Lipid Matters - Archive of Older Blogs - 2015

This Blog is an occasional series of notes on publications or other items dealing with lipid science that seem to be of particular interest to the editor Bill Christie. Inevitably, the selection is highly personal and subjective. In this web page, the blogs for 2015 are archived, while those for other years can be accessed from the foot of the current blog page.

December 30^th, 2015

Scottish thistle Phosphatidylthreonine (PtdThr) is a little known lipid first found at trace levels in brain and subsequently in a few other animal tissues and some bacterial species. It is now reported to be a major phospholipid of the protozoan parasite Toxoplasma gondii, which can infect animals and humans. As this is the holiday period, I trust readers will forgive me if I simply quote from the authors' summary - "PtdThr is made by a novel parasite-specific enzyme, PtdThr synthase, which has evolved from the widespread enzyme phosphatidylserine synthase. The study shows that PtdThr is required for asexual reproduction and virulence of the parasite in vivo, and a metabolically attenuated mutant strain of Toxoplasma lacking PtdThr can protect vaccinated mice against acute and currently incurable chronic infection. This discovery demonstrates adaptive "speciation" of PtdThr from an otherwise near-universal membrane lipid phosphatidylserine and reveals de novo PtdThr synthesis in T. gondii as a potential drug target." (Arroyo-Olarte, R.D. et al. Phosphatidylthreonine and lipid-mediated control of parasite virulence. PLoS Biol., 13, e1002288 2015; DOI). The paper is open access. I suspect that this fascinating lipid will now become more than an academic curiosity.

Formulae of phosphatidyl-L-threonine

There is an impression that the modern approach to lipid analysis is simply a matter of injecting a sample into a mass spectrometer together with appropriate standards and letting the instrument and a computer do the work - the "shotgun" technique. While this is obviously a very great over-simplification, there is increasingly an element of truth when it is applied to the analysis of the main lipid constituents of animal and plant tissues. Because of its relative simplicity, high sample throughput and cost-effectiveness, this approach has proved its value in innumerable applications. However, it fails when it comes to the analysis of minor lipids, which can be those with key biological functions. Often these are masked by major lipid components of the same molecular weight, e.g. phosphatidylglucoside by phosphatidylinositol. Combining mass spectrometry with HPLC can lead to major improvements in the number of lipid species detected, but the chromatography step can itself be challenging, especially with plant lipids where the analysis of glycosylinositolphosphoceramides presents real difficulties. A new lipidomics platform based on a single extraction step followed by a series of ultra-performance liquid chromatography separations directed to both a triple quadrupole analyzer for targeted profiling and a time-of-flight analyzer for accurate mass analysis yielded 393 molecular species within 23 different lipid classes from leaves. This is more than twice as many as the previous best. An application to drought affected plants has provided new insights into how the plant responds (Tarazona, P. et al. An enhanced plant lipidomics method based on multiplexed liquid chromatography-mass spectrometry reveals additional insights into cold- and drought-induced membrane remodelling. Plant J., 84, 621-633 (2015); DOI).

December 23^rd, 2015

There has been a long search for a universal detector for HPLC of lipids, starting with the transport-flame ionization detector, which had its good points but ultimately was a commercial failure. Then came the evaporative light-scattering detector (ELSD), which I made good use of in my own research, though I always preferred to use it with a stream-splitter as a micro-preparative tool rather than for direct quantification. In recent years, two variants on this have become available - the condensation-nucleation light-scattering detector (CNLSD), commercially known as the nano-quantity analyte detector (NQAD) and the charged-aerosol detector (CAD). So far I have seen only a handful of applications to lipid analysis with these. A new review examines the general properties of each of the three critically (Magnusson, L.E. et al. Aerosol-based detectors for liquid chromatography. J. Chromatogr. A, 1421, 68-81 (2015); DOI). The general conclusion appears to be that the CNLSD/NQAD is much the most sensitive with a linear response of at least two orders of magnitude. However, it is also responsive to impurities in the solvents, which would preclude its use with mobile phases containing ionic species as is essential for many lipid applications. Incidentally, the same issue of the journal has a useful review on detectors for gas chromatography.

I have established search parameters that I use with the Web of Science to keep myself and the literature survey pages here up to date. This means that I scan rapidly through the titles of 400 or more papers every week to select the few that I can list in my data base and the even fewer that I can take the time to read. Of course, there are innumerable new publications that simply escape my attention. One such published last year, which I have just come across, deals with what appears to be an important new class of lipids, termed "branched fatty acid esters of hydroxy fatty acids (FAHFAs)" by the authors, although they should more simply be called 'estolides' perhaps (Yore, M.M. et al. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell, 159, 318-332 (2014); DOI). I illustrate the palmitoyl ester of 9-hydroxystearate as an example.

Estolide of palmitic and 9-hydroxystearic acids

These were found in the adipose tissue of mice and more recently in eggs, and they exert their biological effects via specific receptors. Although little is yet known of their biosynthesis, it has been demonstrated that they are produced endogenously. It is also significant that they are anti-inflammatory but are not derived from essential fatty acids in contrast to the eicosanoids and docosanoids.

I wish all who read these pages a very happy Christmas and all the best for the New Year!

December 16^th, 2015

Bis(monoacylglycero)phosphate is a fascinating lipid, not least in that the stereochemistry of the glycerol moiety is the opposite of that in all other phospholipids. Much remains to be learned of the mechanism of biosynthesis, and even its structure in membranes is in doubt because of the ease with which acyl migration can occur. It is enriched in the endosomal membranes of cells in the liver and other tissues, where its stereochemistry ensures that it is not readily digested along with other lipids by the well-known phospholipases. On the other hand, there has to be a mechanism that enables turnover and a new study demonstrates that a hydrolase designated ABHD6, once thought to be mainly a monoacylglycerol lipase, is able to accomplish this with high specificity in liver (Pribasnig, M.A. et al. α/β Hydrolase domain-containing 6 (ABHD6) degrades the late endosomal/lysosomal lipid bis(monoacylglycero)phosphate. J. Biol. Chem., 290, 29869-29881 (2015); DOI).

Protein palmitoylation is an essential mechanism in cells to translocate proteins from the cytosol to membranes in a reversible manner. For many years, there was a debate as to whether this was an autocatalytic or an enzymatic process, and this was eventually settled when it was recognized that a family of protein transacylases existed that carried out the reaction; however, these enzymes were themselves palmitoylated autocatalytically. The acyltransferases of which 23 are known in humans are membrane proteins with a number of subcellular locations that span the bilayer at least four times and with a characteristic DHHC motif in a cysteine-rich domain facing the cytosol. It has now been shown that in one of these enzymes at least, the cysteine in the DHHC motif is palmitoylated autocatalytically in the presence of palmitoyl-CoA, before the palmitoyl residue is transferred from this intermediate to a target protein (Gottlieb, C.D et al. The cysteine-rich domain of the DHHC3 palmitoyltransferase is palmitoylated and contains tightly bound zinc. J. Biol. Chem., 290, 29259-29269 (2015); DOI). I have updated the figure in my web page on this topic, which I trust illustrates the mechanism.

Following my comments last week, a new study has demonstrated that obtaining a PhD can be a useful career step - see Science Daily. However, please don't get stuck on the permanent post-doc path.

December 9^th, 2015

I have commented on the lack of job opportunities for new PhDs many times in this blog, and the problem does not seem to lessen with the passing years. Too often young graduates are seen simply as a pair of inexpensive hands to progress the work of tenured scientists. However, others are aware of the problem, as a recent article in Nature testifies. The author points out that in 2013, 42% of life-science students graduated without a job commitment of any kind - a substantial increase on 10 years earlier. The author of the article suggests that one answer might be to have a new type of PhD with a greater vocational component. Perhaps! The lucky ones are those who get away from academia at the end of their PhD. Those I feel really sorry for are the scientists stuck in an unending series of short term post-doctoral positions. There needs to be a fundamental re-think, and there is encouraging evidence that some scientists looking for solutions see - rescuingbiomedicalresearch.org.

N-Palmitoylethanolamide was detected as a component of eggs more than 50 years ago and its analgesic properties were soon identified. However, interest appeared to wane for a long period until the discovery of the endocannabinoids such as anandamide resurrected interest in other amides of fatty acids. There is now a substantial body of evidence that this natural derivative of a saturated fatty acid can bring about pain relief in many circumstances, without the side effects associated with many synthetic drugs (Hesselink, J.M.K. and Kopsky, D.J. Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome. J. Pain Res., 8, 729-734 (2015); DOI). The paper is open access and as an interesting novelty there is a video abstract by the senior author. I am not aware of this fascinating lipid having been accepted officially by the FDA or any other representative body, although it is available as a non-prescription drug in the USA.

December 2^nd, 2015

Tetrahymanol is a polycylic triterpenoid and sterol surrogate first found in ciliate protozoa but subsequently in many other types of eukaryote that live under anoxic conditions, where the relevant enzymes are believed to have been introduced via gene transfer. It was also known that it occurred in two species of bacteria, where it was seen as something of an anomaly. A new publication demonstrates that it is more widespread in bacteria than had been believed, and that it is produced via a very different biosynthetic mechanism from that in eukaryotes involving a hopanoid as an intermediate (Banta, A.B. et al. A distinct pathway for tetrahymanol synthesis in bacteria. Proc. Natl. Acad. Sci. USA, 112, 13478-13483 (2015); DOI).

There is a vast literature on the biochemistry of eicosanoids and increasingly these days on docosanoids, but the oxylipins derived from linoleate are relatively neglected, although they can be more abundant in plasma than the eicosanoids. A new metabolomics study demonstrates that linoleate-derived oxylipins can account for some of the variability in the response to aspirin in terms of platelet reactivity (Ellero-Simatos, S. et al. Oxylipid profile of low-dose aspirin exposure: a pharmacometabolomics study. J. Am. Heart Assoc., 4, e002203 (2015); DOI). They certainly merit further study. Incidentally, the authors use the term 'oxylipid' as opposed to 'oxylipin'. Which is correct? A quick search on Google Scholar gave 749 uses of 'oxylipin' in 2014 and only 50 of 'oxylipid'. Personally, I prefer to use 'oxylipin' for metabolites of fatty acids and 'oxylipid' for metabolites of intact lipids - another task for the international nomenclature bodies?

