The Lipid Library

A LIPID BLOG

An occasional series of notes on publications or other items dealing with lipid science that seem to be of particular interest. Inevitably, my selection is highly subjective.

11/5/08

It is almost axiomatic that sphingolipids only contain very-long-chain saturated and monoenoic fatty acids, sometimes with 2-hydroxyl groups. This simple picture was disrupted when it was observed that sphingomyelin in testes contained polyunsaturated fatty acids, then later it was shown that complex fucolipids in this organ also contained such fatty acids. In relation to the latter class of lipids, a new paper confirms that both the complex carbohydrate moieties and the polyunsaturated fatty acids are essential for spermatogenesis (Rabionet et al. Male germ cells require polyenoic sphingolipids with complex glycosylation for completion of meiosis. A link to ceramide synthase-3. J. Biol. Chem., 283, 13357-13369 (2008)).

5/5/08

Lipid analysis is of value in some surprising circumstances, and three recent papers highlight its value in detecting and monitoring alcohol abuse, either through the determination of phosphatidylethanol or of fatty acid ethyl esters. It seems that living or dead they can find you out via your lipids (Bendroth et al. Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse. Forensic Sci. Int., 176, 76-81 (2008); Gareri et al. Prevalence of fetal ethanol exposure in a regional population-based sample by meconium analysis of fatty acid, ethyl esters. Ther. Drug Monitoring, 30, 239-245 (2008); Pragst and Yegles. Determination of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in hair: A promising way for retrospective detection of alcohol abuse during pregnancy? Ther. Drug Monitoring, 30, 255-263 (2008)).

2/5/08

There have been two papers in the last year on the biochemistry of platelet activating factor, which have added important new information and have caught my eye. Studies with a purified lyso-PAF:acetyltransferase show that with cells in the resting state, the enzyme can utilize arachidonoyl-CoA to produce the membrane-bound PAF precursor 1-alkyl-2-arachidonoyl-glycerophosphocholine with even greater facility than the generation of PAF per se. Only when the cells are subjected to acute inflammatory stimulation does the activated enzyme produce PAF, while simultaneously arachidonate is released for eicosanoid production (Shindou et al. A single enzyme catalyzes both platelet-activating factor production and membrane biogenesis of inflammatory cells. Cloning and characterization of acetyl-CoA:lyso-PAF acetyltransferase. J. Biol. Chem., 282, 6532-6539 (2007)). To complement this work, a novel lyso-PAF acetyltransferase has now been discovered that operates under non-inflammatory conditions, i.e. it is constitutively expressed (Harayama et al. Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor. J. Biol. Chem., 283, 11097-11106 (2008)).

30/4/08

Most so-called 'arsenolipids' are not really lipids by any definition that I would accept. However, two new fatty acids have been isolated from codliver oil, which certainly fit this description. One is a stearic acid analogue (as illustrated) and the other an oleic acid analogue. The authors suggest that the primer molecule in their biosynthesis is dimethyl-arsinoylacetic acid (Rumpler, et al., Arsenic-containing long-chain fatty acids in cod-liver oil: A result of biosynthetic infidelity? Angew. Chem. Int. Ed., 47, 2665-2667 (2008)).

26/4/08

My comments regarding sphingolipids in my last notes, are even more appropriate now. The March issue of Biochimica et Biophysica Acta - General Subjects contains 36 articles under the title “Glycobiology and Sphingobiology”. The lead article is - Hakomori, S.I. Structure and function of glycosphingolipids and sphingolipids: recollections and future trends. Biochim. Biophys. Acta, 1780, 325-346 (2008). I count on such publications to keep my website section ‘All about Lipids’ up-to-date, but I suspect that it will be some time before I can do justice to reading through all of these.

23/4/08

There has been no shortage of review articles dealing with sphingolipids in recent years. Not that I am complaining, as it is encouraging to see how the world is beginning to appreciate the importance of any aspect of lipid metabolism. A substantial new review (Sabourdy et al. Functions of sphingolipid metabolism in mammals - lessons from genetic defects. Biochim. Biophys. Acta, 1781, 145-183 (2008)) appears to offer a good overview of this wide subject.

