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).

June 12th, 2019

Formula of DiEpHEDEThree years ago in this blog, I highlighted a publication describing a novel eicosanoid with an unusual structure. It was termed dioxolane DXA3 and subsequently was found to have fascinating biological properties. The latter have not changed, but it appears that the structure proposed originally was wrong, and it has now been established that it is in fact a di-epoxide or 8,9‑11,12‑diepoxy-13-hydroxyeicosadienoic acid (8,9-11,12-DiEp-13-HEDE or DiEpHEDE). Of course, this is just as interesting from a biosynthetic standpoint as a dioxolane structure, especially as the cyclooxygenase 1 is the key biosynthetic enzyme (Kornilov, A. et al. Revising the structure of a new eicosanoid from human platelets to 8,9‑11,12-diepoxy-13-hydroxyeicosadienoic acid. J. Biol. Chem., 294, 9225-9238 (2019);  DOI - open access as author's choice).

A further open access bargain deals with the recent developments in oxysterol research (Griffiths, W.J. and Wang, Y.Q. Oxysterol research: a brief review. Biochem. Soc. Trans., 47, 517-526 (2019);  DOI). It has become apparent that these are intimately involved in innumerable biochemical processes of which many are relevant to human diseases, including neurodegenerative diseases and cancer. They are also important in tissue development through their involvement in the regulation of the activities of hedgehog proteolipids, among my favourite lipid molecules as they contain both cholesterol and palmitic acid, which are covalently bound. Technically, these oxysterols can be hard to study because they tend to be minor components in the presence of relatively large amounts of cholesterol, which is liable to autoxidation during processing. It may be a while before we can hand over their analysis to robots, so lipid analysts will continue to be gainfully employed.

June 5th, 2019

It has long been known that palmitoleic acid or cis-9-16:1 is a bit special and indeed has been termed a lipokine. For example, it is essential for the function of Wnt proteins in animal development. Now, another isomer, i.e. cis-10-16:1 isolated from a bacterial species, has been found to have distinctive anti-inflammatory properties (Smith, D.G. et al. Identification and characterization of a novel anti-inflammatory lipid isolated from Mycobacterium vaccae, a soil-derived bacterium with immunoregulatory and stress resilience properties. Psychopharmacology, in press (2019);  DOI). It is shown to upregulate many genes associated with signalling via its action upon peroxisome proliferator-activated receptor alpha (PPARα). Double bonds in even-numbered positions in monoenes are rather unusual, and one in position 10 may be unique (please correct me if I am wrong). Another interesting feature is that the fatty acid appears to be esterified into triacylglycerols as a single molecular species in the organism.

I mentioned a fascinating short review on aspirin in a recent blog, including its effects upon prostaglandin synthesis. It also a factor in the biosynthesis of the so-called aspirin-triggered specialized proresolving mediators produced from docosahexaenoic acid, i.e. the aspirin-triggered resolvins (AT-RvDs) and lipoxins (AT-LXs). It has now been demonstrated that AT-RvDs mediate the anti-tumour activity of aspirin. I can do no better than quote from the abstract - "Thus, the pro-resolution activity of AT-resolvins and AT-lipoxins may explain some of aspirin's broad anticancer activity. These AT-SPMs are active at considerably lower concentrations than aspirin, and thus may provide a nontoxic approach to harnessing aspirin's anticancer activity" (Gilligan, M.M. et al. Aspirin-triggered proresolving mediators stimulate resolution in cancer. PNAS, 116, 6292-6297 (2019);  DOI). We can but hope that clinical studies will soon prove their efficacy.

The British Journal of Pharmacology, Volume 176, Issue 8 has a themed Section: "Eicosanoids 35 years from the 1982 Nobel: where are we now?" with guest editors: Roderick J. Flower and Timothy D Warner.

