The LipidWeb blank

Lipid Matters - A Personal Blog

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

July 15th, 2020

Scottish thistleMuch of my former research interests were in analytical methodology, and I always felt flattered when I saw a method that I had developed being applied by others. On the other hand, I recall the eminent plant lipid biochemist Paul Stumpf documenting an instance of an author deliberately omitting a step in a published method so he could keep ahead of the opposition (Stumpf, P.K. A retrospective view of plant lipid research. Prog. Lipid Res., 33, 1-8 (1994);  DOI). Thankfully, I do not believe that this is a frequent occurrence.

Many times over the years, I have had arguments with journal editors about how much practical information should go into the 'Experimental' section of papers. When others try to repeat a published method, it is often minor details that are important. The primary concern of editors is often to save space, and this may not coincide with the interests of readers - hence the perennial cry -"why does your method not work when I try it?" On occasion, errors arise because of imprecision on the part of authors. For example, a procedure carried out at "room temperature" in Dundee may be several degrees C different from that in Arizona. In summer, the latter may even be cooler because they have air-conditioning - a facility not often required in Scotland! Suppliers can make changes to their products as "improvements". For example, my former colleagues had great difficulties with the work-horse GC columns they used, because the manufacturer had changes the chemistry of the stationary phase slightly - sufficient to render one key separation no longer possible, even if other aspects were arguably better. The more honest of us will confess that we may occasionally have difficulties in repeating some of our own published methods after a key worker has left, so it is hardly surprising that others have this difficulty also. Every lab needs someone with "green fingers" for the difficult tasks.

July 8th, 2020

While our eyes are focussed on Covid, it does not do to forget that there are many other nasty organisms out there, not least M. tuberculosis, which is reported to kill over 1,000,000 people every year. This is one where we really do have to blame the lipids. A key factor in the persistence of M. tuberculosis infections is its distinctive cell wall, a high proportion of which consists of complex and often unique lipids, which confer extreme hydrophobicity to the outer surface, resist degradation by host enzymes, including those of the immune system, and by antibiotics, and so are associated with its pathogenicity. It has a distinctive dual membrane structure that is neither fully Gram-negative nor Gram-positive. The outermost layer consists of free waxy lipids, while the inner membrane structure is enriched in phosphatidylinositol mannosides. In between, the complex mycolic acids link to both membranes and provide structural support to the cell wall. Another unusual feature is that biosynthesis of the aliphatic constituents requires an interplay between fatty acid synthases I and II and polyketide synthases. A new review provides a clear and accessible account (Batt, S.M. et al. The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system. Biochem. J., 477, 1983-2006 (2020);  DOI).

It was not too difficult for John Harwood to pull me out of retirement from more formal publication to act as a coauthor on his overview of lipoxins as part of a series of articles for Essays in Biochemistry, published by the Biochemical Society. It is accessible ahead of print here... Many more relevant reviews in this series are now freely available from the journal ahead of publication.

July 1st, 2020

I recall in the days when I worked in a dairy research institute that I wrote that anyone who wanted to stretch their methodology to the limit should try it out on milk fat. I am therefore greatly impressed by a new publication in which 3454 molecular species of triacylglycerols were identified with 65 fatty acid constituents (Liu, Z.Q. et al. Comprehensive characterization of bovine milk lipids: triglycerides. ACS Omega, 5, 12573-12582 (2020);  DOI - open access). Regio- and stereo-isomers were not resolved, unsurprisingly, but this is still a quite exceptional achievement.

There is as ever a "but". What can outside observers do with this information? Over the years, I have produced a number of review papers comparing triacylglycerol compositions from different species, tissues and so forth, but I have never been able to tabulate molecular species data in making comparisons - this is simply impractical. Rather, I have tabulated and compared positional distributions, most recently on a web page here... No recently acquired data are listed as few are available. I extolled the virtues of stereospecific analysis methods for biosynthesis and metabolic studies in a recent blog, and this seemed to generate some interest. Therefore, I have substantially adapted, rewritten and updated an older article on the subject, and this is now online on this website here... There has been a tendency in the literature to assume that position sn-2 of triacylglycerols is most important, simply because it has been so easy to determine by means of hydrolysis with pancreatic lipase and now by mass spectrometry. However, position sn-3 can have an equally distinctive composition, and position sn-1 is not far behind.