20/4/08

I have strictly avoided comment on nutritional issues relating to fatty acids on this website, as it has always seemed a potential mine field for the unwary. No sooner do I think I understand some aspect of the problem, that someone publishes a meta analysis or criticizes the statistics or design of the experiments and comes up with the opposite conclusion. That said, I still like to keep up to date in the field and two new review articles are helpful (Harris, W.S., Miller, M., Tighe, A.P., Davidson, M.H. and Schaefer, E.J. Omega-3 fatty acids and coronary heart disease risk: Clinical and mechanistic perspectives. Atherosclerosis, 197, 12-24 (2008); Hadders-Algra, M. Prenatal long-chain polyunsaturated fatty acid status: the importance of a balanced intake of docosahexaenoic acid and arachidonic acid. J. Perinatal Med., 36, 101-109 (2008)).

A further new review paper discusses present knowledge concerning intestinal fat absorption, and the cellular uptake and trafficking of long-chain fatty acids in relation to lipoprotein synthesis. The paper is in French (Petit, V., Niot, I., Poirier, H. and Besnard, P. Fatty acids intestinal absorption: facts and uncertainties. Nutr. Clin. Metabolisme, 21, 38-45 (2007).

15/4/08

To the uninitiated, the title of a recent review article may seem to have little relevance to lipids (Ma, G., Xiao, Y. and He, L. Recent progress in the study of Hedgehog signalling. J. Genetics Genomics, 35, 129-137 (2008)). It certainly has little relevance to small spiky mammals. However, biochemists will recognise that the hedgehog proteins are modified by a covalently linkage to cholesterol, which ensures that they are firmly located in specific membranes where they can carry out their signalling functions. This article provides a useful review of these proteolipids, and provides a reminder of the importance of cholesterol in the proper functioning of animal tissues.

13/4/08

I have only recently become aware of a website - Journalseek - that is extremely useful for locating the websites of scientific journals. It tells you immediately who is the publisher and whether or the journal has a website with online access, while providing a direct link to it.

I have now had an opportunity to browse through the Oily Press book on phospholipids mentioned in my previous contribution, and I am sure it will prove useful to anyone with an industrial interest in phospholipids, with chapters, on "sources, composition and processing", "enzymatic modifications", "use as functional ingredients", "physical properties" and "chemical modifications". However, there are also useful chapters on "biological functions", "clinical and nutritional properties" and "sphingolipids" that will interest a wider audience

9/4/08

The Oily Press have just published a new book - "Phospholipid Technology and Applications", edited by my colleague Frank D. Gunstone (Volume 22 in The Oily Press Lipid Library). Web page: http://www.pjbarnes.co.uk/op/pta.htm

8/4/08

The acidic phospholipids, such as phosphatidic acid and phosphatidylserine have always present problems to chromatographers because of tailing on adsorbents. An interesting new paper appears to have solved the problem for reversed-phase HPLC at least (Ogiso, H., Suzuki, T. and Taguchi, R. Development of a reverse-phase liquid chromatography electrospray ionization mass spectrometry method for lipidomics, improving detection of phosphatidic acid and phosphatidylserine. Anal. Biochem., 375, 124-131 (2008)). The authors use a mobile phase with a very high water content. For example, one component of the gradient used is Isopropanol-methanol-water (5:1:4 by volume) supplemented with 0.2% formic acid, 0.028% ammonia, and 5 µM phosphoric acid. It would be useful now to have a normal phase method that could give sharp peaks for these lipids.

5/4/08

The journal Advanced Drug Delivery Reviews has devoted a special issue (Number 6 of this year) to the topic of “Lipid-based systems for the enhanced delivery of poorly water-soluble drugs”.