May 29th, 2019

Scottish thistleMy recent blog-free holiday in Gran Canaria has provoked some reflection. When I started writing for the WWW in my supposedly retirement years, my first task was to set up my mass spectrometry pages. Then, I was aware that at the time (pre Lipid Maps) there was little else of value to students of lipid science - chemistry, biochemistry, physiology - that was open access. I had written a review of triacylglycerol composition and metabolism some years earlier, so it was not difficult to update and reformat this in a manner suited to the internet, and I hoped to make a small contribution in this way. However, on reflection, I thought that this should be balanced by a similar web page on a phospholipid, so I produced a similar web page on phosphatidylcholine. I was clear at the outset that I was aiming to help students and young scientists - not experts in the field - though I hoped that the reading list provided would assist the latter.

The Lipid Essentials section of the web site came into existence then in a relatively unplanned way as I continued to tackle individual lipid classes one at a time over a number of years. Of course, I was not omniscient then (or now), so I learned a great deal myself during this process. Writing for the WWW turned out to be an iterative process, as it is so easy to update web pages as I become aware of further information or new publications on my topics, or simply find a better way to explain some aspect. Nearly 20 years into my task, I continue to find stimulation in this activity, and I still have plenty of time for my family, garden, etc.

My background in lipid chemistry governed my approach, but I occasionally look back to consider whether I could have tackled it in a different way. For example, it is evident that there is a complex interplay among the innumerable lipid species in cells, and it can be difficult to convey this adequately in a web page devoted largely to a single lipid class, even with the use of hyperlinks between pages. While this is especially true for the oxylipins, it is also relevant for all complex lipids in membranes. These thoughts were stimulated in part by a review dealing with lipids as cells divide (Storck, E.M. et al. Lipid cell biology: a focus on lipids in cell division. Annu. Rev. Biochem., 87, 839-869 (2018);  DOI). In this process, a host of different lipids with different functions are involved in an integrated manner, and I am somewhat at a loss to see how I can incorporate this information adequately into so many different web pages on this site. A further paper to show the complexity of lipid interactions that is difficult to fit into my approach deals with the sneaky way viruses hijack many aspects of cellular lipid metabolism for their own nefarious purposes (Vieyres, G. and Pietschmann, T. HCV pit stop at the lipid droplet: refuel lipids and put on a lipoprotein coat before exit. Cells, 8, 233 (2019);  DOI).

I am content to continue with my existing plan for this website, but there must be many scientists out there who are nearing retirement and might consider the production of complementary websites with deeper insights into aspects of lipid science or with a more integrated approach to the subject. Over to you!

May 8th, 2019

If I have to select a single lipid that is attracting particular interest at present, it would have to be the epoxides of polyunsaturated fatty acids, both eicosanoids and docosanoids. Any number of publications have crossed my desk in recent weeks, and the most recent is a review article (Sausville, L.N. et al. Cytochrome P450 epoxygenases and cancer: A genetic and a molecular perspective. Pharmacol. Therapeut., 196, 183-194 (2019);  DOI). In many of their functions, epoxy-eicosanoids derived from arachidonic acid are believed to be beneficial towards human health, but not in relation to cancer where they are pro-angiogenic and promote tumor development and growth. The dihydroxy acids formed by ring opening of such epoxides seem to be regarded universally as harmful. On the other hand, the epoxy-fatty acids derived from eicosapentaenoic and docosahexaenoic acids inhibit angiogenesis and are protective against certain pathological conditions that include cancer. Life is complicated.

Next, a publication in which the title contains the worst pun of the year (Dixit, D. et al. Secrets and lyase: Control of sphingosine 1-phosphate distribution. Immun. Rev., 289, 173-185 (2019);  DOI). All joking aside, this seems to be a fascinating approach to the understanding of the complex problem of the multiple functions of sphingosine 1-phosphate in tissues.

My last publication today is surely a sign of the times (Lee, C.W. et al. Lipidomic profiles disturbed by the internet gaming disorder in young Korean males. J. Chromatogr. B, 1114, 119-124 (2019);  DOI). While a companion study of cell phone addiction and plasma lipids might now be relevant, where would we get an appropriate control group? I am not sure of any real relevance to lipids, and I confess that I should not be flippant about what is obviously a real problem for some.

