Lipid Matters - A Personal Blog
Or "Lipids Matter". An occasional series of notes on publications or other items dealing with lipid science that seem to be of particular interest to the originator of this web page, Bill Christie. Inevitably, the selection is highly personal and subjective. The older entries are archived for at least a year in a separate web page here..
February 14th, 2018
In plants, glycerolipid biosynthesis in chloroplasts has long been termed the "prokaryotic pathway", and it produces galactosyldiacylglycerols and phosphatidylglycerol with C18 acids in position sn-1 and C16 acids in position sn-2. This pattern is seen in cyanobacteria and it has been assumed that the similarity was a consequence of endosymbiosis during evolution. A new study demonstrates that this is not true (Sato, N. and Awai, K. "Prokaryotic Pathway" is not prokaryotic: noncyanobacterial origin of the chloroplast lipid biosynthetic pathway revealed by comprehensive phylogenomic analysis. Genome Biol. Evolution, 9, 3162-3178 (2017); DOI); the paper is open access. It is now evident that the two steps of acylation in cyanobacteria and chloroplasts utilize enzymes that have no phylogenetic relationship. The structural differences in the diacylglycerol moieties of galactolipids from various species of algae and higher plants originate in fact in compartmentalization of the biosynthetic pathways or precursors in cells, especially between the chloroplasts and endoplasmic reticulum, each compartment having its own distinctive enzymes with characteristic specificities (see my web page on galactosyldiacylglycerols for further discussion).
My prize for the most unusual new lipid that I have encountered this year so far goes to a novel arsenolipid. The unicellular marine alga Dunaliella tertiolecta contains phytyl 5‑dimethylarsinoyl-2-O-methyl-ribofuranoside as 35 to 65% of the total arsenolipids. Apart from its arsenic content, this lipid is unique in containing both an ether-linked phytyl group and a 2‑O‑methylriboside of a type normally found only in RNA. (Glabonjat, R.A. et al. A 2-O-methylriboside unknown outside the RNA world contains arsenic. Angew. Chem.-Int. Ed., 56, 11963–11965 (2017); DOI.
There is an interesting article in Nature on the importance of scientific blogs. Regretfully, they missed this one!
February 7th, 2018
In my blog of two weeks ago, I discussed the therapeutic potential of nitro fatty acids and in particular how subcutaneous injection of nitro-oleic acid suppressed allergic contact dermatitis in mice. Alas, a new publication from the same research group reports that topical applications have the opposite effect (Mathers, A.R. et al. Topical electrophilic nitro-fatty acids potentiate cutaneous inflammation. Free Rad. Biol. Med., 115, 31-42 (2018); DOI). The problem appears to lie in the finding that nitro-conjugated linoleate is formed naturally "in the skin microenvironment as products of cutaneous inflammatory responses and, in high local concentrations, may exacerbate inflammatory skin diseases".
I couldn't have put better the philosophy implied in the title to an editorial contribution to a Nature journal (Marx, V. Fats add structure, they signal, they interact. In the lab, lipids are tough to work with but worth the challenge. Nature Methods, 15, 35-38 (2018); DOI).
I always enjoy reading the personal reminiscences of lipid scientists and that by Dennis E. Vance was no exception, and it has a title that recalls my previous paragraph (From masochistic enzymology to mechanistic physiology and disease. J. Biol. Chem., 292, 17169-17177 (2017); DOI). However, it also served to remind me that a new edition of one of the most valued books in my personal library was now available, but with new editors (Ridgway, N.D. and McLeod, R.S. Biochemistry of Lipids, Lipoproteins and Membranes, 6th Edition. (Elsevier, Amsterdam) (2016) - see Science Direct) - and prompted recourse to Amazon. It covers much the same range of topics as in previous editions, but often with replacement authors, and I expect to make good use of it. As expected with modern textbooks it is very well produced from a technical standpoint. Comparison with the book by Gurr et al. (Lipids: Biochemistry, Biotechnology and Health, 6th Edition), which I reviewed some months ago is probably unfair, as they probably aim at different audiences. My superficial first impression is that the new book goes into the subjects in greater depth but the coverage is not so exhaustive. For example, it was of great help to me in updating my web page on proteolipids, but there is no mention of "endocannabinoids" or "lipid sulfates" in the index.