I am sure that I am not alone in being confused by nutritional recommendations regarding the intake of fatty acids. A new review takes issue with American Heart Association (AHA) for strongly recommending a reduction in dietary saturated fats, and it suggests that "the strength of the evidence for the recommendation to limit SFAs for heart disease prevention may be overstated and in need of reevaluation" (Heilson, J.L. Dietary saturated fat and heart disease: a narrative review. Nutr. Rev., 78, 474-485 (2020);  DOI). I have only seen the abstract of the paper, but I enjoy butter and cream and at my age I am passed caring.

June 24th, 2020

Scottish thistleArsenic-containing organic compounds soluble in organic solvents and therefore termed 'arsenolipids' have long been known to exist in nature, but those I would describe as true lipids, defined as containing aliphatic chains and arsenic, are more recent discoveries. They are potentially a cause for concern as they are found as minor components of fish oils. So far, it appears that only hydrocarbons containing arsenic present a toxicity problem, and these are detected at such low levels that they are not seen as a threat. The other source of arsenolipids in the human diet are seaweeds, which are in fact multicellular algae. These contain a distinctive glycophospholipid in which the arsenic-containing unit is a monosaccharide unit. A new study describes the determination of molecular species compositions and positional distributions of this lipid in seaweeds harvested for human consumption by using a combination of mass spectrometry and regiospecific enzymatic hydrolysis (Coniglio, D. et al. Arsenosugar phospholipids (As-PL) in edible marine algae: an interplay between liquid chromatography with electrospray ionization multistage mass spectrometry and phospholipases A1 and A2 for regiochemical assignment. J. Am. Soc. Mass Spectrom., 31, 1260-1270 (2020);  DOI).

Arsenic-containing glycophospholipid

Although it is not the first time comparable methodology has been used for this particular lipid class, I wanted to draw attention to this paper in view of my comments in my last blog and in earlier posts about what I perceive as the relative neglect of methods involving regiospecific hydrolysis of lipids. In the past I have challenged readers to compare positional distributions determined solely by mass spectrometry, with those that are more precise, for minor components especially, by using regio- or stereospecific enzymes. So far no takers!

I don't suppose that all viruses function in the same way, but a new review of the sneaky ways that the hepatitis C virus takes over lipid metabolism in its host is worth a read (Bley, H. et al. Whole lotta lipids-from HCV RNA replication to the mature viral particle. Int. J. Mol. Sci., 21, 2888 (2020);  DOI). This review covers just the last 5 years or so of research, but may demonstrate how much needs to be done before we have as full an understanding of Covid.

June 17th, 2020

As should be well known, natural triacylglycerols are chiral molecules and all three positions can be occupied by different fatty acids. Perhaps the best known example is cow's milk, in which the short-chain fatty acids (4:0 and 6:0) are exclusively in position sn-3. However, there are many other natural triacylglycerols with distinctive distributions and you can find a summary here... Chiral phase chromatography is only able to resolve a few enantiomeric triacyl-sn-glycerol species, and it is a significant achievement to show that this can be accomplished for some with uncommon fatty acid components, for example - (Palyzova, A. and Rezanka, T. Enantiomeric separation of triacylglycerols containing fatty acids with a ring (cyclofatty acids). J. Chromatogr. A, 1622, 461103 (2020);  DOI).

For a good part of my research career, I was interested in methodology to determine the compositions of each of the three positions, and this has always been something of a technical challenge. I last reviewed this online some years ago here.. Several methods have been developed with most having a preliminary step in which triacyl-sn-glycerols are hydrolysed to a mixture of sn-1,2- and sn-2,3-diacylglycerols, which can be derivatized in various ways for chiral separation or for reaction with stereospecific enzymes. All are time-consuming and require some technical skill, and it is disappointing to report that it is some years since I last saw a paper in which the methodology was applied. Yet it is surely as important now to be able to distinguish the compositions of the three positions as it ever was if we are to understand fully the enzymology of triacylglycerol biosynthesis and hydrolysis. Mass spectrometry cannot distinguish between positions sn-1 and sn-3 in triacylglycerols, i.e. it is regiospecific not stereospecific, and my concern is that the new generation of lipid analysts are unwilling to tackle problems that cannot be solved by this technique.

If I had to pick one natural sample for full stereospecific analysis, I would select a unique triacylglycerol that is a single molecular species consisting of only three fatty acids 16:1-12:0-18:1 in an organelle termed the midbody in dividing cells in humans (Atilla-Gokcumen, G.E. et al. Dividing cells regulate their lipid composition and localization. Cell, 156, 428-439 (2014);  DOI) and subsequently in rodents. I am sure that this must have a distinctive structure and function.