May 1st, 2019

There is an interesting exchange of letters between H.S. Hansen and W.L. Smith in the latest issue of the Journal of Biological Chemistry (Issue 17) on the essential functions of linoleic acid in its own right, as opposed to as a precursor of arachidonic acid, and thence of the prostaglandins and other eicosanoids. Both agree on the vital role of linoleic acid as a precursor of hepoxilin-like compounds in skin, though perhaps the role in the specific skin ceramides should also be mentioned. In addition, it perhaps should be noted that oxygenated linoleate metabolites are the most abundant oxylipins in plasma in both free and esterified forms, and these have a range of biological functions - mainly with negative implications as far as I can see. Similarly, nitro-metabolites of linoleate may have important biological functions, though most current research appears to be with oleate isomers as these are more readily accessible by chemical synthesis. Indeed, conjugated linoleate, probably derived from linoleate per se, is by far the most active precursor for nitro fatty acids. N-linoleoyl ethanolamide is one of the main acylethanolamides in animal tissues; does it have any specific functions? All of these linoleate products may potentially be involved in its essentiality.

A subsidiary question is whether arachidonic acid has biological functions other than as a source of eicosanoids, and of course the endocannabinoids are important examples of this. Some years ago, A.R. Brash published a review on the topic (Brash, A.R. Arachidonic acid as a bioactive molecule. J. Clin. Invest., 107, 1339-1345 (2001);  DOI), and perhaps a revised and updated version might be timely (although it is quite possible that I have missed something). Finally, does α-linolenic acid have any essential functions in animal tissues other than as a precursor of long-chain polyunsaturated fatty acids of the n-3 family? As far as I understand it, the consensus at present appears to be no, but I await correction.

Dawn Cotter has been responsible for the weekly appearance of this blog on the LIPID MAPS® Lipidomics Gateway. Soon now, the complete LipidWeb will be duplicated there thanks to her efforts.

April 24th, 2019

Scottish thistleIt is not difficult to understand how so many of the oxylipins derived from essential fatty acids can interact physically with receptors, enzymes and other proteins with such specificity. After all, they contain double bonds, ring structures and/or oxygen molecules in highly stereospecific arrangements to favour specific interactions, and natural selection has designed them for such purposes. Even a relatively simple molecule, such as palmitoleic acid with only a single 9-cis double bond in the chain, is uniquely recognized by the enzymes involved in the function of Wtn proteins. However, when chain-length is the only structural feature of a fatty acid, it is sometimes harder to understand how specificity can be achieved.

The source of octanoic acid for its unique use for activation of ghrelin, has recently been identified as synthesis de novo from long-chain fatty acids by β-oxidation in ghrelin-producing cells, and proximity of the relevant enzymes may contribute to specificity. Then, we now have some understanding of distinctive acylations as in the N-myristoylation or S-palmitoylation of proteins, where it now seems that interactions between binding proteins and acyltransferases may provide an explanation for how these fatty acids are selected (see our web page on proteolipids). Of course, it has long been known how desaturases recognize saturated fatty acid precursors. Now a new, highly specific function for myristic acid has been described (Iwata, K. et al. Myristic acid specifically stabilizes diacylglycerol kinase δ protein in C2C12 skeletal muscle cells. Biochim. Biophys. Acta, 1864, 1031-1038 (2019);  DOI). Early biochemistry text books considered saturated fatty acids as dangerous in nutrition in excess, but otherwise as relatively inert molecules from a physiological standpoint; they were only present in tissues as a source of energy or as building blocks of membrane lipids. Those scientists with an interest in sphingolipids have always known better! I suspect that every fatty acid that we encounter in animal tissues has some vital biochemical function, although we may not yet know it.

April 17th, 2019

A few weeks ago, I expressed surprise that research on sphingosine-1-phosphate covered a span of 50 years. This now pales into insignificance with a new publication (Montinari, M.R. et al. The first 3500 years of aspirin history from its roots - A concise summary. Vasc. Pharm., 113, 1-8 (2019);  DOI). Of course there were no Proceedings of the Sumerian (or Egyptian) Academy of Sciences back then, but the Ebers Papyrus (1534BCE) apparently reports the use of willow bark as a painkiller and antipyretic. A mere 1000 years later, Hippocrates was aware of the medicinal properties of this plant family, but the true science of the salicylates began in the late 1700s. As the review recounts, we now know, thanks to the work of Sir John Vane and colleagues, that the mechanism of action of aspirin and other non-steroidal anti-inflammatory drugs is the dose-dependent inhibition of prostaglandin biosynthesis via its action upon cyclooxygenases. Why not put your feet up and read it during your next coffee break - at least it is a change from Brexit?

