! (The only virtue of growing older is that you remember such things). The earliest true pharmaceutical to come into general use and probably still that most widely used is aspirin, which is now known to inhibit the synthesis of the prostaglandins and certain other eicosanoids or modify their nature via its action on the cyclooxygenases. A fascinating new review describes how the full potential of aspirin and many other pharmaceuticals could not have been realized without the knowledge gained from lipidomic studies on the eicosanoid patterns in tissues in various clinical conditions (Stephenson, D.J. et al. Lipidomics in translational research and the clinical significance of lipid-based biomarkers. Translat. Res., 189, 13-29 (2017); DOI). For example, by revealing the pattern of eicosanoids during cardiovascular disease or in patients with pre-eclampsia, it became evident that low-doses of aspirin had great therapeutic potential. Many other benefits from lipidomic studies to such disease states as neurodegenerative diseases, cancer, sepsis and wound healing are discussed also in this review.
The tag "et al." has never been more useful than in a new publication in the Journal of Lipid Research, which has 94 authors (I don't guarantee the accuracy of my count) (Bowden, J.A. et al. Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma. J. Lipid Res., 58, 2275-2288 (2017); DOI). John A. Bowden was fortunate in that his name is first in the alphabetical order of authors so takes pride of place in the list. Joking aside, I suspect that this will come to be regarded as a seminal paper in the science of lipidomics, although it is a pity that it is not open access. However, like me, you may still be able to get hold of a manuscript copy if not the final printed form via the journal.
November 29th, 2017
In plants, the external cuticle layer has many of the same functions as the skin in animals in that it acts to prevent water loss while providing a barrier against pathogenic bacteria and fungi as well as insect predators. Lipids play key roles in both although their natures are very different; in skin, ceramides and other sphingolipids are the essential components, but in plants there is a complex polyester that includes polyhydroxy and dibasic fatty acids and this is overlaid by a layer of wax. While some have argued that plant waxes are the most abundant lipids on earth, it is the polyester component of the cuticle that is attracting most interest at the moment because of its structural properties and the potential to modify it to increase crop yields or as a future source of bio-plastics. Incidentally, cutins from decaying plants are also the source of important lipid components of soils. The Journal of Experimental Botany has devoted a special issue to the topic with an introductory article that summarizes many of the key factors and is open access (Domínguez, E. et al. The plant cuticle: old challenges, new perspectives. J. Exp. Bot., 68, 5251-5255 (2017); DOI).
Among the novel lipids of skin are ceramides containing estolide linked fatty acid constituents. However, it is those with free carboxyl groups or 'FAHFA' (Fatty Acid ester of Hydroxy Fatty Acid) in other tissues that continue to fascinate. A range of (O-acyl)-ω-hydroxy-fatty acids (the hydroxyl group is terminal not centrally located) with up to 52 carbon chain lengths have been found in equine amniotic fluid, together with many other interesting lipid species (Wood, P.L. et al. Lipidomics of equine amniotic fluid: Identification of amphiphilic (O-acyl)-ω-hydroxy-fatty acids. Theriogenology, 105, 120-125 (2018); DOI). Similar fatty acid estolides have been found in sperm and meibomian glands, but their function is still a matter for speculation.
The journal Seminars in Immunology has devoted a special issue (Volume 33, Pages 1-74, October 2017) to the topic of "Leukotriene B4 mediated inflammation" (edited by Bodduluri Haribabu).
November 22nd, 2017
Of all the health food supplements that are available, it appears that omega-3 fatty acids from fish oil preparations are the most popular. While reputable manufacturers take great pains over the quality of their products, they have no control of how they are stored in supermarkets or whether consumers store them properly or simply let them sit in medicine cabinets.· I am sure that oxidation products often develop rapidly, although off-flavours may be disguised by the encapsulation process.·· A new review summarizes the biological properties of compounds derived from peroxidation of omega-3 polyunsaturated fatty acids,· including aldehydes, isoprostanes· and more (Wang, W. et al. Chemistry and biology of ω-3 PUFA peroxidation-derived· compounds. Prostaglandins Other Lipid Mediators, 132, 84-91 (2017); DOI).· Many potential adverse effects are known, and the authors are concerned that variable amounts of such impurities· might explain the mixed results obtained in some nutritional studies. Personally, I prefer fresh fish to fish oil supplements.