June 10th, 2020

On the face of it the nematode Caenorhabditis elegans seems a strange model for the study of lipids in animals, but the ease of dietary supplementation and genetic manipulation permits examination of the function of polyunsaturated fatty acids and oxylipins in many biological processes over short time-scales that include aging, reproduction, and neurobiology, as discussed in a new review (Mokoena, N.Z. et al. Synthesis and function of fatty acids and oxylipins, with a focus on Caenorhabditis elegans. Prostaglandins Other Lipid Mediators, 148, 106426 (2020);  DOI). However, it is the differences from the pathways in higher animals that immediately catch the eye, as these organisms have all the enzymes to produce the full suite of polyunsaturated fatty acids considered essential in the latter. They have a wide range of CYP450 enzymes to produce C20 oxylipins also, but they lack the cyclooxygenase enzymes to synthesise prostaglandins. On the other hand, they are able to produce a molecule that appears identical to prostaglandin F (subject to a check on stereochemistry) by some as yet unknown mechanism. Although not discussed in this review, nematodes have an unusual requirement for branched-chain fatty acids, while in the reproductive stage, they produce unusual glycolipids - ascarosides.

The English language is reputed to contain several times more words than any other, but there is always room for one more as in the title of this review (Hofer, P. et al. The lipolysome - a highly complex and dynamic protein network orchestrating cytoplasmic triacylglycerol degradation. Metabolites, 10, 147 (2020);  DOI - open access). "Lipolysome" is defined as the complex lipolytic machinery in cytoplasmic droplets.

June 3rd, 2020

Methods of increasing technical sophistication and therefore cost are being applied more and more to the analysis of the lipidome. However, from time to time, I have the impression that relatively straight-forward methods from the pre-lipidomics era, i.e. 20 years ago, are being forgotten. I have described before how my mentor Frank Gunstone characterized the first natural epoxy fatty acid, vernolic acid, in the 1950s without any kind of chromatography or spectroscopic equipment, but merely a balance, a burette and his knowledge of chemistry (this blog, January, 2019).

Not that I recommend going back to those days, but if we consider simply determination of double bond positions, branch points, etc, in fatty acids and other aliphatic compounds, there are a number of simple chemical reactions that can give detailed structural information with the aid of gas chromatography and the simplest of bench-top mass spectrometers. For example, if there is only one double bond, a one-pot reaction with dimethyl disulfide gives an adduct that enables both the position and the geometry of the double bond to be determined. If the carboxyl group is derivatized to produce pyrrolidides, 4,4‑dimethyloxazolines or 3‑pyridylcarbinols, highly complex natural fatty acid mixtures with many different functional groups in the alkyl chains can be characterized definitively by GC-MS. My colleagues and I were able to identify as many as 120 different fatty acids in single samples of marine origin by this means, for example. Indeed, a surprising amount of structural information can be obtained on branched-chain and polyunsaturated fatty acids simply from methyl ester derivatives (see the Mass Spectrometry pages on this web site).

Please do not think that I am trying to denigrate what is being achieved by modern mass spectrometric methodology for fatty acid analysis in intact lipids by using ozonolysis, the Paternò-Büchi reaction and others, as I sometimes regret that I reached the age of retirement before such techniques were available or affordable. I merely want to point out to a younger generation that alternative methodologies are tried, tested and efficient, and may offer advantages in many situations.

May 27th, 2020

Scottish thistleLeaf and other tissues in plants contain a range of sterol glycosides and sterol acyl-glycosides in which the hydroxyl group at C3 on the sterol is linked to the sugar by a β-glycosidic bond. Such lipids have only rarely been found in animal tissues, although cholesterol glucoside (1-O-cholesteryl-β-D-glucopyranoside) and less often cholesterol acyl-glucoside have been detected, and were found first in the skin of snakes and birds. Now both cholesterol glucoside and galactoside have been shown to be present throughout development in mouse brain from the start of myelination in embryos through to adults, with biosynthesis involving a transfer of glucose/galactose from cerebrosides to cholesterol catalysed by a lysosomal β-glucocerebrosidase (Akiyama, H. et al. Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly-identified brain sterol metabolite, galactosylated cholesterol. J. Biol. Chem., 295, 5257-5277 (2020);  DOI). It will be interesting to know what their function is there.