Continuing on the theme of oxidized lipids, a recent issue of the journal Antioxidants and Redox Signalling has a number of review articles that I would have found useful for updating my Lipid Essentials pages on this site. However, only one of these is open access (Spickett, C.M. and Pitt, A.R. Oxidative lipidomics coming of age: advances in analysis of oxidized phospholipids in physiology and pathology. Antiox. Redox Signal., 22, 1646-1666 (2015); DOI). As this journal does not allow further access after a fixed period, I will have to forgo reading and citing these publications here.

November 25^th, 2015

Scottish thistle In a recent blog, I mentioned a review discussing the merits of saturated fatty acids in human metabolism. There is an interesting popular account of the debate on saturated fat in the diet in New Scientist. It appears to suggest that the reports that saturated fatty acids are a causal factor in heart disease can no longer be sustained. What I fail to understand is how we could have been misled for so long!

I am always fascinating by new discoveries in relation to unusual lipids, such as cholesterol 6-O-acyl-β-D-galactopyranoside and its non-acylated form, which are significant components of membranes of the tick-borne spirochete Borrelia burgdorferi, the causative agent of Lyme disease. The cholesterol comes from the animal host and its glycoside can be transferred back to the membranes of the host animal, where it may facilitate the infective process. A new study demonstrates that these glycolipids, together with free cholesterol, form raft microdomains with proteolipids in the membranes of the organism, which may permit it to sense environmental changes and adapt to the host (Toledo, A. et al. The lipid raft proteome of Borrelia burgdorferi. Proteomics, 15, 3662-3675 (2015); DOI). This is probably the first demonstration of such microdomains in a prokaryote.

Jasmonates are key plant hormones with structural similarities to the prostaglandins but derived from α-linolenic acid; they have important signalling functions in algae and higher plants, but especially for plant stress responses, growth and development. I can recommend a substantial new review of their properties that is written from a historical perspective (Wasternack, C. How jasmonates earned their laurels: past and present. J. Plant Growth Reg., 34, 761-794 (2015); DOI).

November 18^th, 2015

While I have been enjoying the sunshine of the Canary Islands over the last week, lipid science has been continuing to develop apace. Over the years, I have seen nutritional recommendations in relation to polyunsaturated fatty acids from several apparently august bodies being discredited, but rarely as thoroughly as in a new publication (Crawford, M.A. et al. The European Food Safety Authority recommendation for polyunsaturated fatty acid composition of infant formula overrules breast milk, puts infants at risk, and should be revised. PLEFA, 102-103, 1-3 (2015); DOI). It seems that the EFSA has concluded from a limited review of the literature that although docosahexaenoic acid (DHA) is required for infant formula, arachidonic acid is not "even in the presence of DHA". The authors of this rebuttal point out that arachidonic acid is not an optional drug but a ubiquitous component of the diets of newborn infants through breast milk with a myriad of essential functions. Removing it from infant formulae could have grave health implications.

Two new publications have appeared that deal with the biochemistry of cardiolipin. The first deals with the genetic disease Barth syndrome - I was deeply moved by meeting boys and young men suffering from this condition a few years ago, so any progress and increasing awareness of the condition is worthwhile (Gaspard, G.J. and McMaster, C.R. Cardiolipin metabolism and its causal role in the etiology of the inherited cardiomyopathy Barth syndrome. Chem. Phys. Lipids, 193, 1-10 (2015); DOI). The second publications deals with the ubiquitous nature of cardiolipin in Archaea, prokaryotes and eukaryotes, and its role in stress responses especially (Luevano-Martinez, L.A. and Kowaltowski, A.J. Phosphatidylglycerol-derived phospholipids have a universal, domain-crossing role in stress responses. Arch. Biochem. Biophys., 585, 90-97 (2015); DOI).

November 4^th, 2015

It is dogma among many nutritionists that saturated fatty acids are bad for us, and that we must consume as little as possible. I recall seeing palmitic acid labelled a 'poison' in one popular nutrition article some years ago. Yet there are many essential functions for saturated fatty acids, in membrane lipids, as components of proteolipids, as activators of transcription factors, and as sources of monoenoic fatty acids. I can recommend a new review that attempts to redress the balance (Legrand, P. and Rioux, V. Specific roles of saturated fatty acids: Beyond epidemiological data. Eur. J. Lipid Sci. Technol., 117, 1489-1499 (2015); DOI).

I do not forget the requirements for unsaturated fatty acids, which are required to balance the saturated components in membrane lipids as well as having innumerable metabolic functions. The essential fatty acids of the (n-6) and (n-3) families and the balance between the two is a never-ending nutritional debate. A new element has been added with the discovery of the lipid mediators derived from these fatty acids, especially the relatively recent findings on the pro-resolving docosanoids and inflammation. A new brief review offers a useful perspective on the subject (Marion-Letellier, R. et al. Polyunsaturated fatty acids and inflammation. IUBMB Life, 67, 659-667 (2015); DOI).

I have belatedly come across a series of three reviews in the Journal of Biochemistry (February issue) on the theme of "Recent Progress in Lipid Mediators". The topics covered are leukotrienes, prostaglandins and lysophosphatidic acids, and all are open access.

October 28^th, 2015

Scottish thistle The techniques and science of lipidomics have legitimized analytical chemistry as a major tool in understanding not merely the composition of lipids, but also their metabolism and functions in tissues. Increasingly, information of this kind is being obtained in relation to structures within organs and even membranes within cells by these techniques. I have just been updating my web page on sulfoglycosphingolipids, where there is now a much greater understanding of their role in the different regions of kidney in maintaining a steady pH in plasma. Similarly, lipidomic studies of different organs of more primitive organisms is providing information on relatively obscure lipids. For example, ceramide aminoethylphosphonate is a common if poorly understood lipid in marine invertebrates. A new lipidomic study has demonstrated that it is concentrated in the tentacles containing the stinging cells of jellyfish, where presumably it is able to stabilize the membranes against attach by phospholipases (Zhu, S. et al. Lipid profile in different parts of edible jellyfish Rhopilema esculentum. J. Agric. Food Chem., 63, 8283-8291 (2015); DOI).

I am fortunate in having home access to very fast broadband, which enables me to download pdf files in seconds from the websites of most of the large academic publishers. My moan this week is with many of the smaller ones, who have insufficient bandwidth so that it takes an age to access the sites and to navigate through them.

October 21^st, 2015

Because of the increasing problem with drug resistant bacteria, there is a major search underway for new antibiotics. Among the important potential sources are the bacterial lipopeptides, which can also be powerful surfactants. Lipopeptides are amphiphilic molecules that consist of short linear chains or cyclic structures of amino acids, linked to a fatty acid via ester or amide bonds or both. They are able to form pores and destabilize the membranes of bacteria. A new review summarizes their properties and applications (Ines, M. and Dhouha, G. Lipopeptide surfactants: production, recovery and pore forming capacity. Peptides, 71, 100-112 (2015); DOI).

One group that has interested me especially are the fusaricidins, because they contain the unusual fatty acid 15-guanidino-3-hydroxypentadecanoic acid, which I discussed in my blog in January this year. A new analytical study has shown that these lipopeptides in fact constitute a complex family of molecular species consisting of more than 20 variants of the basic cyclopeptide structure (Vater, J. et al. Characterization of novel fusaricidins produced by Paenibacillus polymyxa-M1 using MALDI-TOF mass spectrometry. J. Am. Soc. Mass Spectrom., 26, 1548-1558 (2015); DOI). No doubt further work will show which structures are most active biologically.

An item on the BBC website this morning discusses how scientists are thwarting the copyright attached to scientific papers together with the moral and commercial implications. I am ambivalent on the subject. As an author of a book that has been pirated (and as a former publisher), I believe that copyright should be protected. On the other hand, as a retired scientist I would like more access to online journals. There is no way that I could consider paying commercial rates to access single papers as a retiree, and I have to confess that I accessed the second of the papers cited this week on the ResearchGate website (via Google Scholar) as a proof copy. I hope that at least I am helping by drawing attention to the publication and the journal. For those journals that allow free access after a year, I am usually content to wait. Perhaps the answer would be for more journals to adopt such a policy.

October 14^th, 2015

A number of research groups operate altruistically in that they share their mass spectrometry software online. A new data base can now be added to these (Aimo, L. et al. The SwissLipids knowledgebase for lipid biology. Bioinformatics, 31, 2860-2866 (2015); DOI). I am no longer in a position to make use of this or study it in detail, so please forgive me if I simply quote from the abstract - "SwissLipids provides curated knowledge of lipid structures and metabolism which is used to generate an in silico library of feasible lipid structures. These are arranged in a hierarchical classification that links mass spectrometry analytical outputs to all possible lipid structures, metabolic reactions and enzymes. SwissLipids provides a reference namespace for lipidomic data publication, data exploration and hypothesis generation. The current version of SwissLipids includes over 244,000 known and theoretically possible lipid structures, over 800 proteins, and curated links to published knowledge from over 620 peer-reviewed publications." Thus, it appears to differ from the other databases of this type of which I am aware in that it deals with metabolic processes as well as mass spectrometry.

The shops in the UK have had their Christmas displays up for weeks. Similarly, now that we have so much publication online first, I have already started to pick up references for the Literature Survey pages here for papers dated to 2016!

October 7^th, 2015

It was something of a surprise when the neutral lipid 1,2-diacyl-sn-glycerols first were shown to be important signalling molecules back in the 1970s, as well as being components of cellular membranes and building blocks for glycerophospholipids. This is no longer news, but a current and substantial review article looks at the topic from a rather different perspective and happily it is open access (Eichmann T.O. and Lass, A. DAG tales: the multiple faces of diacylglycerol-stereochemistry, metabolism, and signaling. Cell. Mol. Life Sci., 72, 3931-3952 (2015); DOI). Their approach is to consider the stereospecificity of all the enzymes involved in diacylglycerol metabolism from lipases to kinases to demonstrate how these affect their functions. Only the sn-1,2-stereoisomer has signalling activity.