S-Palmitoylation is increasingly being seen as an important way· of regulating the activities of potential membrane proteins.· In humans, 23 palmitoyl transferases are known to exist with a conserved cysteine-rich domain containing· a distinctive aspartate-histidine-histidine-cysteine (DHHC) motif, which is required for activity.· On the other hand, no conserved amino acid sequence has yet been identified in target proteins.· A new open access publication describes interesting mass spectrometry methodology to reveal· that there is a random palmitoylation process that depends simply upon the accessible· of cysteines in proteins to the palmitoyl transferases (Rodenburg, R.N.P. et al. Stochastic palmitoylation· of accessible cysteines in membrane proteins revealed by native mass spectrometry. Nature Commun., 8, 1280 (2017);· DOI).
November 15th, 2017
The hedgehog proteins are among my favourite molecules as they stick up two metaphorical fingers to nutritionists. The first such finger is cholesterol, which is covalently bound to the C-terminus, while the second is palmitic acid covalently bound to the N-terminus. Although they are anathema in some quarters, the vital importance of the two much maligned lipid components is clearly demonstrated since hedgehog proteins have a major role in signalling during the differentiation of cells in the development of all embryos from Drosophila to fish to humans and are required for an extensive range of processes, from the control of left-right asymmetry of the body to the specification of individual cell types within the brain and limb development. They are the subject of a new open access review (Blassberg, R. and Jacob, J. Lipid metabolism fattens up hedgehog signaling. BMC Biology, 15, 95 (2017); DOI).
Membrane microdomains termed 'rafts' have long been believed to be formed spontaneously in the outer leaflet of the plasma membrane by the physical chemical association of cholesterol, sphingolipids and membrane proteins. They act to compartmentalize and provide a platform for the last and thereby separate different biochemical functions. However, there is a conflicting view of the prevailing raft hypothesis based on studies by high-resolution secondary ion mass spectrometry that suggests that sphingolipids are concentrated in micrometer-scale membrane domains while cholesterol is evenly distributed within the plasma membrane. In this model, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with cholesterol. An open access review, published earlier this year, discusses this alternative theory (Kraft, M.L. Sphingolipid organization in the plasma membrane and the mechanisms that influence it. Front. Cell Dev. Biol., 4, 154 (2017); DOI).
I was under the impression that I had a good understanding of the nature of bile acids, which are important cholesterol metabolites with essential functions in digestions and signalling. However, I have just come across a paper that describes a small group of bile acids with planar structures of which I had no previous knowledge (Shiffka, S.J. et al. Planar bile acids in health and disease. Biochim. Biophys. Acta, Biomembranes, 1859, 2269-2276 (2017); DOI). These are found in humans during infancy and in a few disease states, but not otherwise. In evolutionary terms, they may be related to the ancestral bile acids.
November 8th, 2017
Another special journal issue deals with the important topic of specialized pro-resolving mediators, i.e. resolvins, protectins and maresins, (Dalli, J. (Editor) The physiology and pharmacology of specialized pro-resolving mediators. Molecular Aspects of Medicine Volume 58, Pages 1-130 (December 2017)). The editor's own contribution is open access and has the intriguing title of "Does promoting resolution instead of inhibiting inflammation represent the new paradigm in treating infections?" Uncontrolled inflammation as occurs during sepsis is an increasing problem in our hospitals, and the resolvins, protectins and maresins have been shown to "actively reprogram the immune response to promote clearance of invading pathogens, and counter-regulate the production of inflammation-initiating molecules". Clinical trials of these lipids and mimetics against a number of inflammatory conditions, including sepsis, are now in progress and they are discussed in other reviews in this issue.
In contrast, cholesterol 5,6-epoxide formed non-enzymatically was for some time believed to be a causitive agent in cancer, but it has now been established that downstream metabolites are in fact responsible (Voisin, M. et al. Identification of a tumor-promoter cholesterol metabolite in human breast cancers acting through the glucocorticoid receptor. PNAS, 114, E9346-E9355 (2017); DOI). A cholesterol epoxide hydrolase converts cholesterol 5,6-epoxide into cholestane-3β,5α,6β-triol, which is transformed by 11β-hydroxysteroid-dehydrogenase-type-2 into the oncometabolite 6-oxo-cholestan-3β,5α-diol. By binding to the glucocorticoid receptor, this last metabolite stimulates the growth of breast cancer cells. It is hoped that targeting the enzymes involved in this metabolic process may lead to new treatments for breast and other cancers.