In plants, sterol glycosides are synthesised by a very different mechanism, i.e. from free sterols with a glucose unit catalysed by a sterol glycosyltransferase, or by reaction of the sterol with uridine diphosphoglucose (UDP-glucose) and UDP-glucose:sterol glucosyltransferase on the cytosolic side of the plasma membrane. In this instance, they are believed to have a number of biological functions, for example in the adaptation of plant membranes to low temperatures and other stresses, in the response to fungal pathogens and in signal transmission. A new review discusses findings that through acting as immunoadjuvants, sterol glycosides are efficacious in protecting animals against lethal Cryptococcal infections (Normile, T.G. et al. Steryl glycosides in fungal pathogenesis: an understudied immunomodulatory adjuvant. J. Fungi, 6, 25 (2020);  DOI - open access). Does this give us a clue as to the function of the endogenously synthesised lipid in animals?

Last question - is the correct nomenclature "sterol glycosides" or "steryl glycosides"?

May 20th, 2020

Two publications dealing with analytical methodology have caught my eye this week, and happily both are open access. The first deals with a particularly taxing problem, i.e. the analysis of those acyl moieties attached to acyl-carrier proteins, which are of course not only intermediates but the products of fatty acid synthesis in plants (Nam, J.-W. et al. A general method for quantification and discovery of acyl groups attached to acyl carrier proteins in fatty acid metabolism using LC-MS/MS. Plant Cell, 32, 820-832 (2020);  DOI). The authors were able to identified acyl-ACP elongation intermediates (3-hydroxy-acyl-ACPs and 2,3-trans-enoyl-ACPs and medium-chain-ACPs, together with polyunsaturated long-chain acyl-ACPs (16:3) that might not have been anticipated. The methodology will of course be invaluable for the development of genetically modified seed oils, as the authors intend, but interesting questions regarding fatty acid metabolism in chloroplasts are also posed. Although the method is described for plants, it should be applicable to mammalian systems as it involves a preliminary step of hydrolysis at a highly conserved amino acid sequence in ACPs retaining the phosphopantetheinyl linker to which acyl groups attach.

The second publication is a review less of analysis per se but more of the results of analyses of carnitines and acyl-carnitines (Bene, J. et al. Mass spectrometric analysis of L-carnitine and its esters: potential biomarkers of disturbances in carnitine homeostasis. Curr. Mol. Med., 20, 336-354 (2020);  DOI). As is well known, carnitine plays a vital role in the mitochondrial oxidation of long-chain fatty acids by enabling them to cross the inner mitochondrial membrane, although it has wider functions in cells by controlling the acyl-CoA/CoA ratio thereby influencing innumerable enzyme systems. Screening of the carnitine ester profile of newborn infants is well established and can lead to the detection of more than 30 metabolic disorders, but this methodology is now proving useful in investigating diseases of adult patients, including diabetes and cardiovascular diseases.

The Journal of Lipid Research and the Journal of Biological Chemistry already have enlightened access policies, but I was delighted to learn that they will become fully open access soon. Now if only the major chemical societies would follow suit - over to you ACS and RSC!

May 13th, 2020

When I was starting to write my web pages on different lipid classes in the Lipid Essentials section of this website, I had most problems with that on cytidine diphosphate diacylglycerol (CDP-DAG), in spite of the fact that it is a key intermediate that occupies a branch point in the biosynthesis of certain complex glycerolipids, especially phosphatidylinositol and cardiolipin. For example, it was extremely difficult to find any compositional data, and I had to rely on a publication from 1976 (as an aside, I should not apologize for this, as the work is probably as sound as anything published more recently). Modern mass spectrometric methods do not appear to be sufficiently sensitive to detect this lipid in natural tissues - if anyone out there is interested, it might be a useful project for someone to find a means of concentrating this lipid so it can be analysed more easily in order to have compositional information for different tissues. There have been some valuable new findings in recent years, especially the characterization of three distinct CDP-DAG synthases with differing subcellular distributions and differing products. Now, two substantial reviews on the topic have come along at the same time (Blunsom, N.J. and Cockcroft, S. CDP-diacylglycerol synthases (CDS): gateway to phosphatidylinositol and cardiolipin synthesis. Front. Cell Dev. Biol., 8, 63 (2020);  DOI: and - Jennings, W. and Epand, R.M. CDP-diacylglycerol, a critical intermediate in lipid metabolism. Chem. Phys. Lipids, 230, 104914 (2020);  DOI).

We need now to take note that CDP-DAG synthases, as a regulators of phospholipid metabolism and the rate-limiting enzyme in phosphatidylinositol biosynthesis, have a key role in the regulation of signal transduction processes dependent upon this lipid and thence indirectly in diseases related to faulty lipid metabolism. Similarly, it influences the availability of phosphatidic acid for biosynthesis both of triacylglycerols and of complex lipids and for its signalling activities.