The arsenic-containing lipids (arsenolipids) in fish have been attracting great interest over the last few years. Until recently, the assumption has been that these presented no toxicity problems, because they were thought to be broken down to water-soluble metabolites, which were rapidly eliminated from the body. Then it was noted that arsenic-containing hydrocarbons were cytotoxic to human cell preparations in vitro.

Formula of 1-Dimethylarsinoylpentadecane

Now it has been shown that both arsenic-containing hydrocarbons and fatty acids are taken up readily by an intestinal model in vitro, though the fatty acids are rapidly degraded in the intestines (Meyer, S. et al. Arsenic-containing hydrocarbons and arsenic-containing fatty acids: Transfer across and presystemic metabolism in the Caco-2 intestinal barrier model. Mol. Nutr. Food Res., 59, 2044-2056 (2015); DOI). What this means for consumers of fish is uncertain, but I suspect that it will prove to be trivial at the concentrations that occur naturally otherwise effects would have been noted long before now. I will continue to enjoy fresh fish in my diet.

September 30^th, 2015

Scottish thistle Glycosyldiacylglycerols are best known as major lipids of the photosynthetic apparatus in plant. However, it appears to be less well known that mono- and digalactosyldiacylglycerols are minor lipid components of brain and nervous tissue in animals, or that glucosyldiacylglycerols with 1 to 8 glucose units are major components of the membranes of intestinal tissues. A major review on these compounds was published in 1992 in Progress in Lipid Research, yet when I undertook a citation search (ISI Web of Science) last week to see what had been published on this topic in the intervening period so that I could update the appropriate web page here, I found only 20 citations none of which appeared to advance the field. Similarly in 2001, a digalactosyldiacylglycerol was characterized from a human carcinoma and found to have distinctly different stereochemistry from the plant equivalent (see the link above for details). This paper does not appear to have been cited even once since then, so why the lack of interest? One explanation might be that a common procedure used in the preparation of glycosphingolipids for analysis involves base-catalysed methylation to remove any glycerophospholipids that might interfere; this would of course also eliminate any glycosyldiacylglycerols at the same time. Out of sight - out of mind.

The exception is seminolipid, i.e., a glycerolipid analogue of cerebroside sulfate that also has parallels with the plant sulfolipid. This is an important constituent of male reproductive tissues but is also found in many other tissues. Unusually for a lipid from sperm and testis, it is highly saturated and consists largely of the 17:0-alkyl-16:0-acyl species. This lipid does seem to get the attention it merits.

September 23^rd, 2015

Gangliosides are fascinating lipids that are essential for the development of the brain and nervous tissues. They have always been a challenge to lipid analysts, however, partly because of their intrinsic complexity and partly because of their high polarity. A valuable new publication describes the analytical problems, and suggests a comprehensive route to detailed analysis (Masson, E.A.Y. et al. Apprehending ganglioside diversity: a comprehensive methodological approach. J. Lipid Res., 56, 1821-1835 (2015); DOI). One aspect I found especially interesting is that the favoured method for separating individual ganglioside types is still high-performance thin-layer chromatography, not ultra-high-performance liquid chromatography or shotgun mass spectrometry, which are now so widely used for other aspects of the analysis of complex lipids. Sometimes the "old-fashioned low-tech" methods are the best.

Incidentally, in revising and updating my web page on gangliosides here, I came across an excellent article on their structures and function by a well-known expert in the field that I had missed when it was first published (Kolter, T. Ganglioside biochemistry. ISRN Biochemistry, 2012, 506160 (36 pages) (2012); DOI). It has the additional virtue of being open access.

We are used to the merits and demerits of omega-3 fatty acids being discussed and argued over in relation to human health by everyone from serious scientists to media charlatans to the point where it is impossible for more objective observers to be sure of the true situation. One aspect I had never considered is the value of omega-3 fatty acids to the health of the oceans. It appears that copepods, minute creatures related to crabs, like all animals require a source of essential fatty acids and especially omega-3s, which they acquire by consuming marine algae. In turn, the copepods are a major source of food for fish larvae, so a healthy population leads to lots of fish who also require omega-3s. In addition, it is noted that the marine algae take up atmospheric carbon, a proportion of which is locked up permanently as dead organisms and their excreta fall to the ocean floor. You can find a longer version of the story together with a link to the original research in Science Daily.

September 16^th, 2015

When I do my weekly literature search, it is a common occurrence to find a new lipid described, usually from some obscure organism. It is virtually unheard of to find a new important membrane lipid in an animal or higher plant context. Nonetheless, this happened two years ago when glucuronosyldiacylglycerol (a conjugate of diacylglycerol with glucuronic acid) was found in the model plant Arabidopsis thaliana during phosphate deprivation. It accompanied the plant sulfolipid sulfoquinovosyldiacylglycerol (SQDG) to replace the phospholipids. The likelihood was that the new lipid was produced by the SQDG synthase. In a new publication from the same laboratory, these findings have now been confirmed and extended (Okazaki, Y. et al. Induced accumulation of glucuronosyldiacylglycerol in tomato and soybean under phosphorus deprivation. Physiologia Plantarum, 155, 33-42 (2015); DOI). It is now evident that the new lipid occurs in a wide range of plant species under normal growth conditions, but it increases appreciably in concentration when phosphate is limiting, presumably to help to supply a need for anionic lipids in the chloroplast membranes.

Forgive me if I point out that it is easy to incorporate this new information quickly into a relevant webpage here, long before it appears in major review articles or text books - a major virtue of the WWW.

Biosynthesis of 4,7,10,13,16,19-docosahexaenoic acid (22:6(n‑3) has long been though to proceed by chain-elongation of 22:5(n‑3) to 24:5(n‑3), desaturation to 24:6(n‑3) by a Δ6 desaturase, followed by beta-oxidation to 22:6(n‑3), i.e., by the 'Sprecher pathway' named after Howard Sprecher, who was briefly a colleague of mine at the Hormel Institute in 1964. Now new research has shown that 22:5(n‑3) can be desaturated directly to 22:6(n‑3) by a Δ4 desaturase produced by the FADS2 gene in human cells (Park, H.G. et al. The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n‑3 docosahexaenoic acid and n‑6 docosapentaenoic acid in human cells. FASEB J., 29, 3911-3919 (2015); DOI). Regretfully, I will have to wait for a year after the print version of the paper appears before I can read it.

This contrasts with the journal Free Radical Research (Volume 49, Issue 7, 2015), which has just published a special issue on "Recent progress in lipid peroxidation based on novel approaches" (H. Yin, E. Niki and K. Uchida), which looks interesting but which I will never be able to read directly as they don't have an enlightened policy in relation to access.

September 9^th, 2015

What is the most abundant lipid on Earth? Over the years, I have seen suggestions of at least four different lipid classes that might hold this title. Amongst living organism, two different plant lipids have been suggested. The first lipid class is the galactosyldiacylglycerols, which are present in all chloroplasts of green leaves of higher plants as well as in lower photosynthetic organisms. The second is the layer of wax that covers the leaves and often the shoots of plants. How do we decide between these two? The third class to come into the reckoning is the ether lipids of the Archaea. It is claimed that these organisms make up 20% of the total biomass in the oceans, so that will add up to a lot of lipid, but what about the other 80%? If in addition to living organisms, we consider the lipids deposited in sediments then the total of archaeal lipids increases very substantially as their structures remain stable over geological time scales. Similarly, I have seen suggestions that hopanoids are also chemically stable and accumulate in sediments, and they are obviously favoured as world champions by experts in this particular field. On the other hand, if we are going to consider lipids in sediments, we might have to consider petroleum deposits, although in this instance it may be harder to determine the original lipid precursors. I will let others argue over the answer to the question I posed at the beginning.

September 2^nd, 2015

It has been fairly evident from small studies over some years that dietary fish oil supplements do not improve cognitive ability in the elderly, and this has now been confirmed by a major new study that has been widely cited in the scientific press and in popular news media. Unfortunately, the message that this refers only to the elderly, while there is a body of evidence from other studies that there are significant improvements for the very young, has been lost in subsequent discussions. I watched a debate on the BBC News last week in which the participants had read the popular reports and were lamenting the fact that they had been made to take fish oil capsules by their parents in their youth. In fact they were lucky to get it in capsule form - my generation were given cod liver oil by the spoonful (as a source of vitamin D rather than of omega-3 fatty acids). Of course, there are many other good reasons to continue taking omega-3 fatty acid supplements in adulthood. If in doubt, check out the most recent PUFA Newsletter

Phosphatidylglucoside is a novel lipid in many ways, and for example its glycerolipid component more resembles a ceramide than a phospholipid in its fatty acid composition and physical properties. A new publication demonstrates that lysophosphatidylglucoside, i.e., with one fatty acid constituent, has distinctive biological activity in guiding the specific location of axons in the developing spinal cord, while mediating glia-neuron communication. The mechanism involves a G protein-coupled receptor GPR55, which was first identified as a receptor for lysophosphatidylinositol but is now determined to have a much higher affinity for lysophosphatidylglucoside (Guy, A.T. et al. Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord. Science, 349, 974-977 (2015); DOI).

August 26^th, 2015

Scottish thistle Two special journal issues devoted to lipids have come to my attention, one a little belatedly. Biochimica et Biophysica Acta (BBA) - Biomembranes (Volume 1848, Issue 9, Pages 1727-1954, September 2015) is devoted to the topic of "Lipid-protein interactions" (edited by Amitabha Chattopadhyay and Jean-Marie Ruysschaert). One article that interested me especially is devoted to cholesterol metabolism in cells and is open access.