The effects of the Ebola virus on the lipid metabolism of patients with the disease was also mentioned in an earlier blog. Now a new review describes how this virus (and others) is able to take phosphatidylserine from the inner layer of the host plasma membrane and externalize it on the viral envelope to exploit the host apoptotic clearance machinery to enhance their entry into host cells (Nanbo, A. and Kawaoka, Y. Molecular mechanism of externalization of phosphatidylserine on the surface of Ebola virus particles. DNA Cell Biol., 38, 115-120 (2019);  DOI - open access).

There is currently great interest in oxidized phospholipids in animals, because of their influence on innumerable disease states. However, they are just as important in plants, in which both galactolipids and phospholipids are known to contain specific oxylipins, thanks largely to the marvels of modern mass spectrometry. The best known of these are the arabidopsides, which are formed in leaves upon wounding, but also in distant unstressed leaves so there must be some means of communication between them. A new review summarizes current knowledge (Genva, M. et al. New insights into the biosynthesis of esterified oxylipins and their involvement in plant defense and developmental mechanisms. Phytochem. Rev., 18, 343-358 (2019);  DOI.).

April 10th, 2019

There have been any number of excellent review articles on the topic of lipidomics in recent years that together cover most aspects of the techniques involved in some depth. However, if you are a complete novice to the subject where would you start? I can recommend a new review from the laboratory of Prof. Xianlin Han (Wang, J. et al. Tutorial on lipidomics. Anal. Chim. Acta, 1061, 28-41 (2019);  DOI). The text of the paper is simple, straight-forward and readable, and anything missing is covered by an extensive list of references.

This has been a good week for papers dealing with lipid methodology, and I suspect that one on the topic of oxylipins will prove to be seminal (Watrous, J.D. et al. Directed non-targeted mass spectrometry and chemical networking for discovery of eicosanoids and related oxylipins. Cell Chem. Biol., 26, 433-442 (2019);  DOI). I have yet to get hold of a copy, but from the abstract it appears that there are many more lipid mediators of this type in human plasma than have been adequately characterized to date. The authors are surely having fun exploring the chemistry of these now, especially to determine which are primary metabolites, with studies of the biological properties to follow. "Fun" is probably not the correct word, as I know how frustrating it can be to try to obtain the structures of fatty acid derivatives from minute amounts of material.

In addition, I was intrigued by a paper on derivatization reactions in the solid phase (Atapattu, S.N. and Rosenfeld, J.M. Micro scale analytical derivatizations on solid phase. Trends Anal. Chem., 113, 351-356 (2019);  DOI). There do not yet appear to be many applications to main-stream lipids as yet, but the potential is there. The same journal issue has two further reviews dealing with solid-phase methods for preparing lipid extracts.

The journal Biochimie has a special issue (Volume 159, Pages 1-122, April 2019) devoted to the topic of "Fatty acids and lipopolysaccharides from health to disease" edited by Michel Narce and Isabelle Niot. An eclectic range of topics is covered within the main subject areas.

April 3rd, 2019

It is almost 100 years since the discovery of vitamin E or tocopherol so it is appropriate to see a special journal issue devoted to review articles on the topic - "Vitamin E - Regulatory Roles" edited by A. Azzi and W.J. Whelan (IUBMB Life, Volume 71, Issue 4, Pages: 401-522, April 2019). In the early years, the function of tocopherol as an antioxidant was the focus of most research, then the signalling roles came to the fore, and now there are multiple avenues that are being explored. It seems that I am going to be rather busy now with updates to my tocopherol page, as even a cursory glance at the abstracts shows there is much that I have missed in the last year or two. In particular, I suspect that reading up on the biochemistry of the tocopherol metabolites is going to be a considerable task. For example, I was not aware until now of a publication describing how these interact with 5-lipoxygenase and thence interfere with leukotriene signalling (Pein, H. and 30 others. Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. Nat. Commun., 9, 3834 (2018);  DOI).