May 6th, 2020

In some types of glycosylphosphatidylinositols (protein anchors), the first mannose unit is decorated by the addition of a short oligosaccharide sequence starting with N-acetylgalactosamine, before galactose is added. A new publication shows that this step involves the action of a GM1 ganglioside synthase and requires the presence of lactosylceramide (Wang, Y. et al. Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation. Nature Commun., 11, 860 (2020);  DOI - open access). It is thus an interesting link between glycerolipid and sphingolipid metabolism.

Some years ago, in the question session after a presentation, I was asked if I knew of links of this kind. Only two sprang immediately to mind - the biosynthesis of sphingomyelin requiring phosphatidylcholine as precursor, while ethanolamine phosphate derived from the catabolism of sphingolipids via sphingosine 1-phosphate is recycled for the biosynthesis of phosphatidylethanolamine. I was sure there were more and of course, once I was on my way home, I thought of others. I began to make a list, and eventually, I decided that this should be shared so I added a short section to my web page Introduction to Sphingolipids. Although more items have been added from time to time, I am sure that this list is far from complete, so I would be grateful for suggestions of further examples.

We must all be rethinking our relationship with the world and our environment during the Covid crisis. A new review on the application of lipidomics adds food for thought (Koelmel, J.P. et al. Environmental lipidomics: understanding the response of organisms and ecosystems to a changing world. Metabolomics, 16, 56 (2020);  DOI). Incidentally, there are three further reviews of various aspects of lipidomics in the current reference list(May) in the Literature Survey section of this web site.

April 29th, 2020

Scottish thistleA paper in press suggests a novel potential application of a common simple lipid as an antibiotic in nasal, tracheal, and bronchial epithelial cells (Verhaegh, R. et al. Sphingosine kills bacteria by binding to cardiolipin. J. Biol. Chem., in press (2020);  DOI). The authors show that unesterified sphingosine in protonated form rapidly causes death in a number of important bacterial pathogens by binding to the negatively charged lipid cardiolipin in bacterial plasma membranes. The suggestion is that the mechanism involves rapid permeabilization of the plasma membrane by promoting clustering of cardiolipin molecules in the membrane to generate gel- or even crystal-like structures. Sphingosine administered for antibiotic purposes is unlikely to reach cardiolipin in mitochondria in animal tissues, but I wonder whether some of the biological properties assigned separately to sphingosine and cardiolipin present endogenously in cells might be due to the two lipids acting in concert.

On a number of occasions over the last 15 years in this blog, I have drawn attention to the poor career prospects of most post-doctoral researchers in British Universities (not that the UK is unique in this respect). They may not be regarded overtly as a source of cheap and disposable labour, but this is the often the result. Nothing seems to change. The problem is likely to be exacerbated by the current financial problems of universities, and may even have become a feminist issue, as an article in the Guardian newspaper suggests.

April 22nd, 2020

I can remember when lysophospholipids were regarded merely as nasty lipids that would disrupt cell membranes if they were not rapidly catabolized or re-esterified. Their occurrence in lipid extracts was viewed as an artefact of a faulty extraction procedure (still true if too abundant). Now they are listed among the more important of lipid mediators with key functions in signalling, especially if sphingosine-1-phosphate is included in their number. I highlighted their potential use to deliver polyunsaturated fatty acids to brain in my blog of two weeks ago. Now a new publication describes yet another important function. It is reported that the phospholipase iPLA2γ hydrolyses fatty acids from position sn-1 of phospholipids to generate polyunsaturated sn-2-acyl lysophospholipids. In murine myocardium and in isolated platelets, human platelet-type 12-lipoxygenase (12-LOX) can then directly catalyse the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine and 2-arachidonoyl-lysophosphatidylethanolamine to produce 2(S)-HETE products, which can initiate signalling pathways. As these increase in concentration with age, they "may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions" (Liu, X. et al. 12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2γ knockout. J. Biol. Chem., 295, 5307-5320 (2020);  DOI). There is a growing list of oxidized phospholipids that have biological activity in intact form (on this website see - here.. and here..)

I am grateful to a correspondent who pointed out an error in my structural formulae for the furanoid fatty acids (via the link) highlighted in my last blog; corrections or suggestions for improvements are always welcome. Another correspondent has drawn my attention to a useful online data base of plant fatty acids. He also sent a copy of a new review on a related topic, which I will enjoy reading in self-isolation (Cahoon, E.B. and Li-Beisson, Y. Plant unusual fatty acids: learning from the less common. Curr. Opinion Plant Biol., 55, 66-73 (2020);  DOI).