Formula of 13-cysteinylglycinyl,14-hydroxy-docosahexaenoic acid The second journal is Seminars in Immunology (Volume 27, Issue 3, 145-234, May 2015), which covers the topic of "Resolution of inflammation: New mechanisms in patho-physiology open opportunities for pharmacology" (edited by Mauro Perretti). This appears to be the most active and promising topic at present in relation to eicosanoid/docosanoid biochemistry, with the group lead by Professor Charles N. Serhan at the forefront. They do indeed contribute a substantial review to this journal issue, but only mention briefly a fascinating new range of metabolites. Last year the group published a paper describing novel sulfido-conjugates derived from epoxy-maresin (Dalli, J. et al. Identification of 14-series sulfido-conjugated mediators that promote resolution of infection and organ protection. PNAS, 111, E4753-E4761 (2014); DOI). These compounds, such as 13-cysteinylglycinyl,14-hydroxy-docosahexaenoic acid illustrated bear more than a passing resemblance to the pro-inflammatory cysteinyl-leukotrienes, although their biological effects are very different. At nanomolar concentrations, the new metabolites were shown to resolve E. coli infections, and in general they constitute a novel mechanism of chemical signalling that contains infections, stimulates resolution of inflammation, and promotes the restoration of function in human tissues and those of experimental animals. Similarly, in a paper published this year, the group show that protectins and resolvins produce related sulfido-conjugates that stimulated human macrophages and limited the effects of bacterial infections in a dose-dependent manner (Dalli, J. et al. Novel proresolving and tissue-regenerative resolvin and protectin sulfido-conjugated pathways. FASEB J., 29, 2120-2136 (2015); DOI). Unfortunately, I will have to wait a year until access to the latter paper is opened.

August 19^th, 2015

Lipid droplets in tissues were once considered to be boring lumps of fat of little interest to anyone, but now it is recognized that they are dynamic organelles with numerous enzymes attached and a plethora of biological functions. Not only do they act as a reservoir of fatty acids for energy, protecting cells from lipotoxicity, but they also store a number of biologically active lipids to be sent to other tissues under appropriate stimulation. They regulate appetite and energy metabolism through release of adipokines, but they also are the source of hormones, secondary messengers and vitamins. Not surprisingly many proteins in the surrounding monolayer function in lipid metabolism, but others are involved in interorgan communication, development and immunity. A new review summarises the current state of play in relation to those in animal tissues (Hashemi, H.F. and Goodman, J.M. The life cycle of lipid droplets. Curr. Opinion Cell Biol., 33, 119-124 (2015); (DOI).

While lipid droplets in animal tissues have received most study for obvious reasons, those present in plants are equally important to life on earth and a further review discusses lipid droplets or plastoglobules in the photosynthetic apparatus of plants (Rottet, S., Besagni, C. and Kessler, F. The role of plastoglobules in thylakoid lipid remodeling during plant development. Biochim. Biophys. Acta, Bioenergetics, 1847, 889-899 (2015); (DOI). They appear to function in innumerable aspects of thylakoid function, and the attached proteins "act in metabolite synthesis, repair and disposal under changing environmental conditions and developmental stages".

August 12^th, 2015

Sulfoquinovosyl diacylglycerol, the plant sulfolipid, is a glycolipid characteristic of photosynthetic organisms, including higher plants, algae, chloromonads and cyanobacteria. It is a key component of the photosynthetic apparatus and as such is essential to the continuance of life on earth. It does not occur in animal tissues, although there is a lipid with some structural similarities - seminolipid found in reproductive and some nervous tissues. I was therefore intrigued by a report (open access) that it selectively inhibits acute lymphoblastic leukemia cells in vivo in a mouse model. The authors suggest that it may partly replace some of the drugs used in chemotherapy to minimize side effects (Jain, C.K. et al. Sulfonoquinovosyl diacylglyceride selectively targets acute lymphoblastic leukemia cells and exerts potent anti-leukemic effects in vivo. Scientific Reports, 5, 12082 (2015); DOI). Note that the authors and journal cannot spell the name of the active compound (sulfoquinovosyl diacylglycerol NOT sulfonoquinovosyl diacylglyceride).

A correspondent has brought to my attention an interesting news item in the journal Chemistry and Industry (August issue, page 13). The pharmaceutical company Thetis is producing amide derivatives of omega-3 fatty acids to transform the latter into free flowing powders that are claimed to increase the bioavailability of the fatty acids. From the company standpoint, these new formulations are patentable and less likely to be copied by competitors. One new drug under test is an ionic compound derived from docosapentaenoic acid (22:5(n-3)), which shows promise to boost the LDL-cholesterol lowering ability of statins, while reducing any side effects. Of course, fatty acid amides can have biological effects in their own right (cf., the endocannabinoids), and these will have to be checked if the new drugs are to receive regulatory approval.

August 5^th, 2015

Of all the lipids that might be named as a signalling molecule, the last I would have expected might be the C₁₈ saturated fatty acid - stearic acid. Yet this has just happened in a new publication in Nature in which stearic acid and human transferrin receptor 1 are shown to be regulators of mitochondrial function (Senyilmaz, D. et al. Regulation of mitochondrial morphology and function by stearoylation of TFR1. Nature, Online; DOI). A novel signalling pathway has been demonstrated whereby C18:0 stearoylates TFR1, i.e., it adds covalently to the protein by a mechanism analogous to palmitoylation. This inhibits its signalling actions, leading eventually to the promotion of mitochondrial fusion and function. According to the authors "This work identifies the metabolite C18:0 as a signalling molecule regulating mitochondrial function in response to diet".

Two weeks ago, I discussed the importance of gangliosides and recommended a review that discussed their importance in brain development. By coincidence, a second review has just been published on the same topic (Schengrund, C.L. Gangliosides: glycosphingolipids essential for normal neural development and function. Trends Biochem. Sci., 40, 397-406 (2015); DOI). I have always found it fascinating that ganglioside biosynthesis in the human brain differs in a significant way from that of all other animals including the great apes. Indeed, as far as I am aware, this is the only major metabolic distinction from apes. The same issue of the journal carries a second review on aspects of ganglioside biochemistry and function (Ledeen, R.W. and Wu, G.S. The multi-tasked life of GM1 ganglioside, a true factotum of nature. Trends Biochem. Sci., 40, 407-418 (2015); DOI). GM1 is one of the simplest of the gangliosides in structure, yet it has a wide range of functions through binding via specific proteins with glycolipid-binding domains, which are located in raft domains of membranes. To quote from the abstract, it modulates "mechanisms such as ion transport, neuronal differentiation, G protein-coupled receptors (GPCRs), immune system reactivities, and neuroprotective signalling".

July 29^th, 2015

Scottish thistle A few years ago, I had to have surgery to for cataracts in my eyes. This involved removing the natural lens of the eye and replacing it with one of plastic. The procedure was quick and relatively safe, but any operation is a cause for concern. I was expecting only damage limitation, but the effects were wonderful - after 60 years I no longer needed to wear glasses other than for reading, and colours were brighter and 3D vision was sharper. Three cheers for our free National Health Service. A new publication now suggests that there is hope that surgery may not be required in future thanks to a lipid - lanosterol (Zhao, L. et al. Lanosterol reverses protein aggregation in cataracts. Letter to Nature published online; DOI). The lens of the human eye is comprised largely of crystalline proteins assembled into a highly ordered state, which is disrupted during cataract formation with formation of protein aggregates. Treatment with lanosterol, an important intermediate in cholesterol biosynthesis, reduced cataract severity appreciably both in vitro and in vivo in experimental animals. The authors state "Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.

On the other hand, not all the news on the sterol front is good. There is a school of thought that considers oxidized cholesterol formed as a consequence of oxidative stress in the brain to be an important factor in inflammation. This in turn may be highly relevant to the development of Alzheimer's disease. A new review (open access) summarises the evidence (Gamba, P. et al. Oxidized cholesterol as the driving force behind the development of Alzheimer's disease. Front. Aging Neurosci., 7, 119 (2015); DOI).

Continuing the theme of sterols, two issues of journals have recently been devoted to sterol topics. Thus, Steroids (Vol. 99, Part B, Pages 117-298, July 2015) is devoted to the topic of "Oxysterols and related sterols: chemical, biochemical and biological aspects" (edited by Iuliano, L. and others). Similarly, the Journal of AOAC International (Volume 98, May/June) contains a number of articles under the theme of "Safety, health, and methodological aspects of plant sterols and stanols". Judging from the list of papers in press, the journal Lipids is also planning a special issue on sterols.

July 22^nd, 2015

Gangliosides are crucial lipid components of animal systems, although their study has become a separate subject from the mainstream as they are most unlipid-like in most of their physical properties. For example, in the Folch extraction procedure, they partition into the aqueous phase with the non-lipids rather than into the organic phase. In my nearly 50 years of research, I have always discarded the aqueous layer and thrown them away! They are especially important in neuronal cell membranes and it is acknowledged that they play a critical role in neuronal and brain development. According to a new review article, "they are functionally involved in neurotransmission and are thought to support the formation and stabilization of functional synapses and neural circuits required as the structural basis of memory and learning. Available evidence suggests that dietary gangliosides may impact positively on cognitive functions, particularly in the early postnatal period when the brain is still growing" (Palmano, K. et al. The role of gangliosides in neurodevelopment. Nutrients, 7, 3891-3913 (2015); DOI). The review is open access.

New functions for minor lipid components are now reported every week, so that it much be difficult for newcomers to the subject to realize how surprising it was for most of us when it was first revealed that a lipid we had never heard of previously, lysophosphatidic acid, had essential messenger functions. I first came across it when a correspondent wrote to ask how best to analyse it, since it had just been shown to be implicated in ovarian cancer. I had no idea how to help. Two new studies highlighted in Science Daily illustrate the importance of this lipid to neurotransmission and to myelin formation.

July 15^th, 2015

The website Science Daily provides a link to an interesting new development in the science of brown fat that has the potential to lead to highly significant improvements in the treatment of type 1 diabetes. It is reported that a transplant of embryonic brown fat reversed the disease and restored glucose tolerance to normal in non-obese diabetic mice (in 53 percent of the study sample) without the use of insulin, and that such transplantation before onset could delay or prevent the disease altogether.