It has been less easy to establish definitively the biological effects of other oxysterols as so much cholesterol may be present in experiments in vitro that unwanted metabolites may be introduced inadvertently. However, there is good evidence for the involvement of 27-hydroxycholesterol as an endogenous and selective modulator of estrogen receptors with implications for a number of disease states including neurodegenerative diseases, atherosclerosis, osteoporosis and some cancers (He, S.S. and Nelson, E.R. 27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator. Maturitas, 104, 29-35 (2017); DOI).
Every year I seem to find a news item highlighting the poor job prospects for new PhD students and I usually predict that nothing will change. This is still true - see Nature News!
November 1st, 2017
While I have been enjoying the sunshine of the Canary Islands, the world of lipids has been turning rapidly. It seems most unfair that after returning from 30°C on a beach in Gran Canaria to 11°C and thermal underwear in Scotland, in addition to scanning many new research papers and other chores, I have now to try to assimilate three special review volumes to update my Lipid Essentials pages, i.e. "Focus on plasmalogens" in FEBS Letters (Volume 591, Issue 20) and open access, "Oxysterols and Phytosterols in Human Health" (edited by Charbel Massaad, Luigi Luliano and Gérard Lizard) in Chemistry and Physics of Lipids (Volume 207, Part B) and "Microbe and host lipids", edited by Jérôme Nigou, Lhousseine Touqui, Michel Record in Biochimie (Volume 141).
Sometimes it is the science oddities rather than major new research findings in terms of lipid metabolism that catch the eye. For example, I was intrigued by a report in the popular scientific press of preen gland lipids being identified in the fossil of a 48-million-year-old bird. It appears that the composition was sufficiently similar to that of the waxes in modern birds to enable an unequivocal identification.
Another fascinating if more relevant observation in relation to human health is carried in a paper that demonstrates that gangliosides are essential for hearing in that their presence in membrane rafts is required to maintain the structural and functional integrity of hair cells in the ear (Inokuchi, J. et al. Gangliosides and hearing. Biochim. Biophys. Acta, General Subjects, 1861, 2485-2493 (2017); DOI). If you have an interest in these sphingoglycolipids there is a second publication in the same journal issue dealing with gangliosides, rafts and inflammation.
October 18th, 2017
For decades, plant biochemists have been looking for a magic bullet that will enable them to alter the lipid composition of membranes in plants to make them less sensitive to cold. Some progress has been made by introducing desaturase genes, and the composition of phosphatidylglycerol appears to be especially important. However, a new review provides a broader context to the problem by comparing the factors that differentiate the model plant Arabidopsis from a close relative that is especially hardy (Barrero-Sicilia, C. et al. Lipid remodelling: Unravelling the response to cold stress in Arabidopsis and its extremophile relative Eutrema salsugineum. Plant Sci., 263, 194-200 (2017); DOI). It is evident that there are many different factors involved including many compounds other than lipids (sugars, nitrogen compounds and proteins) that are required to conserve membrane integrity during cold acclimatization. Then, we have to understand the role of signalling lipids in controlling how membranes respond to change, where it appears that sphingolipid analogues of sphingosine-1-phosphate are especially important. Despite this complexity, the authors seem to be confident that further lipidomic studies in combination with genome editing in a precise manner "will enable the development of breeding strategies that deliver climate resilient crops."
The nature of the challenges to modifying lipid compositions in plants is illustrated by a further review in the same journal issue, where the authors point out that to introduce new fatty acids of potential industrial interest to crop plants it is rarely possible to introduce a single biosynthetic gene. It is always necessary to add futher genes for enzymes that can handle the new fatty acid and complete the transfer to a safe esterified state (Aznar-Moreno, J.A. and Durrett, T.P. Metabolic engineering of unusual lipids in the synthetic biology era. Plant Sci., 263, 126-131 (2017); DOI).
I suppose it was not really a surprise to learn that Elsevier and the American Chemical Society have filed a lawsuit with the aim of removing copyrighted material from ResearchGate (see Nature News). I have mixed feelings about this, coloured of course by my personal circumstances. My former employer allows me access to a wide range of biological publications from the big three publishers together with a range of journals to which it subscribes, but I can't access chemistry journals or many of those with a medical slant. While I could use interlibrary loan facilities, this bears a significant cost and I cannot justify this when I am only going to use the information I glean for my website and not for research purposes. The prices required by journals for digital access are so unreasonable - far higher than those for interlibrary loan photocopies - that it is no wonder that scientists turn to ResearchGate in the hope of finding copies there. I have to confess that I do this from time to time, and often find preprints rather than the final publications and these are more than adequate for my purposes. Would this be a fair compromise?