April 15th, 2020

For many years, I was puzzled by the appearance of minor components in GC-MS traces of fish oil methyl esters, the mass spectra of which bore no resemblance to conventional fatty acids. Eventually, a colleague suggested that they were furanoid fatty acids, and this proved to be correct. Once I knew what to look for I found them in every fish oil sample that I looked at, and especially in fish oil concentrates prepared for nutraceutical purposes (analysed by Mylnefield Lipid Analysis to which I was a consultant until recently). I am sceptical of a recent claim that they can be formed artefactually from EPA and DHA in pharmaceutical preparations. However, their precise origin is uncertain, although it is believed to be somewhere in the marine food chain, probably algae. In fish, they tend to be concentrated in reproductive tissues, although their function is unknown.

When consumed by humans, furanoid fatty acids have generally been suggested to have benign functions as antioxidants with cardioprotective effects. However, short-chain metabolites or "urofuranic acids", beta-oxidation metabolites of the longer-chain components from fish in the diet, are found in plasma, and when kidney function is impaired one isomer in particular, i.e. 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), can accumulate and is reported to be a significant uremic toxin. Its concentration increases in plasma of patients who progress from prediabetes to type 2 diabetes also, and it may be a marker for this disease; it increases oxidative stress and impairs insulin secretion. Analysis has always been a technical challenge, but a new LC-MS/MS technique with charge-reversal derivatization appears to be the answer (Xu, L. et al. Development of a sensitive and quantitative method for the identification of two major furan fatty acids in human plasma. J. Lipid Res., 61, 560-569 (2020);  DOI). Hopefully, the availability of the method will enable a better understanding of the metabolic consequences.

April 8th, 2020

I don't believe that I am unique in being confused by nutritional science in relation to recommendations for the intake of specific fatty acids, especially for eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. As far as I can understand it, the evidence that supplementation in the early years of life is a good idea seems to be fairly solid. On the other hand, this may not continue to be true as children get older. Unfortunately for myself, increased intake of these fatty acids does not seem to help with cognitive decline in the elderly, and the jury seems to be out on whether it helps with neurological diseases. On the other hand, there is a school of thought that conventional supplementation of the diet with these fatty acids does not help because they cannot cross the blood-brain barrier with sufficient rapidity to enter the brain where they are needed. There have been a few publications recently suggesting that this problem can be circumvented if they are administered as esters of lysophosphatidylcholine. A new paper describes this work and especially a relatively stable analogue, i.e. 1-acetyl,2-docosahexaenoyl-glycerophosphocholine, which has the potential to be supplied orally (Hachem, M. et al. Brain targeting with docosahexaenoic acid as a prospective therapy for neurodegenerative diseases and its passage across blood brain barrier. Biochimie, 170, 203-211 (2020);  DOI).

The most recent paper I have seen on analysis of fatty acid esters of hydroxy fatty acids (FAHFA) nearly doubles the number of reported molecular species in rat adipose tissue to over 300 (Zhu, Q.F. et al. FAHFA footprint in the visceral fat of mice across their lifespan. Biochim. Biophys. Acta, 1865, 158639 (2020);  DOI). They are known to have anti-inflammatory and anti-diabetic effects. I suppose that we must classify them as oxylipins, although we tend to think of most such lipids as being produced under strict stereospecific and regiospecific control. It is not yet known whether FAHFA have a specific receptor, but if so does it really handle such a wide range of isomeric compounds?

April 4th, 2020

News of the untimely death of Michael Wakelam from Covid-19 came as a great shock. I first met him when he was a lecturer at Glasgow University in the 1980s, and I followed his career via his publications with great interest thereafter. It was he who invited me to add my blog and later this website to that of LipidMaps. Lipid science will be much the poorer for his passing.

April 1st, 2020

Two further brief autobiographies of lipid scientists have appeared this week - good reading matter at any time, but especially when in self-isolation. The first is by Howard Goldfine (Life without air. J. Biol. Chem., 295, 4124-4133 (2020);  DOI - open access). I first became aware of his work on cyclopropane fatty acids when I worked briefly on their chemical synthesis in my post-doc years. More recently, among a substantial body of work on microbial lipids, his work on plasmalogen biosynthesis in anerobic bacteria is ground-breaking, even if we don't have all the answers yet; unlike animal systems, the required enzymes do not need molecular oxygen.