As I mention in my last blog, I keep an eye out for anything that might alleviate the symptoms of cognitive decline with aging. Unfortunately, a new meta-analysis seems to demonstrate that omega-3 fatty acids are not the answer except in rare circumstances (Cooper, R.E. et al. Omega-3 polyunsaturated fatty acid supplementation and cognition: A systematic review and meta-analysis. J. Psychopharm., 29, 753-763 (2015); DOI). I'll keep taking my fish oil tablets, in the expectation that they have other beneficial functions.

I try to keep clear of the thorny subject of fatty acids in nutrition, as I have the impression that the topic is subject to constant re-assessment. This view is confirmed by a fascinating report of a debate by recognized experts, who appear to cast doubt on the dogma on whether reducing the intake of saturated fatty acid lowers the risk of coronary heart disease (Nettleton, J.A. et al. ISSFAL 2014 Debate: it is time to update saturated fat recommendations. Annals Nutr. Metab., 66, 104-108 (2015); DOI). One problem seems to be what the replacement for saturated fat should be.

The journal Analytical and Bioanalytical Chemistry (Volume 407, Issue 17, pp. 4971-5239, July 2015) is largely devoted to the topic of 'Lipidomics' (guest editor - Michal Holčapek). As might be expected most of the substantial number of articles deal with mass spectrometry of lipids, and I note that many of the important scientists in this area have provided contributions. Most of these reviews will be listed in my next monthly literature survey.

July 8^th, 2015

Heinrich Otto Wieland (1877-1957) is one of the great lipid scientists, who was awarded the 1927 Nobel Prize in Chemistry for his research into the bile acids. His achievements were extraordinary considering that he did not have access to any of the chromatographic and spectroscopic techniques we take for granted nowadays. He is back in the news after his Nobel medal was recently auctioned, and it is evident that he was also a great humanitarian. I have been entranced by a newspaper account - not of his science but of his life, as he was a dedicated and active anti-Nazi, who did not shirk assisting Jewish students or attempting to protect co-workers, even during the war years. The account in The Guardian is well worth reading. If you are interested in a relatively accessible account of the history of bile acid research, I can recommend a recent article in the Journal of Lipid Research.

I have reached an age when I read anything that might be relevant to delaying the onset of dementia or Alzheimer's disease with great interest. There is a popular account, with a link to the original paper, of work suggesting that omega-3 supplements and antioxidants may help with preclinical Alzheimer's disease in Science Daily. It is suggested that clinical trials should be undertaken for people with mild impairment.

I have no intention of commenting on political matters here, but innumerable holidays in Greece over the years have left me with nothing but happy memories of the country and its people. Everyone is apparently suffering real hardship and to add to the tribulations of scientists there, it seems they have been unable to continue their subscription to online journals as well as losing research funding.

July 1^st, 2015

I have just been revising my web page on phosphatidylinositol mainly in the light of two recent papers from the same laboratory (where I have to make do with the abstracts as I don't have access to the full publications). A distinctive feature of the mammalian lipid is that it consists largely of a single molecular species with stearic acid in position 1 and arachidonic in position 2. This is important for a number of reasons, not least because this is the primary source of arachidonic acid for eicosanoid production and also of specific diacylglycerols with messenger functions. It has long been assumed that the final composition is attained by the 'Land's cycle', the process of partial hydrolysis and re-acylation that leads to remodelling of the fatty acids compositions in each position. While this process probably does occur, it seems that a more important pathway and the key to the specificity is the use of a specific cytidine diphosphate diacylglycerol synthase (CDS2), which generates preferentially the precursor cytidine diphosphate diacylglycerol as the 1-stearoyl-2-arachidonoyl species (D'Souza, K. et al. Distinct properties of the two isoforms of CDP-diacylglycerol synthase. Biochemistry, 53, 7358-7367 (2014); DOI). In contrast, the next step in which a phosphatidylinositol synthase catalyses the reaction of CDP-diacylglycerol with inositol exhibits no specificity for particular molecular species (D'Souza, K. and Epand, R.M. The phosphatidylinositol synthase-catalyzed formation of phosphatidylinositol does not exhibit acyl chain specificity. Biochemistry, 54, 1151-1153 (2015); DOI).

Incidentally, I have found it very difficult to find information on the amount and composition of cytidine diphosphate diacylglycerol as it occurs naturally in tissues. It seems that the natural levels must be too low to by detected in modern lipidomic studies. In my web page on this lipid, I had to cite data from a paper published in 1976.

June 24^th, 2015

Scottish thistle The FDA has decided that artificial trans fat must be removed from the food supply in the USA over the next three years because of the health concerns, which now appear to be well established. However, all trans fat will not be eliminated because that which occurs naturally in meat and dairy products will still be permitted. FDA also agree that the small amount produced during commercial refining can remain. The change has come about from the campaigning of one very special scientist - Professor Fred Kummerow, who will be 101 this year. He tells his own story on this link...

Incidentally, the great French lipid chemist Chevreul also made it past his 100th birthday, and there is an account of his life and a picture of him at work in his laboratory in his hundredth year here..

There is an important thematic minireview series in the June 19th issue of the Journal of Biological Chemistry on the topic of "Novel Bioactive Sphingolipids" (edited by Alfred H. Merrill, Jr. and George M. Carman). In addition to an introductory commentary by the editors, there are three highly topical reviews, which deal with galactosylceramides, dihydroceramides and 1-deoxysphingolipids, respectively. The last of these is open access. Some aspects of sphingolipid biochemistry have been reviewed to death in recent years - but not these topics!

The May issue of the journal Advances in Nutrition has a number of review articles under the heading of "Oils: Where Food Function Meets Health". I will have to wait a year until access is opened to all. The August issue of Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids is devoted to the topic of "Brain Lipids" (edited by Anthony H. Futerman).

June 17^th, 2015

I am always fascinated by new lipid structures and new functions of lipids, and a recent publication certainly meets both of these criteria. A group of signalling molecules, which unsurprisingly are now termed 'copepodamides', are released into the marine environment by copepods (zooplankton). These are polar lipaminoacids that connect taurine via an amide linkage to isoprenoid fatty acid conjugates of varying compositions.

copepodamide

Minute concentrations of this unique lipid stimulate bloom-forming dinoflagellates (phytoplankton) to produce large amounts of paralytic shellfish toxins, which are presumed to be a defense response (Selander, E. et al. Predator lipids induce paralytic shellfish toxins in bloom-forming algae. Proc. Natl. Acad. Sci. USA, 112, 6395-6400 (2015); DOI).

It has long been known that ganglioside GM1 binds to amyloid protein in brain, a fundamental event in the pathological process of Alzheimer's disease. It seems that there is growing evidence that the lipid is an endogenous seed for amyloid fibril formation in the diseased brain. A new review summarises the evidence (Yanagisawa, K. GM1 ganglioside and Alzheimer's disease. Glycoconjugate J., 32, 87-91 (2015); DOI). Ganglioside GM1 has unique molecular characteristics that enable it to alter conformation in a manner that accelerates accelerate assembly of the amyloid protein complexes. A second review in the same issue of this journal discusses these special physical properties. It is hoped that an increased understanding of this process will lead to the development of new drugs and therapies.

June 10^th, 2015

I am back at my desk and trying to catch up with the world of lipids, although I am missing the sunshine of Gran Canaria sadly. While I have been relaxing, an interesting review has appeared on phosphatidylserine (Glade, M.J. and Smith, K. Phosphatidylserine and the human brain. Nutrition, 31, 781-86 (2015); DOI). There is a useful discussion of the biological function of this lipid in brain, but I was concerned about a statement in the abstract that "Exogenous phosphatidylserine (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells". Within the article a letter to the FDA in 2003 is cited as indicating that the FDA support this contention, although I was aware of a publication from 2006 that disputed this. It has sent me back to Google where I found a detailed communication from 2004 refuting the earlier letter. It appears that FDA actually doubts the potential benefits of PS supplementation (www.fda.gov) - "Very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of dementia in the elderly. FDA concludes that there is little scientific evidence supporting this claim." There is a similar statement regarding Alzheimer's disease. The FDA site now has 700 listings that refer to phosphatidylserine, and regretfully I don't have the time to research this more fully. I would be interested in knowing whether there has been a recent re-evaluation.

Two special journal issues with a lipid theme have come to my attention, i.e., on "Lysophospholipids in Biology" in Experimental Cell Research (Volume 333, Issue 2, Pages 165-326 (2015)), and on "Molecular Medicine of Sphingolipids" in Biological Chemistry (Volume 396, Issue 6-7 (Jun 2015)). I don't have access to the latter, but two of its reviews are open access.

May 20^th, 2015

Scottish thistle I find it a refreshing change to find a paper that tells us what is not known about a subject rather than what we do know. For example, it is apparent that anaerobic bacteria must synthesise ether lipids using a different mechanism from that in animals, but quite what that it is uncertain though some suggestions are offered here (Grossi, V. et al. Mono- and dialkyl glycerol ether lipids in anaerobic bacteria: biosynthetic insights from the mesophilic sulfate reducer Desulfatibacillum alkenivorans PF2803(T). Appl. Environm. Microbiol., 81, 3157-3168 (2015); DOI). This leads me to my bargain of the week. A substantial review on microbial lipids has just appeared on line and open access ahead of formal publication (Sohlenkamp , C. and Geiger, O. Bacterial membrane lipids: diversity in structures and pathways. FEMS Microbiol Rev., in press; DOI). I am sure that I will be consulting it frequently over the coming months as I update my web pages here.