January 31st, 2018
It has been a puzzle to me how the endocannabinoids, anandamide and 2-arachidonoylglycerol, can have so many different functions in a given tissue while operating through a single G protein receptor. A new review illustrates how this happens using brain as the model (Busquets-Garcia, A. et al. CB1 receptor signaling in the brain: extracting specificity from ubiquity. Neuropsychopharmacology, 43, 4-20 (2018); DOI). It seems that endocannabinoid receptors exert their wide variety of different cellular effects by specific interactions with many other G proteins and that this is dependent on such factors as cell type, subcellular location and cellular functional state. Within a given tissue, expression of a receptor can vary between different locations. For example, in brain some types of neuron contain very high levels of CB1 receptor protein, whereas others have much lower levels; there are even lower levels in some regions of the hypothalamus and astroglial cells. In turn, variation in the location of CB1-interacting proteins may have a role in the cell-specific modulation of endocannabinoid signalling. This paper is part of a special issues on "Cannabinoids and endocannabinoids" and the only one to be open access. However, most of the other contributions appear to be more suitable for specialists.
The number of different molecular species of lipids in a given cell is astonishing (at least 1,000). Yet it is surprising how often only a single molecular species of a given lipid is required for optimum activity in a specific function. Cardiolipin in heart muscle is a prime example. If it had say 10 different fatty acid components, as is usual in most glycerolipids, together with the four different positions for acylation, there could in theory be 104 different molecular species. Instead, as is well known, linoleic acid is by far the most abundant fatty acid (as much as 80%) and the tetralinoleoyl species amounts to at least half the total. Many have speculated as to why this should be so, but a new publication demonstrates that if linoleate is displaced by docosahexaenoate in mitochondrial cardiolipin in the rat then the enzyme activities of the respiratory complexes are greatly reduced, apparently by preventing the formation of phospholipid domains that regulate enzyme activity (Sullivan, E.M. et al. Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome. J. Biol. Chem., 293, 466-483 (2013); DOI). I wonder what would be the result if they tried to displace linoleate with palmitate as this is the most abundant fatty acid in testis cardiolipin and has a much less mobile conformation than DHA.
January 24th, 2018
Nitro fatty acids are fascinating 21st Century molecules with important anti-inflammatory properties (they were first recognized as natural lipid components in 1999). In tissues, they occur in the free form, bound reversibly to thiol-containing proteins and glutathione, and as esters in triacylglycerols and phospholipids. In human serum in addition to non-covalent binding with albumin, nitro-conjugated linoleic acid has been shown to form covalent adducts at Cys-34 (Michael reaction), suggesting that this may be a means of systemic distribution. The effective concentrations of nitro fatty acids in tissues are reduced by this means, but a mechanism for the reversal of the reaction has been revealed under conditions of oxidative stress in vitro in plants at least. Reactive oxygen and nitrogen species, as represented by hydrogen peroxide and peroxynitrite, respectively, have the ability to oxidize cysteine-adducted nitro fatty acids with the release of free nitroalkenes, which can presumably then exert their anti-inflammatory effects (Padilla, M.N. et al. In vitro nitro-fatty acid release from Cys-NO2-fatty acid adducts under nitro-oxidative conditions. Nitric Oxide, Biol. Chem., 68, 14-22 (2017); DOI). Incidentally, nitro fatty acids are present in olives and virgin olive oil at concentrations that may be significant biologically, and it has been argued that they could be one reason for the beneficial effects of the Mediterranean diet. Their clinical potential is under active investigation, for example to inhibit cutaneous inflammation (Mathers, A.R. et al. Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice. Allergy, 72, 656-664 (2017); DOI).
The concept of lipid rafts in membranes, i.e. laterally segregated domains usually enriched in sphingolipids and cholesterol that provide platforms for signalling proteins, is now well established in the scientific literature. The terms termed 'membrane rafts', 'nanodomains' and 'microdomains' tend to be used interchangeably, but a new review suggests that in plants at least, different types of domain exist with differing compositions and functions so more precise definitions are required (Ott, T. Membrane nanodomains and microdomains in plant-microbe interactions. Curr. Opinion Plant. Biol., 40, 82-88 (2017); DOI).
Two substantial review articles deal with the methodology of lipidomics (Rustam, Y.H. and Reid, G.E. Analytical challenges and recent advances in mass spectrometry based lipidomics. Anal. Chem., 90, 374-397 (2018); DOI. And - Hu, T. and Zhang, J.L. Mass-spectrometry-based lipidomics. J. Sep. Sci., 41, 351-372 (2018); DOI). The second of these is open access.