As you may guess from the title, I read another review with great interest this week (Bustos, V. and Partridge, L. Good ol' fat: links between lipid signaling and longevity. Trends Biochem. Sci., 42, 812-823 (2017); DOI). While it is a fascinating account of the use of the nematode worm Caenorhabditis elegans in studies of this kind, it is apparent again that there is no magic bullet alas. However, there is clear evidence that dietary restriction helps, and oleoylethanolamide does extend life in worms at least via its signalling properties. There is also something to be said for higher relative dietary proportions of oleate in general. If it will keep me compos mentis as well for longer, I will volunteer as a guinea pig.
Last month, I highlighted a multiauthor paper describing protocols for the use of NMR spectroscopy for the analysis of lipoprotein classes. Now a new review publication provides a general overview of the techniques involved (Aru, V. et al. Quantification of lipoprotein profiles by nuclear magnetic resonance spectroscopy and multivariate data analysis. Trends Anal. Chem., 94, 210-219 (2017); DOI).
October 11th, 2017
Developments in mass spectrometric methodology has turned the analysis of lipids into a new science - lipidomics, but I must confess that I tend to pay relatively little attention to the applications of nuclear magnetic resonance spectroscopy to lipid science. The latter lacks the sensitivity of MS methods, but it can make an invaluable contribution to lipid analysis and structure identifications nonetheless, especially when sample size is not limiting. Indeed, NMR spectroscopy may have advantages in settling stereochemical problems. A new review of the subject is therefore timely (Li, J. et al. Applications of nuclear magnetic resonance in lipid analyses: An emerging powerful tool for lipidomics studies. Prog. Lipid Res., 68, 37-56 (2013); DOI). If the DOI link doesn't work, blame Elsevier.
A new review on the subject of "steryl esters" in BBA reminded me that some years ago when I raised a nomenclatural point with IUPAC-IUB, they rebuked me for using the generic term "cholesteryl esters", which I was told should correctly be termed "cholesterol esters". "Cholesteryl" should be applied only when describing individual lipid species, e.g. cholesteryl palmitate, cholesteryl oleate, etc. Over to you Lipid Maps!
Just has Christmas comes earlier every year in the shops at least, so does the new publishing year roll out earlier. In my literature survey last month, I cited my first 2018 reference! The journal Food Chemistry wins the race every year.
October 4th, 2017
Humans differ from all other animals in that we do not make the sialic acid N-glycolylneuraminic acid (Neu5Gc) for incorporation into gangliosides and glycoproteins. This is believed to have occurred during evolution soon after we diverged from a common ancestor with the great apes and may have had profound implications for the development of the human brain. It could also mean that there might have been a fertility barrier between us and other species of hominids. Proving these conjectures has seemed impossible, but it has now been established that sufficient glycoproteins linked to Neu5Gc are present in intact form in fossil bones to enable determination of its presence. It will be fascinating to see how the story now unfolds. There is a popular account of the research in Science Daily with a link to the original publication for those needing further details.
Just as I was working my way through one special issue, Biochimica Biophysica Acta has brought forward another that deals with "Bacterial Lipids" and edited by Russell E. Bishop; I suspect it will keep me busy updating my web pages here for some time.
A fascinating story has emerged in a new publication that demonstrates how the liver undergoes a metabolic switch to provide fuel for brown fat thermogenesis by producing acylcarnitines. Under cold stimulation, white adipocytes release free fatty acids for acylcarnitine production in the liver to be supplied in the circulation to brown adipose tissue. At the same time, uptake of acylcarnitines into white adipose tissue and liver is blocked (Simcox, J. et al. Global analysis of plasma lipids identifies liver-derived acylcarnitines as a fuel source for brown fat thermogenesis. Cell Metab., 26, 509-522.e6 (2017); DOI). While the quantitative aspects appear to require further work, the process is certainly an elegant one. I don't have access to the original paper yet, but the journal issue contains a commentary or 'preview' that describes the work and is accessible (if you know where to look via Google).