However, another important review is demanding my attention at the moment, and this requires updates to several of my web pages - two already (O’Donnell, V.B. et al. Enzymatically oxidized phospholipids assume center stage as essential regulators of innate immunity and cell death. Sci. Signal., 12, eaau2293 (2019);  DOI - open access). Amongst much of interest, it is suggested that the biosynthetic enzymes for free hydroxyeicosatetraenoic acids and their esterified products are colocalized and work cooperatively to the same time scale when cells are activated.

March 27th, 2019

Scottish thistleI had thought that sphingosine-1-phosphate biochemistry was largely a product of this century, so I was surprised to see the title of a new review (Saba, J.D. Fifty years of lyase and a moment of truth: sphingosine phosphate lyase from discovery to disease. J. Lipid Res., 60, 456-463 (2019);  DOI). However, it appears that the first work on this key enzyme of sphingolipid catabolism was published by Wilhelm Stoffel (who recently celebrated his 90th birthday) and colleagues in 1969. This work seems to have been ahead of its time and was largely forgotten until the late 1990s, when research was stimulated by the new findings on the biological activities of this lipid. Stoffel was also of course the key pioneer in the revealing the mechanism for the biosynthesis of sphingoid bases (see - Stoffel, W. Studies on the biosynthesis and degradation of sphingosine bases. Chem. Phys. Lipids, 5, 139-158 (1970);  DOI). Scientific historians may correct me, but I suspect that it was a further 20 years until the next important paper on the topic was published from Sarah Spiegel's laboratory (Zhang, H. et al. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J. Cell Biol., 114, 155-167 (1991);  DOI).

phosphatidylmonogalactosyldiacylglycerolNature can confound the best lipid classification schemes. For example, is the lipid illustrated (phosphatidylmonogalactosyldiacylglycerol) a glycolipid, a phospholipid, a glycophospholipid or a phosphoglycolipid (there is a difference between the last two as described here..)? In essence, it is a monogalactosyldiacylglycerol linked by a phosphate bond to phosphatidic acid. It was first described from a bacterium some years ago, and there are glucosyl equivalents, but a new paper describes undoubtedly the best characterization, including the β-D-galactopyranosyl unit and polyunsaturated acyl groups, together with its biological properties (Manzo, E. et al. Immunostimulatory phosphatidylmonogalactosyldiacylglycerols (PGDG) from the marine diatom Thalassiosira weissflogii: inspiration for a novel synthetic toll-like receptor 4 agonist. Marine Drugs, 17, 103 (2019);  DOI). It is probably best considered as a phosphoglycolipid, as it is believed to be derived biosynthetically from monogalactosyldiacylglycerols by a transphosphatidylation reaction with phosphatidylglycerol.

Two weeks ago, I suggested that a review of the connections between glycerolipid and sphingolipid biochemistry might be timely. My apologies but I have been reminded that one exists and is well worth reading (Rodriguez-Cuenca, S. et al. Sphingolipids and glycerophospholipids - The "ying and yang" of lipotoxicity in metabolic diseases. Prog. Lipid Res., 66, 14-29 (2017);  DOI).

March 20th, 2019

There have been two substantial multi-author reviews in the last six months on the health value of plant sterols and stanols in the diet (Jones, P.J.H. and 24 others. Progress and perspectives in plant sterol and plant stanol research. Nutr. Rev., 76, 725-746 (2018);  DOI.   Plat, J. and 19 others. Plant-based sterols and stanols in health and disease: 'Consequences of human development in a plant-based environment?' Prog. Lipid Res., 74, 87-102 (2019);  DOI - the latter is open access). Both support the claims for the cholesterol lowering effects of such supplements, although there is as yet no direct evidence that there is an actual reduction in the risk of heart disease. Time only will tell, but my fingers are crossed that this does indeed work, as I have been encouraging my wife to consume one of the proprietary brands for some years. The other important information that I took from the reviews is that there may be many further benefits, and I quote from the second of these publications - "ranging from its presence and function intrauterine and in breast milk towards a potential role in the development of non-alcoholic steatohepatitis, cardiovascular disease, inflammatory bowel diseases and allergic asthma." The authors consider that these additional beneficial properties may even prove to be more important than the effects upon cholesterol lowering in the long term.