The second of these autobiographies is by Robert C. Murphy (Lipid mass spectrometry: A path traveled for 50 years. J. Mass Spectrom., e4492 (2020);  DOI), who will be well known to users of the LipidMaps website, and whose name is synonymous with mass spectrometry of lipids. His book on this topic in the Handbooks in Lipid Research series was a well-used item on my book shelf, and now probably resides with one of my former colleagues. I had forgotten his early contribution to what was then known as the "slow reacting substance of anaphylaxis", which on sabbatical at the Karolinska Institute in Sweden he identified as the lipid mediator we now know as leukotriene C4. Since then, he has produced an enviable number of publications that are truly pioneering on the chemistry and biochemistry of eicosanoids, as well as on complex lipids. His studies based on the use of mass spectrometry have enabled us to look at the biochemistry of lipids in living systems at minute concentration that were unthinkable to earlier generations of scientists. He is one of the first I would list among those who have established "lipidomics" as a science.

A useful summary paper concludes a thematic series on the biological functions of phosphatidylserine (Calianese, D.C. and Birge, R.B. Biology of phosphatidylserine (PS): basic physiology and implications in immunology, infectious disease, and cancer. Cell Comm. Signal., 18, 41 (2020);  DOI). The various parts have been appearing over recent months.

March 25th, 2020

Scottish thistleIn the cell envelope of Gram-positive bacteria, there are usually two types of polyanionic polymers linked either to membrane diglycosyldiacylglycerols, i.e. lipoteichoic acids (LTA), or to peptidoglycans, i.e. wall teichoic acids (WTA), which together form a dense protective layer against the environment. The anionic polymer units in both appeared to be superficially the same in that they consisted of repeating glycerol-phosphate units decorated in various ways. However, it is evident that degradative enzymes discriminate between the two. It has now been demonstrated that in LTA, the repeating units consist of sn-glycerol-1-phosphate while in WTA they are sn-glycerol-3-phosphate. In other words, they are stereochemically distinct (Walter, A. et al. Phosphoglycerol-type wall and lipoteichoic acids are enantiomeric polymers differentiated by the stereospecific glycerophosphodiesterase GlpQ. J. Biol. Chem., 295, 4024-4034 (2020);  DOI - open access as author's choice). This adds weight to my recent blog in which I stressed the importance of the difference between regiospecific and stereospecific nomenclatures for glycerol derivatives.

I am appreciative of the policy of the Journal of Lipid Research in providing commentaries on articles, which the editors consider of special importance. Like most scientists, I scan the titles of innumerable new publications every week, and it is very easy to miss some that I ought to read. It is impossible to be an expert on everything, and I am grateful for any help that I can get. One such commentary appeared in press this week to discuss a paper also in press describing how unesterified fatty acids cross membranes (Pownall, H.J. J. Lipid Res.,  DOI - open access). The conclusion is that this occurs largely by a simple diffusion mechanism or 'flip-flop'. The process is not unregulated as sometimes suggested, nor is it controlled via the activity of specific transporters, but simply by the "balance between intracellular triacylglycerol synthesis versus hydrolysis, which transfer long-chain fatty acids into or liberate them from fat droplets, respectively".

March 18th, 2020

Some years ago, a colleague was contacted by a poultry company because the yolks of their eggs had a peculiar consistence. Not surprisingly, it turned out that they were using a less costly unrefined cotton seed oil in their feed, as it was well established that traces of cyclopropenoid fatty acids in this oil reacted with thiol groups and in particular inhibited stearoyl-CoA desaturase with dramatic effects upon the fatty acid composition and thence upon the properties of eggs. However, I was rather surprised to find in a new review that this activity now has clinical potential for use of this fatty acid as an adjuvant in diseases such as cancer, nonalcoholic steatohepatitis and skin disorders. It may also have a protective roles in retinal diseases such as age-related macular degeneration (Pelaez, R. et al. Sterculic acid: the mechanisms of action beyond stearoyl-CoA desaturase inhibition and therapeutic opportunities in human diseases. Cells, 9, 140 (2020);  DOI - open access).