The omega-3 bandwagon rolls on. I don't have access to many of the original publications in nutritional journals, but the more striking findings tend to be reported in the digital scientific press. There has been a great deal of work that appears to show beneficial effects of omega-3 fatty acids on behaviour and intelligence in young children. While I tend to be sceptical of many research findings in this area, this seems to have a solid ground. Now a new study follows up what happened to children who participated in such a study at age three - "At 11 years, the participants showed a marked improvement in brain function as measured by EEG, as compared to the non participants. At 23, they showed a 34 percent reduction in criminal behaviour". My generation were force fed cod-liver oil as children - not for the omega-3 content but for its vitamin D. It is not for me to say whether there were other beneficial side effects.

More relevant to my present age and health is a new study in guinea pigs, which shows that omega-3 fatty acids prevent or slow progression of osteoarthritis. I regret that I have been complacent about my own omega-3 intake as I like fish and consume as much as I can. However, I now take regular fish oil supplements, though whether they are doing any good only time will tell

May 13^th, 2015

A guest editorial (open access) caught my eye this week (Ogawa, J. New lipid science in our inner ecosystem. Eur. J. Lipid Sci. Technol., 117, 577-578 (2015); DOI). The titular 'ecosystem' is in fact the human intestines, which the author points out contains more microbial cells than there are cells in the tissues per se. The microorganisms have considerable potential to influence the lipid metabolism in the body of their host, and they do indeed do so by hydrogenation of fatty acids and by converting dietary linoleic acid to various oxygenated derivatives with distinctive biological properties.

There has been a resurgence of interest in bile acids in recent years. It was long thought that there only significant function was to act as emulsifiers to aid fat digestion. This is of course important, but it is now recognized that via the enterohepatic circulation, they are returned to the liver to exert important signalling functions via specific receptors. They control their own synthesis and export, but they also influence a host of other metabolic pathways where a new review suggests there is considerable pharmacological potential for intervention as a therapeutic strategy for liver and metabolic diseases (Mazuy, C. et al. Nuclear bile acid signaling through the farnesoid X receptor. Cell. Mol. Life Sci., 72, 1631-1650 (2015); DOI).

Science Daily has just covered a story that dietary fish oils alleviate the symptoms of diabetic neuropathy in mice and can restore the condition of nerves damaged by the disease (I don't have access to the original publication). It is suggested that the resolvins may be the active agents. Regretfully, many studies of this kind, which work with genetically similar animals, often fail with mixed human populations, but hope springs eternal. At least, fish oil supplements are safe and free from side effects.

May 6^th, 2015

I tend to steer clear of nutritional aspects of lipid science in this blog. It often seems to me that as soon as a publication appears describing nutritional findings, another comes out with contradictory results or that criticises the design of the experiment in some way. These days, I rarely have time to consult the original literature, but rely on accounts in the popular scientific press, such as New Scientist or Science Daily. Perhaps that is my mistake. My favourite news site for lipid nutritional matters, which seems to hit the right balance for a general scientific audience, is the Fats of Life. I look forward to receiving their regular newsletters, the most recent of which arrived the other day.

One of the most unusual lipids is bis(monoacylglycero)phosphate (or 'lysobisphosphatidic acid'). It differs from other glycerophospholipids in its stereochemistry in that the phosphodiester moiety is linked only to positions sn-1 and sn-1' of glycerol, rather than to positions sn-3 and sn-3'. Early NMR experiments suggested that the fatty acids were in the primary positions, but subsequent studies suggest that this may have been a result of acyl migration during extraction and analysis. Biosynthetic considerations have lead to the hypothesis that the fatty acids are in fact in the 2,2' positions, although much remains to be learned of the biosynthetic mechanisms. The lipid is a key component of lysosomes, where the odd stereochemistry may hinder self digestion of the membranes. It is well known that the lipid tends to accumulate, probably as a secondary effect, in lysosomal storage diseases. A new publication finds that it accumulates in brain tissue in gangliosidoses resulting from inherited deficiencies in β-galactosidase or β-hexosaminidase (Akgoc, Z. et al. Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses. J. Lipid Res., 56, 1006-1013 (2015); DOI). If you would like a more general review, I can recommend Schulze, H. and Sandhoff, K. (Sphingolipids and lysosomal pathologies. Biochim. Biophys. Acta, 1841, 799-810 (2014); DOI).

April 29^th, 2015

Scottish thistle In recent weeks, I have highlighted reviews dealing with the membrane microdomains known as rafts in plants and bacteria. Now a new article suggests that they do not exist (Sevcsik, E. et al. GPI-anchored proteins do not reside in ordered domains in the live cell plasma membrane. Nature Commun., 6, 6969 (2015); DOI). As I don't have access to this journal, I am reliant upon a report in Science Daily News. It appears that the authors use advanced microscopy methods, first fixing specific proteins on a structured surface and then studying the movement of lipids around them. I will be an interested spectator when the proponents of rafts react.

The journal Apoptosis (Volume 20, Issue 5, May 2015) is a special issue devoted to the topic of "The role of sphingolipids and lipid rafts in determining cell fate" (edited by Walter Malorni and Paola Matarrese). There are a number of review articles in this that look interesting (two are open access), and which I will have to read before updating my web pages here. I am glad that the editors were not informed in advance that rafts are a myth.

A new article available in manuscript form ahead of publication in the Journal of Lipid Research also looks as if it is going to stir things up (Munroe, W.H et al. Excessive centrifugal fields damage high-density lipoprotein. J. Lipid Res., DOI. First Published on April 24, 2015). It suggests that the methodology that has been employed for the study of lipoproteins for 40 years is flawed and can lead to the shedding of proteins from the HDL fraction.

April 22^nd, 2015

Some weeks ago I suggested that we need to know more about the biologically active hydroxyoctadecadienoic acid (HODE) isomers in human tissues, as they are vastly more abundant in human tissues than the eicosanoids, for example, which receive so much attention. A new review in an open access journal discusses their chemistry and potential role as biomarkers of disease (Yoshida, Y. et al. Chemistry of lipid peroxidation products and their use as biomarkers in early detection of diseases. J. Oleo Sci., 64, 347-356 (2015); DOI).

The journal Plant Cell Reports has released a special issue (Volume 34, Issue 4, April 2015) on the topic of "Plant Lipid Biology and Biotechnology". The guest editor is Mi Chung Suh, who contributes a timely review of plant surface waxes, while I was especially interested in two reviews on suberin polymers, especially one from Isabel Molina's lab.

One of my favourite websites, Science Daily News, carried and interesting story on the production of novel polyurethanes made from plant oils. I don't have access to their source material, but it appears that they convert unsaturated fatty acids to polyols then react with ricinoleic acid derivatives from castor oil. They can vary the stiffness of the polymer by changing the nature of the vegetable oil.

April 15^th, 2015

The topic of the oxygenated metabolites of the long-chain polyunsaturated fatty acids of the (n-3) family, which have been termed 'protectins, resolvins and maresins' or collectively the 'specialized pro-resolving mediators' or SPMs, has become increasingly important in recent years. Although the main focus has been on how they are produced locally to terminate inflammation, it is now recognized that they also reach the circulation and are found in human peripheral blood, suggesting that they may act as anti-inflammatory signals in tissues other than those in which they originate. For example, significant levels of resolvins together with lipoxins have been found in human breast milk and in animal placenta, so it is possible that they may have regulatory functions in normal physiological development as well as in pathophysiological processes. These compounds will always be associated with Professor C.N. Serhan, whose group has produced a number of interesting review articles to summarize current knowledge in recent years. However, their most recent magnum opus has the considerable virtue of being open access, and as such I have no hesitation in recommending it (Serhan, C.N. et al. Lipid mediators in the resolution of inflammation. Cold Spring Harbor Persp. Biol., 7, a016311 (2015); DOI).

In last week's blog, I discussed a review of the existence and function of raft domains in plants. Now, a new review suggests that there is evidence for functionally related microdomains in bacteria, which "organize many signal transduction, protein secretion, and transport processes". Of course, bacteria in general lack the sterols and sphingolipids characteristic of eukaryotic rafts, but it is here suggested that polyisoprenoids may serve a similar function to sterols in membranes (Bramkamp, M. and Lopez, D. Exploring the existence of lipid rafts in bacteria. Microbiol. Mol. Biol. Rev., 79, 81-100 (2015); DOI).

I have expressed my reservations about the post-doc system in this blog on a number of occasions in the past. It is a dreadful waste of talent for bright young researchers to end up in a series of short-term posts with no prospects of tenured scientific positions. Many have to move into careers that are intellectually less rewarding outwith science, and at an age that limits their potential progression. It seems that the problem is now being recognized belatedly in some parts of the world at least, according to an editorial in Nature.

April 8^th, 2015

The lipoxygenases are a family of key enzymes in the eicosanoid cascade, each with precise positional and stereochemical activity against polyunsaturated fatty acids to yield a single chiral fatty acid hydroperoxide product. The reaction with each lipoxygenase involves seemingly identical mechanisms with molecular oxygen and particular pentadienyl moieties of the fatty acid at a very similar active site in each enzyme, so the question of how these distinct specificities arise has been an intriguing one, which a new review suggests may have been largely answered (Newcomer, M.E. and Brash, A.R. The structural basis for specificity in lipoxygenase catalysis. Protein Sci., 24, 298-309 (2015); DOI). There appear to be three factors involved, the first of which is the precise positioning of the fatty acid carbon chain in the active site through a control of the depth that the fatty acid can sink in towards the active site. The second factor is whether the head or the tail of the molecule enters the active site, while the third factor is from which direction the molecular oxygen enters the active site. The active site in each lipoxygenase is a U-shaped cavity with specific amino acids in fixed positions that hold the correct pentadiene unit of the fatty acid in the appropriate relationship to the catalytic iron to guarantee the required positional and chiral specificity

The organization of cholesterol and sphingomyelin into membrane subdomains termed 'rafts' is now established dogma in animal tissues. Much less is known of comparable systems in plants, but it appears that plant sterols and glycosylinositolphosphoceramides cooperate in a very similar manner (Grosjean, K. et al. Differential effect of plant lipids on membrane organization: specificities of phytosphingolipids and phytosterols. J. Biol. Chem., 290, 5810-5825 (2015); DOI).