September 27th, 2017
While my weekly literature searches keep me reasonably up-to-date, the algorithm I use is far from perfect and I have just come across a fascinating lipid story that started in 2012 and continues to the present. First a little background - choanoflagellates are motile microbial eukaryotes that live in aquatic environments and feed on bacteria. They are believed to be the closest living relatives of animals and are normally unicellular. However, it has now been demonstrated that on exposure to novel sulfonolipid analogues of ceramides related to the capnoids and produced by Algoriphagus machipongonensis, a marine bacterium that serves as its prey, the choanoflagellate, Salpingoeca rosetta, forms multicellular 'rosettes' in a manner that may provide insights into how multicellularity evolved in animals. Two such lipids have been isolated and characterized and they have been termed 'Rosette-Inducing Factors' - RIF-1 (illustrated) and RIF-2. Both have capnoid bases attached to 2-hydroxy,iso-methylbranched fatty acids, but RIF-2 differs from RIF-1 in the nature of the capnoid base component. S. rosetta is extraordinarily sensitive to RIF-1 and is induced to form rosettes at femtomolar (10-15M) concentrations. A second lipid class, lysophosphatidylethanolamines, produced also by the symbiotic bacteria elicits no response on its own but acts synergistically with the RIFs to maximize the activity of the latter.
A third lipid class now enters the picture as the same bacterial species also produces an inhibitor of rosette formation termed 'Inhibitor of Rosettes (IOR-1)' in the form of a further novel sulfonolipid, which is related structurally to the capnoid bases but with a hydroxyl group replacing the amine group to give the rare syn-diol configuration, i.e. 2S, 3R stereochemistry. It has been determined that there is an absolute requirement for the observed stereochemistry for all of these metabolites to exert their functions. To follow the story in greater detail, see the latest publication from the research group responsible for the work (Woznica, A. et al. Bacterial lipids activate, synergize, and inhibit a developmental switch in choanoflagellates. PNAS, 28, 7894-7899 (2016); DOI).
September 20th, 2017
Although the evaporative-light scattering detector (ELSD) has its limitations in terms of linearity of response and sensitivity, it was the first truly universal detector for HPLC of lipids at a time when mass spectrometry interfacing was prohibitively expensive for most researchers. It enabled great strides in the development both of mobile and stationary phases for lipid separations and still has value for this purpose today. When charged aerosol detectors (CAD) were introduced, they seemed a step forward but they have never taken off. In part, this seemed to be because impurities in solvents caused problems and ionic species in mobile phases, which are necessary for elution of phospholipids, were especially troublesome. As liquid chromatography-mass spectrometry systems have become more affordable, the perceived need for alternative detectors may have lessened, but I believe the ELSD and CAD will remain useful tools, especially for development of novel elution systems and for semi-preparative applications (with stream splitters). A new publication presents a more positive view of the CAD than I have seen up till now, while also comparing the merits of various ionization techniques employed in mass spectrometry interfacing; atmospheric pressure photoionization (APPI) seems a clear winner (Abreu, S. et al. Optimization of normal phase chromatographic conditions for lipid analysis and comparison of associated detection techniques. J. Chromatogr. A, 1514, 54-71 (2017); DOI). The paper also describes a rather novel and comprehensive elution scheme for normal-phase separation of lipid classes with silica as the stationary phase and a complex gradient in the mobile phase with ethyl acetate as a major component.
When I saw that a new review had been published on lipids in plant defense, I immediately assumed that this would deal primarily with the oxylipins and then mainly with jasmonates, but it proved much more than that. In fact, it covers a full range of lipids from fatty acids, via complex lipids to wax esters, and provides a fascinating and comprehensive overview of the subject (Lim, G.H. et al. Fatty acid- and lipid-mediated signaling in plant defense. Annu. Rev. Phytopath., 55, 505-536 (2017); DOI).
The latest online issue of Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids (Volume 1862, Issue 10, Part B, Pages 1129-1284 (October 2017)) covers the topic of "Recent Advances in Lipid Droplet Biology" and is edited by Rosalind A. Coleman and Matthijs K.C. Hesselink.
September 13th, 2017
"A tale of two lipids" may sound Dickensian, but it aptly describes a paper drawn to my attention by the newsletter of the Fats of Life; in truth, it is anything but Dickensian (Houthuijzen, J.M. et al. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance. FASEB J., 31, 2195-2209 (2017); DOI). I have encountered hexadeca-4,7,10,13-tetraenoic acid or 16:4(n-3) at trace levels from time to time in marine samples, but never in animal tissues. Yet it is generated when platinum salts are administered as part of an anticancer chemotherapy regime where it induces systemic resistance to a broad range of DNA-damaging effects. The new study demonstrates that this fatty acid acts via a specific receptor to induce the synthesis in macrophages of the second unusual lipid in the tale, i.e. lysophosphatidylcholine containing the fatty acid 24:1, and this is also shown to be a resistance-inducing lipid mediator. Again, I don't recall seeing this particular molecular species when analysing animal lipids, though I must admit that it would be easy to overlook.