Lipidomics studies are contributing substantially to our knowledge of the metabolic consequences of diseases states, including heart disease and cancer of course where lipids play an active part. It is perhaps more surprising that this can also be true of viral diseases, and a new study describes the changes in lipids brought about by the Ebola virus (Kyle, J.E. et al. Plasma lipidome reveals critical illness and recovery from human Ebola virus disease. PNAS, 116, 3919-3928 (2019);  DOI). It appears that the plasma lipidomes are profoundly altered in survivors and fatalities, and are related to the outcome and stage of the disease and recovery. Importantly, these changes in the lipidome suggest potential targets for therapy.

March 13th, 2019

A new review publication on sphingolipids is worth reading for a number of reasons, but I was intrigued by some fascinating data on how research on these lipids has expanded in recent years (Sahu, S.K. et al. Emergence of membrane sphingolipids as a potential therapeutic target. Biochimie, 158, 257-264 (2019);  DOI). The authors point out that in relation to sphingolipid metabolism their "extensive literature survey reveals a whopping 28-fold increase in the number of publications from the year 1999 onwards in comparison to papers from 1987 to 1998". I guess this has been fueled in part by the discovery of the signalling roles of lipids such as the ceramides and sphingosine-1-phosphate and in part by the development of new mass spectrometric methodologies, which have greatly simplified analysis.

It is not hard to understand why glycerolipid biochemistry and sphingolipid biochemistry are usually treated as separate subjects within lipid science. A few years ago, I was asked at a symposium whether I knew of any links between the two, and while I recalled the fact that phosphatidylcholine was an immediate precursor of sphingomyelin, my mind was a blank on other links. When I had time later, others did indeed come to mind and I began a list of additional connections, which I later incorporated into my introductory web page on sphingolipids. I continue to add to this and the most recent example is the generation of 1-O-acylceramides in skin and lipid droplets by the action of diacylglycerol acyltransferase 2 (DGAT2), a key enzyme in triacylglycerol biosynthesis. There must be more such links of which I am unaware, and I would be delighted to learn of further examples. As an alternative to my musings, perhaps someone (not me) could consider publishing a proper review on the topic!

March 6th, 2019

At first glance, the topic of prostaglandins in insects may not appear to be of special interest, but a new review has some fascinating information (Stanley, D. and Kim, Y. Prostaglandins and other eicosanoids in insects: biosynthesis and biological actions. Front. Physiol., 9, 1927 (2019);  DOI - open access). For example, it appears that there is very little arachidonic acid in insects, so the first step in prostaglandin synthesis seems to be release of linoleate from phospholipids by the action of phospholipase A2 for conversion to arachidonic acid. Then, insects do not possess cyclooxygenases but instead have a specific peroxidase termed 'peroxinectin', which produces PGH2. This is acted upon in turn by a PGE2 synthase. Thereafter, prostaglandins appear to have a similar innumerable range of functions in insects as in vertebrates, including hormone actions in the fat body and effects upon reproduction, fluid secretion, and the immune response.

I gather that it is easily possible to spend seven figure sums to purchase an NMR spectrometer these days, but I am intrigued by the possibilities for the use of low-cost bench-top instruments that do not require the use of cryogens in lipid analysis. I understand that they are relatively low field, up to about 80 Mhz, but early in my career 60Mhz was considered state of the art. These thoughts were stimulated by a paper on the analysis of phospholipids using 31P NMR with an instrument of this type (Gouilleux, B. et al. Analytical evaluation of low-field 31P NMR spectroscopy for lipid analysis. Anal. Chem., 91, 3035-3042 (2019);  DOI - open access). The results appear to show sufficient accuracy for many routine applications in food or clinical science, and certainly at least as good as alternative low-tech methods, such as thin-layer chromatography, while being much less labour intensive. I would love to drive a Ferrari, but I am content in general with my Ford Fiesta - perhaps it might be the same with NMR spectrometers?

My current moan concerning scientific publications is poor paragraph construction. I recently came across a review article in which a single paragraph extended over three pages.