April 1^st, 2015

The techniques of lipidomics and metabolomics are proving to be extremely important tools in the quest for improving human health by pointing to differences in metabolite formation between different physiological states. However, it is also important to know the limitations. For example, a new study reports that only two major differences in the serum metabolome of sleep-deprived over control rats were found and one of these was the diacylglycerol species 36:3 (Weljie, A.M. et al. Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt. PNAS, 112, 2569-2574 (2015); DOI). The authors don't identify the species further, but my guess would be that it is 18:1-18:2. What is its origin? Based simply on fatty acid composition, it might be the triacylglycerol fraction. While this is not usually considered as a source of distinctive metabolites, there is a first time for everything. Diacylglycerols derived from phosphatidylinositol and related lipids are important signalling molecules, but then these contain a high proportion of arachidonic acid. If the 36:3 species is derived from a phospholipid, phosphatidylcholine would seem to be the most likely precursor, but why? All good studies provide interesting questions for future work, and I suspect that the authors of this one have an interesting few years ahead.

The June issue of Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (Volume 1851, Pages 697-918) is devoted to the topic of "Phosphoinositides" (edited by A. De Matteis and P. De Camilli) and contains 20 substantial review articles. Some are too specialized for me but they clearly illustrate how complex are their interactions and how important these lipids are to innumerable aspects of metabolism in all classes of eukaryotes.

March 25^th, 2015

Scottish thistle It is not that long ago that phospholipases were considered to have relatively minor roles in lipid metabolism, being primarily concerned with phospholipid turnover and catabolism. It is now recognized that they have central functions in innumerable metabolic processes, sometimes as rate-limiting enzymes and at others stimulating signalling cascades. One key player in this field is autotaxin, a lysophospholipase D that is responsible for the generation of the important signalling lipid lysophosphatidic acid from lysophosphatidylcholine in plasma and many other tissues. A new review discusses how this enzyme works and how it is involved in chronic inflammatory diseases including cancer (Barbayianni, E. et al. Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer. Prog. Lipid Res., 58, 76-96 (2015); DOI).

A family of phospholipase A₂ enzymes occur in animal cells, although one of these - the cytosolic Ca²⁺-dependent phospholipase A₂ (the isoform cPLA₂α) - is especially important as probably the rate-limiting enzyme for eicosanoid production via release of arachidonic acid from phosphatidylinositol. A new review discusses some of the key forms of the enzyme, specifically in relation to allergies (Murakami, M. and Taketomi, Y. Secreted phospholipase A₂ and mast cells. Allergology Int., 64, 4-10 (2015); DOI). The publication is open access (there are two further reviews of interest on leukotrienes and prostanoids in this issue of the journal).

I was reminded of a paper that appeared late last year, which demonstrated that the latter enzyme was also responsible for the specific release of 15‑hydroxyeicosatetraenoic (15-HETE) acid from a storage form in phospholipids of macrophages when required for the synthesis of the pro-resolving lipid mediators, the lipoxins (Norris, P.C. et al. Phospholipase A₂ regulates eicosanoid class switching during inflammasome activation. PNAS, 111, 12746-12751 (2014); DOI).

March 18^th, 2015

In my weekly scrutiny of the lipid literature, I have come across any number of publications that relate the metabolism of lipids to cancer, both pro and con. Usually, each paper relates to a single lipid class and one specific type of cancer. A new review makes a valiant attempt to draw all these separate strings together (Huang, C.F. and Freter, C. Lipid metabolism, apoptosis and cancer therapy. Int. J. Mol. Sci., 16, 924-949 (2015); DOI). Happily, it is open access.

I have often complained about the use or rather abuse of acronyms in the titles of papers. From this week's literature search, I found 'CAD', which I correctly guessed was 'Charged Aerosol Detector', though it is more often used for a type of design software. However, who would have guessed that 'STELDI-MS' stood for 'sorptive tape-like extraction in combination with laser desorption ionization mass spectrometry'.

The March issue of Current Opinion In Clinical Nutrition And Metabolic Care is devoted to the topic of "Lipid Metabolism And Therapy" (edited by Philip C. Calder and Richard J. Deckelbaum).

March 11^th, 2015

Two analytical publications caught my eye this week. The first describes the analysis of a wide range of biologically active lipid metabolites in human plasma (Gachet, M.S. et al. A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma. J. Chromatogr. B, 976-977, 6-18 (2015); DOI). Amongst those lipids found and quantified was the endocannabinoid noladin ether, the ether analogue of 2-arachidonoylglycerol, which to my knowledge has only been reported previously from pig brain. Its concentration was close to the limits of detection so it will be interesting to see if this can be confirmed. The authors were not able to detect virodhamine, an ester or 'inverse' analogue of anandamide.

The second paper reports sensitive analyses of eicosanoids and docosanoids in urine (Sasaki, A. et al. Determination of omega-6 and omega-3 PUFA metabolites in human urine samples using UPLC/MS/MS. Anal. Bioanal. Chem., 407, 1625-1639 (2015); DOI). Amongst the analytes reported were several resolvins, i.e., docosanoids derived from omega-3 polyunsaturated fatty acids. Again, this appears to be the first time this has been accomplished.

The February issue of the Journal of Biochemistry contains three review articles under the theme of 'Recent Progress in Lipid Mediators'. The topics selected are really aimed at the specialist, but they have the virtue of being open access (as is often the case with review articles in this journal).

March 4^th, 2015

If ever there was a journal I would not have expected to cite here it is Military Medicine, produced by the Association of Military Surgeons of the U.S. However, the latest issue is devoted to a single topic - "Nutritional Armor - Omega-3 for the Warfighter". It is open access and is available as a download as a single very large pdf file (204 pages) - publications.amsus.org/pb/assets/raw/Supplements/179_11_Supplement.pdf. There is a readable 60-page review of omega-3 fatty acids as biomarkers of inflammation, followed by a number of papers by scientists who I recognise as experts in the field, including Bill Lands and Sheila Innis. Pacifists need not be put off. While many of the articles relate to the effects of EPA and DHA on trauma and performance under stress as might be expected, the findings are equally relevant to civilians. I can see the tabloid headline already - "Lipids go to War".

I have read through the special issue of BBA on eicosanoids mentioned in my blog of 3 weeks ago, and have updated a number of the web pages on this site in accordance with the new information. I was looking especially for anything new on the biochemistry of octadecanoids, i.e., the oxygenated derivatives of linoleate produced by the action of lipoxygenase and other enzymes, but there was little on the subject that I could find. These are by far the most abundant hydroxy derivatives in plasma, and they are known to be biologically active. I had hoped to find enough to create a separate web page, but I need more information. It is difficult to narrow the literature search sufficiently in any of the abstracting services to be useful. However, I did come across an interesting paper on the generation of hydroxy-oleate derivatives from linoleate by the action of microorganisms in the gut that I had missed earlier (Kishino, S. et al. Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition. Proc. Natl. Acad. Sci. U.S.A., 110, 17808-17813 (2013); DOI). A hydratase rather than an oxygenase is the key enzyme in this instance. This lead me to newer papers in press from the same lab that show protective effects of 10-hydroxy-cis-12-octadecenoic acid produced in this way on the intestinal cell walls.

There is an interesting story in Science Daily News that may explain how vitamin D and omega-3 fatty acids ameliorate the symptoms associated with a broad array of brain disorders via an action upon serotonin.

February 25^th, 2015

Scottish thistle I suppose that most of us will be familiar with the sight of plant sterols and stanols as components of nutraceuticals on supermarket shelves, not to mention the advertisements on television. There seems to be little doubt that they are beneficial in lowering plasma cholesterol levels, and I understand that the FDA in the USA accept the claims, although I don't recall seeing any major clinical study that demonstrates actual benefits against heart disease. Admittedly, I don't try too hard to keep up with the nutrition literature. A new review has planted a few seeds of doubt in my mind (Vanmierlo, T. et al. Plant sterols: Friend or foe in CNS disorders? Progr. Lipid Res., 58, 26-39 (2015); DOI). In contrast to cholesterol, plant sterols can cross the blood-brain barrier and have the potential to interfere with cholesterol metabolism in the brain - for good or ill. It seems that much more research is needed on the topic.

I have doing the weekly literature surveys on analytical methodology of lipids, which are published here monthly, for more years than I care to remember and I continue to be impressed by the numerous new papers with mass spectrometry applications. In contrast, there appears to be little exciting happening on the more chromatographic aspects of lipid analysis. Are we reaching the limits of the existing technology? I hope not - perhaps I am just a bit jaded.

February 18^th, 2015

In general, I try to follow guide lines for naming compounds when they are recommended by international agencies. For example, the term 'triacylglycerol' was recommended 50 years ago, so we should be used to it by now. Yet, I still see 'triglyceride' or worse 'triacylglyceride' used in the literature. Other considerations aside, I find 'triacylglycerol' is by far the more useful term, especially when naming molecular species. The trans-Atlantic divide as to the use of 'aluminium' (recommended internationally) versus 'aluminum' seems likely to continue. One recommendation that I have not got used to is 'icosanoid' versus 'eicosanoid'. The latter is not recommended but is used so universally that I find it difficult to buck the trend. In a quick check on Google Scholar for 2014, I found 4,000 uses of 'eicosanoid' versus only 16 for 'icosanoid'.

A recent paper on lipids from a bacterial species reports that a high proportion of the ornithine in the ornithine lipoamino acid is of the D- rather than the L-configuration. D-Amino acids are common in bacterial lipopeptides, where it is supposed that they limit the activity of proteases. I suspect that very few analysists take the trouble to determine the chirality of the amino acids in bacterial lipids, so they may be much more common than has been realized hitherto (Diercks, H. et al. Accumulation of novel glycolipids and ornithine lipids in Mesorhizobium loti under phosphate deprivation. J. Bact., 197, 497-509 (2015); DOI).

For a number of years, the American Chemical Society has allowed open access to the first issue of each journal every year. Regretfully, this dispensation appears to have been quietly dropped. Chemical journals seem to be much less open than those that are biochemically orientated.