2/4/08

Unfortunately I don’t have easy access to ACS publications, but judging by the abstract alone there is an important paper on cholesterol in one of their physical chemical journals (Poyry, S., Rog, T., Karttunen, M. and Vattulainen, I. Significance of cholesterol methyl groups. J. Phys. Chem. B, 112, 2922-2929 (2008)). During evolution. some of the methyl groups have been removed from one face of the molecule to smooth its structure. The authors ask the question whether the remaining methyl groups are necessary, and the answer seems to be undoubtedly yes for various subtle reasons. In particular the C18 methyl group is required for proper orientation of the sterol in membranes.

29/3/08

The March issue of the journal Current Topics in Medicinal Chemistry contains five review articles dealing with the topic of “medicinal chemistry of agents targeting the endogenous cannabinoid system”.

The latest issue of the journal Progress in Lipid Research is now available online. I have yet to check it out in detail, but I note that Dennis Vance and colleagues continue to find something new and interesting to report regarding phosphatidylcholine.

25/3/08

The most recent issue of the Journal of Biological Chemistry contained two publications that were of particular interest to me. The first (Rouzer, C.A. and Marnett, L.J. Non-redundant functions of cyclooxygenases: oxygenation of endocannabinoids. J. Biol. Chem., 283, 8065-8069 (2008)) reviews aspects of the specificity of the cycolooxygenase(COX)-2 enzyme, which will react with neutral lipid substrates, especially the endocannabinoids 2-arachidonoylglycerol and anandamide, in addition to free arachidonic acid to produce esterified prostanoids. These may constitute a new class of lipid mediator.

The second (Zhao, Y. et al. Identification and characterization of a major liver lysophosphatidylcholine acyltransferase. J. Biol. Chem., 283, 8258-8265 (2008)) describes a long-sought enzyme that is involved in the remodelling of newly synthesised phosphatidylcholine to generate the eventual fatty acid composition. The process of lipid remodelling in animal tissues has not received the attention it deserves over the years, but has recently become more intensively studied especially in relation to cardiolipin.

22/3/08

The March issue of the journal Current Opinion In Clinical Nutrition And Metabolic Care contains seven articles under the general title of “Lipid metabolism and therapy”, and edited by Philip C. Calder and Richard J. Deckelbaum.

17/3/08

It is surprising how many new fatty acids continue to be discovered. For example, novel fatty acids containing centrally located five- and six-membered rings with sulfur atoms as part of the structure have been identified by means of gas chromatography-mass spectrometry in garlic (Dembitsky, V.M., Abu-Lafi, S. and Hanus, L.O. Separation of sulfur-containing fatty acids from garlic, Allium sativum, using serially coupled capillary columns with consecutive nonpolar, semipolar, and polar stationary phases. Acta Chromatogr., 19, 206-216 (2007)). I had not come across this journal before, but it is open access.

I have recently found some interesting reports of GC-MS of unusual fatty acids in another open access journal - the Proceedings of the Bulgarian Academy of Science (Comptes rendus de l'Académie bulgare des Sciences).

14/3/08

The October issue (2007) of Seminars in Cell & Developmental Biology is devoted to a series of articles with the general theme of “Membrane lipid microdomains: roles in signalling and disease and 3D chromatin”. The physical chemistry of raft formation from cholesterol and sphingolipids is discussed, together with the role of lipid rafts in signalling.

I admire the Japanese Journal Archive in making so much of the current output of Japanese scientists freely accessible (www.journalarchive.jst.go.jp/). For example, the latest issue of the Tohoku Journal of Experimental Medicine contains two interesting review articles – “Lipid messenger, diacylglycerol, and its regulator, diacylglycerol kinase, in cells, organs, and animals: History and perspective” (Goto, K., Hozumi, Y., Nakano, T., Saino-Saito, S. and Martelli, A.M. Tohoku J. Exp. Med., 214, 199-212 (2008)) – and “Fatty acid binding protein: Localization and functional significance in the brain” (Owada, Y. Tohoku J. Exp. Med., 214, 213-220 (2008)).