February 27th, 2019

Scottish thistleHaving mentioned the need for good titles and abstracts in scientific publications in recent weeks, I should say something about the contents. I have been rather impressed by the use of colour and art work in some recent papers. When my grand-daughter was 5-6 years old, she asked me "what was life like in the black and white days?" - obviously under the impression from TV viewing that colour was a late 20th century invention. Colour in the world at large is one thing, but the world of scientific publication and presentation was largely monochromatic until well into my scientific career, although we may now take the use of colour for granted. That said, I must commend the authors of a review that has just been published for an outstanding example of the tasteful use of colour coupled with real artistic skill to complement the text and illustrate complex biological processes (Olzmann, J.A. and Carvalho, P. Dynamics and functions of lipid droplets. Nature Rev. Mol. Cell Biol., 20, 137-155 (2019);  DOI).

From time to time in this blog, I have mentioned the N-acylhomoserine lactones, which govern how many bacterial species interact with each other and with their environment. A new molecular species has just been isolated with the main fatty acid component being 2E,5Z-dodecadienoic acid. Locating double bonds close to the carboxyl group can be tricky, as they have a tendency to migrate under mild reaction conditions, so the authors had to synthesise various possibilities for comparison purposes (Ziesche, L. et al. An unprecedented medium-chain diunsaturated N-acylhomoserine lactone from marine Roseobacter group bacteria. Marine Drugs, 17, 20 (2019);  DOI). The references cited lead me to a publication that I had missed when it first appeared and contains an excellent review of the topic. It also introduced me to a whole new area (to me at least) of fatty acid biochemistry (Schulz, S. and Hötling, S. The use of the lactone motif in chemical communication. Nat. Prod. Rep., 32, 1042-1066 (2015);  DOI - open access).

February 20th, 2019

There is a new record for the most highly unsaturated natural fatty acid from a conventional source, i.e. tetratriacontadecaenoic acid or 34:10, from a fish oil supplement (Ozaki, H. et al. Basic eluent for rapid and comprehensive analysis of fatty acid isomers using reversed-phase high performance liquid chromatography/Fourier transform mass spectrometry. J. Chromatogr. A, 1585, 113-120 (2019);  DOI). The methodology used does not permit detailed determination of the structure, but that illustrated appears to be the most probable. The previous record for a normal tissue belonged to 28:8(n-3) from marine dinoflagellates, although fatty acids with an even higher degree of unsaturation have been isolated from the brains of patients with genetic impairments of peroxisome function.

34:0 fatty acid

It has long been known that aspirin inhibits the cyclooxygenase (COX) enzymes by transferring its acetyl group irreversibly to a specific serine residue, which then protrudes into the active site and obstructs the binding of arachidonate. However, COX-2 is not completely inhibited but there is shift in reaction specificity, converting the enzyme activity from that of a cyclooxygenase to a lipoxygenase, and resulting in the generation of 15(R)-hydroxy-5,8,11,13-eicosatetraenoic acid (15(R)-HETE), i.e. with the opposite chirality to that produced in the lipoxygenase reaction. Now a new publication demonstrates that some PGD2, but not PGE2, is formed also - again with the 15(R)-configuration (Giménez-Bastida, J.A. et al. Residual cyclooxygenase activity of aspirin-acetylated COX-2 forms 15R-prostaglandins that inhibit platelet aggregation. FASEB J., 33, 1033-1041 (2019);  DOI). This may contribute to the therapeutic effects of aspirin.

Two weeks ago, I commented on the need for care in preparing the title of their publications, and this is also true for the abstracts. As I will not have access to the above publication for a year, I was grateful that it had an accurate title and abstract - certainly enough for my diletante requirements. In contrast this week, I came across a paper in my literature search that claimed in the title to have discovered a novel keto fatty acid in a plant source, but with no structural information whatsoever in the abstract.