February 11^th, 2015

A special issue of Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (Volume 1851, Issue 4, Pages 307-518) now online is devoted to the topic of "Oxygenated metabolism of PUFA: analysis and biological relevance" (edited by Michel Lagarde and Anna Nicolaou), and it is indeed special. The editors are to be congratulated for bringing together a stellar cast of authors to comprehensively review this important area. My problem now is finding time to read through them all and then to bring my web pages up to date.

I like journals with nice simple titles like 'Lipids' or 'Nature' or the simplest of all 'Gut'. 'Prostaglandins, Leukotrienes and Essential Fatty Acids' and its stable companion 'Prostaglandins and Other Lipid Mediators' are a bit of a mouthful to say the least, although we can use the abbreviation 'PLEFA' for the former now. The latest issue of PLEFA (Volume 93, Pages 1-50 (February)) is devoted to the topic of 'Cellular Lipid Binding Proteins' (edited by Jan F.C. Glatz and Betina Corsico).

'Traffic' is a simple title for a journal also, and it is not devoted to motorized transport but to biochemical pathways and inter-organelle movement. The January issue of the current year contains three articles on lipid biochemistry, which are all open access. I can especially recommend that by Professor Jean Vance which succinctly covers the large topic of phospholipid biosynthesis (Vance, J.E. Phospholipid synthesis and transport in mammalian cells. Traffic, 16, 1-18 (2015); DOI). The February issue of the journal contains two further relevant reviews (subscribers only alas).

In my last blog, I highlighted the importance of cholesterol to human metabolism. Indeed, the scientific community has recogized this by the award of 13 Nobel prizes so far for pioneering work on this lipid. Belatedly, I have just come across a review from 2013, that provides a good general review of the topic (Cortes, V.A. et al. Advances in the physiological and pathological implications of cholesterol. Biol. Rev., 88, 825-843 (2013); DOI).

February 4^th, 2015

I have always enjoyed the taste of butter and cream and have never had any qualms about their trans-content when I consumed these as part of a balanced diet. Still I was pleased to see the results of a meta analysis, which shows there is indeed no cause for concern at the normal natural levels (Gayet-Boyer, C. et al. Is there a linear relationship between the dose of ruminant trans-fatty acids and cardiovascular risk markers in healthy subjects: results from a systematic review and meta-regression of randomised clinical trials. Brit. J. Nutr., 112, 1914-1922 (2014); DOI).

A special issue of the Journal of Inherited Metabolic Disease (Volume 38, Issue 1 of 2015) is devoted to the topic of "Complex lipids", with the emphasis of course on in-built errors of metabolism (edited by Jean-Marie Saudubray, Matthias R. Baumgartner and Ronald Wanders).

Cholesterol is one of the bogymen of nutrition, and you are unlikely to find a good word about it in any newspaper or popular magazine. Lipid scientists know better. Cholesterol is essential in membranes and as a precursor of hormones, vitamin D and bile acids amongst a myriad of functions. A recent review provides a reminder of another function, i.e., as a major regulator of ion channel function in cells involving specific sterol-protein interactions (Levitan, I. et al. Cholesterol binding to ion channels. Front. Physiol., 5, 65 (2014); DOI). The specifics may only be of interest to specialists, but the paper is open access so is easy to view.

January 28^th, 2015

Scottish thistle Lysophosphatidic acid is now recognized to be a key signalling molecule in animal metabolism. One particular finding has stood out - reports that its concentration is markedly elevated in the plasma of ovarian cancer patients compared to healthy controls, suggesting that it may represent a useful marker for the early detection of the disease. It is believed to stimulate DNA synthesis and the proliferation of ovarian and other cancer cells. A new meta-analysis has now confirmed that "The LPA assay showed high accuracy and sensitivity for the diagnosis of ovarian cancer". Although the number of studies in the meta analysis was smaller than ideal, the conclusions are quite clear (Lu, Z.L. et al. Diagnostic value of total plasma lysophosphatidic acid in ovarian cancer: a meta-analysis. Int. J. Gynecological Cancer, 25, 18-23 (2015); DOI).

Over last 5 years, there have appeared a number of publications describing the occurrence of novel arsenolipids in fish oils and other marine sources. These lipids include hydrocarbons, alcohols, fatty acids, and a complex glycophospholipid. The fatty acids had only been detected in unesterified from, but a new publication demonstrates that they are also present esterified to triacylglycerols (Taleshi, M.S. et al. Arsenolipids in oil from blue whiting Micromesistius poutassou - evidence for arsenic-containing esters. Sci. Rep., 4, 7492 (2014); DOI). An initial conclusion that the presence of most of these lipids in fish oils does not appear to raise toxicity problems when they are consumed by mammals may now have to be challenged, as arsenic-containing hydrocarbons were recently reported to be highly toxic in tests with cultured cells from human bladder and liver and in studies with Drosophila melanogaster (two papers in the journal Metallomics).

In my blog last week, I highlighted the importance of work on the lipids of Mycobacterium tuberculosis. A year after formal publication, a review on the mycolic acids has just been made open access and can be recommended to those with an interest in these lipids (Marrakchi, H. et al. Mycolic acids: structures, biosynthesis, and beyond. Chem. Biol., 21, 67-85 (2014); DOI)

January 21^st, 2015

In my blog of December 26th, I pointed out how studies of cell wall lipids, specifically lipid A, were aiding the search for new anti-bacterial drugs. A further approach to this problem deals with the search for novel microbial lipopeptides, many of which are already known to have potent antibacterial, antiviral or even anticancer properties. As many of these function by disrupting the membranes physically, it seems possible that microorganisms are much less likely to acquire resistance to them. A new review describes those found in the genus Bacillus and related genera (Cochrane, S.A. and Vederas, J.C. Lipopeptides from Bacillus and Paenibacillus spp.: a gold mine of antibiotic candidates. Medicinal Res. Rev., in press (2015); DOI). While many of those already known are more toxic to potential patients than we would like, they can be used topically, and some have been licensed as a treatment of last resort against drug-resistant strains of pathogenic bacteria. Some structural modifications have also been made by chemical and biochemical means to reduce toxicity.

Incidentally, while reading through this review to update my web page on the subject, I came across a reference to a fatty acid that was described in 1996 (though I was not aware of it) and appears to be completely unique, i.e., 15-guanidino-3-hydroxypentadecanoic acid found in fusaricidins, which are cyclic lipopeptides from Paenibacillus spp. The formula is illustrated here as such an unusual fatty acid should be better known (and it is discussed in our web page on bacterial lipopeptides).

15-guanidino-3-hydroxypentadecanoic acid from fusaricidins

Continuing the microbiological theme, I can recommend a new review of the trehalose lipids of Mycobacterium tuberculosis. Here again, the hope is that more and better knowledge of the lipids and their biosynthetic pathways will lead to better drugs against a disease that still kills over a million people world-wide each year (Nobre, A. et al. The molecular biology of mycobacterial trehalose in the quest for advanced tuberculosis therapies. Microbiology, 160, 1547-1570 (2014); DOI). This publication is open access.

January 14^th, 2015

The Archaea are a separate kingdom of life that is distinguished from Bacteria by innumerable factors, not least their lipid components. In particular, the latter contain isoprenoid alkyl moieties attached by ether linkages to the sn-2 and sn-3 positions of glycerol, not the sn-1 and sn-2 positions as in Bacteria and Eukaryotes. The alkyl moieties are themselves distinctive in that they contain 20 or 40 carbons, with the latter attached to a second glycerol moiety. One explanation for the biosynthesis of these lipids is that two twenty carbon alkyl moieties on separate molecules join tail to tail. If this indeed turns out to be the case, it will be unprecedented in biochemistry. The other striking feature of the lipids with 40-carbon alkyl moieties is that they span the membrane in effect producing a monolayer with the properties of a bilayer. There is a web page on these fascinating lipids on this web site here (Archaeal ether lipids), but for anyone requiring a more detailed knowledge I can recommend a new review (Jain, S. et al. Biosynthesis of archaeal membrane ether lipids. Front. Microbiol., 5, 641 (2014); DOI), which happily is open access.

The same group has also published an important paper that for the first time defines one of the key enzymes in the biosynthesis of Archaeal lipids (Jain, S. et al. Identification of CDP-archaeol synthase, a missing link of ether lipid biosynthesis in Archaea. Chem. Biol., 21, 1392-1401 (2014); DOI).

January 7^th, 2015

Stereospecific analysis of triacyl-sn-glycerols, i.e., the determination of the fatty acid compositions of each of the three positions, is a daunting task involving a number of steps - degradative, synthetic, enzymatic and chromatographic. Unfortunately, it appears to require a combination of skills (and patience to learn them) that are slowly being lost, as I see very few new reports in the literature these days. Mass spectrometric methods are being used for regiospecific analysis, i.e., for distinguishing the composition of position sn-2 from the average of the two primary positions of triacylglycerols, but there seems to be little prospect of applications of this technique to stereospecific analysis. At a personal level, I find this a matter of regret in that the stereospecific methodology was important to my early career, but more generally it will be a loss to science if the few remaining centres of excellence in this area move onto other things.

The only prospect that cheers me up is the appearance of some recent papers showing that it is possible to separate enantiomeric triacylglycerols by chiral chromatography. This I would not have expected, as the optical activity of most natural triacylglycerols is too low to be measured, and I would not have expected interactions with chiral phases to be sufficient for separations. Nonetheless, some excellent resolution has been achieved as the two papers listed can attest (Kalpio, M. et al. Enantioselective chromatography in analysis of triacylglycerols common in edible fats and oils. Food Chem., 172, 718-724 (2015), DOI; Rezanka, T. and Sigler, K. Separation of enantiomeric triacylglycerols by chiral-phase HPLC. Lipids, 49, 1251-1260 (2014), DOI). They do not yet indicate a new approach to stereospecific analysis but who knows what is round the corner.

Blogs for the previous year (2014) can be located here..

© Bill Christie
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