9/3/08

I have found a very useful website dealing with lipids and membranes www.cytochemistry.net/Cell-biology/membrane.htm, which I thoroughly recommend.

Membranes have very distinct phospholipid compositions on each leaflet of the bilayer. The means by which this is achieved and then maintained is discussed in a recent review (Lenoir, G., Williamson, P. and Holthuis, J.C.M. On the origin of lipid asymmetry: the flip side of ion transport. Current Opinion Chem. Biol., 11, 654-661 (2007)). In particular, it appears that most of the aminophospholipids are directed to the cytosolic membrane leaflet by means of ATP-fuelled flippases or translocases.

4/3/08

As someone whose best years, physically and mentally, are behind them, I was greatly interested in a recent review by Das (Das, U.N. Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer's disease—But how and why? Prostaglandins, Leukotrienes Essential Fatty Acids, 78, 11-19 (2008)). I will obviously have to study it carefully if I wish to keep up the standards in the ‘Lipid Library’.

The most recent issue of Progress in Lipid Research, now available online, is also largely devoted to polyunsaturated fatty acids and their metabolites. It includes a typically forthright critique of much of the dogma on fatty acid nutrition by Bill Lands (Lands, B. A critique of paradoxes in current advice on dietary lipids. Prog. Lipid Res., 47, 77-106 (2008)). It confirms that my decision to avoid nutritional comments in my own articles here was a sound one.

1/3/08

There is a fascinating paper in the February issue of Lipids that describes a robotic method for transesterifying plasma lipids for rapid GC analysis. The system can handle up to 200 samples per day, so is obviously well suited to large-scale clinical trial. My colleagues and I are rather envious, but the price of the system means that none of us is likely to be replaced by a robot in the near future (Masood, M.A. and Salem, N. High-throughput analysis of plasma fatty acid methyl esters employing robotic transesterification and fast gas chromatography. Lipids, 43, 171-180 (2008)).

27/2/08

I have been advised that the Lipidat web site, dedicated to recording data on the physical properties of lipids, has now moved to a new URL www.lipidat.ul.ie. Unfortunately, it is no longer being updated.

24/2/08

The February issue of Nature Reviews in Molecular and Cell Biology is largely devoted to lipid topics, i.e. ‘Membrane lipids: where they are and how they behave’, ‘Cellular cholesterol trafficking and compartmentalization’, ‘Principles of bioactive lipid signalling: lessons from sphingolipids’, ‘Inositol derivatives: evolution and functions’, and ‘Lipid signalling in disease’. Everyone with an interest in the biochemistry and biological function of lipids will obtain new insights here.

While browsing through the journal mentioned in the previous blog entry, I came across a fascinating recent review on the biological properties of isoprostanes, which I can recommend (Comporti, M., Signorini, C., Arezzini, B., Vecchio, D., Monaco, B. and Gardi, C. F₂-isoprostanes are not just markers of oxidative stress. Free Rad. Biol. Med., 44, 247-256 (2008)).

22/2/08

The biological function of tocopherols has become surprisingly contentious. This may be in part because meta-analyses appear to show that dietary supplements of vitamin E do not protect against atherosclerosis and may even be harmful. I have no intention in joining in this debate. Until recently, it was considered that the only function of tocopherols in animal tissues was to act as antioxidants, but many now consider that this may be secondary to other biological functions. I have therefore enjoyed reading a new review article that is highly relevant to this topic (Atkinson, J., Epand, R.F. and Epand, R.M. Tocopherols and tocotrienols in membranes: A critical review. Free Rad. Biol. Med., 44, 739-764 (2008)). The authors are indeed ‘critical’ and explain the technical difficulties in translating experiments in vitro to the situation in vivo.

Past items will be archived for a few months here..

Last updated: 5/5/2008 Credits/disclaimer	Scottish Crop Research Institute (and MRS Lipid Analysis Unit), Invergowrie, Dundee (DD2 5DA), Scotland