February 13th, 2019

The UK government recently announced that new funds (£30M) were being made available to universities for research into the discovery of new antibiotics, as pharmaceutical companies seem to believe that such research is not cost effective. I hope that some of this money will go to lipid biochemists, as bacterial lipopeptides are among our best hopes for success. Cyclic lipopeptides appear especially promising, and a new review discusses their biosynthesis by ribosomal and nonribosomal mechanisms as well as their therapeutic potential (Monaim, S.A.H.A. et al. Bacteria hunt bacteria through an intriguing cyclic peptide. Chemmedchem, 14, 24-51 (2019);  DOI). Although to date cyclic lipopeptides have greater antibacterial potency and greater oral bioavailability, linear lipopeptides have significant activity and cannot be neglected in that they are more accessible by chemical synthesis, so that modified forms can easily be produced in quantity (Moon, S.H. and Huang, E. Novel linear lipopeptide paenipeptin C binds to lipopolysaccharides and lipoteichoic acid and exerts bactericidal activity by the disruption of cytoplasmic membrane. BMC Microbiol., 19, 6 (2019);  DOI). The polymyxins have been around since the 1960s, but they were abandoned as systemic antibiotics because of nephrotoxicity. However, they have made something of a comeback as a drug of last resort against drug resistant Gram-negative bacterial strains, aided by the development of new derivatives. They have value also in that they damage the outer membranes of target bacteria and render them more permeable to other antibiotics (Vaara, M. Polymyxin derivatives that sensitize Gram-negative bacteria to other antibiotics. Molecules, 24, 249 (2019);  DOI).

It may seem surprising to some, but the essentiality of dietary α-linolenic acid (18:3(n-3)) was doubted by many in the lipid community until the 1970s, mainly it seems because it did not cure the dermal symptoms of EFA deficiency. The finding that docosahexaenoic acid (DHA) is necessary for optimum retinal function did not attract much attention, and the position only changed when it was observed that Greenland Eskimos had a low incidence of atherosclerotic coronary disease because of the anti-thrombotic effect of eicosapentaenoic acid in the diet. The rest as they say is history (Spector, A.A. and Kim, H.-Y. Emergence of omega-3 fatty acids in biomedical research. PLEFA, 140, 47-50 (2019);  DOI). The authors suggest that we should take note of the delay in recognizing the importance of omega-3 fatty acids if we are to avoid similar pitfalls in future.

February 6th, 2019

In my blog of January 16th, I commented briefly on the strange fact that a fatty acid present at rather low levels only in tissues, i.e. myristic or 14:0, had been adopted by natural selection almost exclusively for N-acylation of proteins. I suppose that it is advantageous to have a straight-chain saturated molecule for this purpose, as this may insert more easily into a membrane in comparison to say an unsaturated fatty acid with a kink in the 3-dimensional shape, but why 14:0? Now a new publication provides an explanation for how this occurs if not why (Soupene, E. and Kuypers, F.A. ACBD6 protein controls acyl chain availability and specificity of the N-myristoylation modification of proteins. J. Lipid Res., in press;  DOI). It is demonstrated that a protein designated 'ACBD6' supports the reaction of N-myristoyl-transferase enzymes under unfavorable substrate-limiting conditions, and prevents utilization of potentially competing species such as 12:0 or 16:0.

I have the impression that authors do not put enough thought into the titles of their papers. There is an art to it and titles that avoid abbreviations/acronyms and are brief but to the point are my favourites, such as this recent review (Lone, M.A. et al. 1-Deoxysphingolipids. Biochim. Biophys. Acta, 1864, 512-521 (2019);  DOI). The title of the paper is in fact shorter than the abbreviated name of the journal, but it tells us all we need to know. There are others who would produce a title such as "The chemistry, biochemistry and physical chemistry of 1-deoxysphingolipids with special reference to et cetera, et cetera". Whatever the title, they are fascinating lipids, not least because they have potent anti-cancer activity. You can find an introduction to the topic on this website here..

I was sorry to learn of the death of Professor Rodolfo R. Brenner from Argentina, who died last year just before his 96th birthday. I first met him in the 1960s when he visited Ralph Holman's lab, where I was a post-doc, and this encounter lead to a collaborative project and eventually a joint publication. I remember him as an enthusiastic scientist who gave great encouragement to a young man at the start of his scientific career. There is a brief memorial in PLEFA.

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Author: William W. Christie Updated: June 12th, 2019 Credits/disclaimer LipidWeb logo