Nature has an interesting story concerning "predatory journals", which I suppose must be defined as those designed to milk revenue from researchers rather than to inform. While I have heard this epithet applied to the big three commercial publishers from time to time, the authors appear to refer to about ~2000 other journals, which are often published in third world countries and lack proper editorial boards or refereeing panels. It seems that many reputable authors are using them while unaware of the true situation. I can think of a few review articles, which have come from such journals and which I may have cited in this website from time to time because they appeared useful to me in updating my web pages, especially as many are part of the open access trend. In fairness to myself, I usually check whether the authors come from reputable institutions. Unfortunately, no one seems to have any idea what to do about the problem other than to keep researchers informed of the worst examples, and I suspect any solution would have to emerge sector by sector.
The journal Neuropharmacology (Volume 124, Pages 1-170 (15 September 2017)) is a special issue devoted to the topic of "A New Dawn in Cannabinoid Neurobiology", edited by Joseph F. Cheer and Yasmin L. Hurd. Many of the papers deal with the endocannabinoids.
September 6th, 2017
Sulfoquinovosyldiacylglycerols are key lipids in photosynthesis and thence for the survival of all advanced life as I discussed in my blog earlier in the year. A recent paper demonstrates that the positional distributions of fatty acids in this lipid can be determined by mass spectrometry (Granafei, S. et al. Unambiguous regiochemical assignment of sulfoquinovosyl mono- and diacylglycerols in parsley and spinach leaves by liquid chromatography/electrospray ionization sequential mass spectrometry assisted by regioselective enzymatic hydrolysis. Rapid Commun. Mass Spectrom., 31, 1499-1509 (2017); DOI). One of the tools the authors used to validate their results was to generate the 2-monoacyl-sn-glycerol species by the action of a regiospecific lipase (although the positional data are not tabulated). A few weeks ago I bemoaned the fact that data for positional distributions of fatty acids in complex glycerolipids were only rarely published nowadays, as this is much easier for comparison purposes (and arguably for studies of biological functions) than vast tables of molecular species data. While it is technically possible to accomplish this by MS, I suspect that the precision of the methodology leaves something to be desired. This paper has inspired me to consider whether a useful complementary approach to the analysis of phospholipids especially might be to analyse lipid extracts before and after hydrolysis by enzymes that are specific for either the sn-1 or sn-2 positions, e.g. the sn-1 selective hydrolase used in the above study or an sn-2 specific enzyme such as the phospholipase A2 of snake venom. I would love to see a paper tabulating comparison data for stereospecific distributions of fatty acids in any complex glycerolipid obtained by mass spectrometry with and without enzyme hydrolysis and ideally alongside data obtained by classical methods. It might be a useful student project for someone.
Lysoglycosphingolipids are only rarely discussed in the literature, but they do have considerable biological importance and a new publication describes new sensitive methodology to determine their occurrence in body fluids in relation to screening for sphingolipidoses (Pettazzoni, M. et al. LC-MS/MS multiplex analysis of lysosphingolipids in plasma and amniotic fluid: A novel tool for the screening of sphingolipidoses and Niemann-Pick type C disease. PLOS One, 12, e0181700 (2017); DOI).
If my knowledge of the practicalities of mass spectrometry is somewhat outdated, I have to confess that my understanding of what can be accomplished by NMR spectroscopy has fallen even further behind. However, I do my best to keep up and read with great interest a new open access publication dealing with the use of this technique in the analysis of lipoproteins (Centelles, S.M. et al. Toward reliable lipoprotein particle predictions from NMR spectra of human blood: an interlaboratory ring test. Anal. Chem., 89, 8004-8012; DOI). I remember well how tedious it was to analyse lipoprotein classes by ultracentrifugation or high-performance liquid chromatography. This new paper describes methodology that has advantages in terms of high reproducibility and speed, and appears to be especially suitable for studies involving large numbers of subjects. The separation techniques will always be needed, but the more information that can be obtained by other means the better especially when standardized protocols are available.
Older entries in this blog are archived for at least a year here..
|Author: William W. Christie||Updated: January 03th, 2018||Credits/disclaimer|