Gangliosides are another class of lipids involved in human disease states. Meat eaters and milk drinkers, including the human neonate, consume small amounts of these, but I had not realized that they had an influence upon human metabolism as dietary constituents. After all they are catabolized in intestinal tissues with release of their lipid and carbohydrate constituents. However, it appears that the sialic acid residues are re-utilized for ganglioside synthesis within tissues, and in particular that N-glycolylneuraminic acid (Neu5Gc), not normally found in human tissues, is used for ganglioside synthesis in some cancers. Now there is evidence that dietary control can regulate the expression levels of gangliosides in tissues, and it is hoped that this may helpful in treating ganglioside-related diseases (Okuda, T. Dietary control of ganglioside expression in mammalian tissues. Int. J. Mol. Sci., 21, 177 (2020);  DOI - open access).

If you are stuck at home in isolation because of Covid-19, why not spend a little time browsing through the Lipid Essentials pages (and other web pages) on this site. I am always grateful for feedback - suggestions for improvements, correction of errors, etc - as these pages are not peer reviewed, and like all humankind I am fallible.

March 11th, 2020

I can heartily recommend the personal reflections of Professor Sarah Spiegel (My journey with sphingosine-1-phosphate) that have just been published (Spiegel, S. Sphingosine-1-phosphate: From insipid lipid to a key regulator. J. Biol. Chem., 295, 3371-3384 (2020);  DOI - open access). Aside from being a remarkable account of the discovery of the manifold functions of this key lipid, which has inspired countless new research efforts, it is an enlightening story of how physical and personal difficulties were overcome to accomplish so much seminal work. Reading it caused me to reflect on how women in science have fared during my own research career. At high school in the 1950s, I only encountered two female teachers, who were both unmarried (then the norm), while girls were subtly directed away from the sciences. At University, I was never taught any course by a female lecturer/professor, and in my subsequent post-doctoral research at the Hormel Institute in Minnesota there were no female staff in tenured positions. This was also true for senior positions in my first permanent post at the Hannah Research Institute until the late 1970s. I am not in a position to judge now whether we have a truly level playing field in employment, and I don't suppose that we will be able to make such a judgment until we can discuss someone's research career without making an important issue of their gender.

Incidentally, I also encountered a new review from Spiegel's laboratory on sphingosine-1-phosphate and cancer (Singh, S.K. and Spiegel, S. Sphingosine-1-phosphate signaling: A novel target for simultaneous adjuvant treatment of triple negative breast cancer and chemotherapy-induced neuropathic pain. Adv. Biol. Regul., 75, 100670 (2020); DOI - open access).

Improved analytical methodology invariably leads to novel biological findings, and a new mass spectrometric technique applied to the much-studied gangliosides of human brain has revealed many novel molecular species, including those with up to seven sialylations, and with O-fucosylations and O-acetylations (Ica, R. et al. Orbitrap mass spectrometry for monitoring the ganglioside pattern in human cerebellum development and aging. J. Mass Spectrom., e4502 in press (2020);  DOI.

Two books on lipid biochemical topics have been published by Springer for those with access (not me) - Bioactive Ceramides In Health And Disease: Intertwined Roles Of Enigmatic Lipids. (Ed.: Stiban, J.), Adv. Exp. Med. Biol., Vol. 1159 (2019); and Role Of Bioactive Lipids In Cancer, Inflammation And Related Diseases (Eds.: Honn, K.V. and Zeldin, D.C.), Adv. Exp. Med. Biol., Vol. 1161 (2019).

March 4th, 2020

One of the key unknowns regarding plasmalogen biosynthesis has been identification of the enzyme responsible for introducing the double bond into position 1 of the alkyl chain. This has at last been identified as the orphan human protein designated TMEM189, following the identification of an analogous enzyme in bacteria (Gallego-Garcia, A. et al. A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis. Science, 366, 128-132 (2019);  DOI). Now this opens the way to learning much more of the functions of plasmalogens in tissues. While they may have roles in membrane organization, signalling, and as antioxidants, my impression in that the data in some areas are not as solid as they could be.

I was also greatly interested in a lipidomics paper dealing with ether lipids that show appreciable differences in the nature and concentrations of specific alkyl and alkenyl ethers between centenarians and other age groups (Pradas, I. et al. Exceptional human longevity is associated with a specific plasma phenotype of ether lipids. Redox Biology, 21, 101127 (2019);  DOI). Unfortunately, there does not appear to be any way that I can use this information to my advantage to guarantee another 20 years of this blog.

My apologies if some of the external links from the Lipid Library have not been working correctly in recent weeks, especially DOI addresses. The problem should now have been corrected.

Earlier entries in this blog (older than 4 months) are archived by year as follows -

2020 2019 2018 2017 2016 2015 2014 2013
Author: William W. Christie Updated: July 15th, 2020 Contact/credits/disclaimer LipidWeb logo