January 17th, 2018
In recent years, I have written to several journals, most recently two months ago, to point out major errors in the interpretation of mass spectra in published papers. On most occasions, the journal has replied promptly and has promised to publish a correction - I still have to see one. Usually, the problem lies in computerized identification of methyl esters of fatty acids, as computers don't recognize that they cannot distinguish between positional and geometrical isomers of monoenoic or dienoic fatty acids, but often the authors (and reviewers) have simply not done their homework. One example, was a report of iso-methyl branched fatty acids in higher plants on the basis of a large ion equivalent to m/z = M-43; it has been known since the 1950s that this is common to mass spectra of all straight-chain fatty acids as a result of a complex rearrangement involving expulsion of carbons 2 to 4.
Problems also arise with interpretation of mass spectra of dimethyloxazoline derivatives of fatty acids. The first authors described a simple rule for how to locate double bonds. However, lacking appropriate standards, they were not aware that the rule did not apply when the double bonds were close to either end of the molecule. In addition, 3-isomers isomerize to 2-isomers on derivatization. The answer is to compare with authentic spectra, such as those on this website. Unfortunately, in spite of my best efforts, there are many flawed publications out there.
The ISI Web of Science seems to be just catching up after the holiday, and my weekly literature seach has given me three special review volumes to digest. I will list selected individual papers in my next literature update, but many of you will wish to consult the original journals for the full list. The December issue of Current Opinion in Plant Biology (Volume 40, Pages 1-168 (2017)) is devoted to the topic of "Cell biology: Membrane dynamics - being at the right place at the right time" (edited by Eugenia Russinova and Karin Schumacher) and includes a number of reviews of interest to plant lipid biochemists. The open access journal Antioxidants (Volume 6, issue 4 (2017)) contains three review articles dealing with tocopherols, including their biosynthesis in plants and their metabolism in humans. The journal Prostaglandins & Other Lipid Mediators (Volume 133, November (2017)) is a special issue from the "6th European Workshop on Lipid Mediators" (edited by Bannenberg, G. et al.) with a number of review articles on polyunsaturated fatty acids and oxylipins (eicosanoids and docosanoids).
January 10th, 2018
Although the most important aspect of any new publication is its content, the manner of presentation can make a big difference to how well the message gets across. Text books have lead the way in this regard, but the ability to use colour in diagrams now afforded by many journals has been a considerable step forward, and as more journals go online only I am sure that this facility will be used increasingly. I am also rather envious of those authors who have access to design departments who produce figures and diagrams that are works of art. One new article that meets all these quality criteria deals with phosphoinositides (Choy, C.H. et al. Phosphoinositide diversity, distribution, and effector function: stepping out of the box. Bioessays, 39, 1700121 (2017); DOI). I found this review to be of considerable value in updating my web page here on the topic.
Some years ago, I was rather pleased with myself when my cholesterol level was measured and found to be in the bottom quartile for my age group, but a friend brought me down to earth by telling me that all this meant was that rather than having a heart attack I would probably die of cancer. The editors' selection (and therefore open access) in the latest issue of JBC explains how two isoforms of phospholipase A regulate the nature of the eicosanoids produced during a heart attack and thence the damage done. In non-failing human hearts, one isoform channels arachidonic acid into protective epoxyeicosatrienoic acids (EETs), whereas in failing hearts, activation of a second isoform channels arachidonic acid into toxic hydroxyeicosatetraenoic acids (HETEs) (Moon, S.H. et al. Heart failure-induced activation of phospholipase iPLA2γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore. J. Biol. Chem., 293, 115-129 (2018); DOI). One way or another your lipids probably get you in the end!
January 3rd, 2018
As a New Year gift to lipid analysts, I draw your attention to a 72 page open access publication reviewing NMR spectroscopy (1H, 13C and 31P) of lipids (Alexandri, E. et al. High resolution NMR spectroscopy as a structural and analytical tool for unsaturated lipids in solution. Molecules, 22, 1663 (2017); DOI). It is a large file at 34Mb, so you may need a fast broadband connection.
The lipid A (endotoxin) component of bacterial lipopolysaccharides is a fascinating complex molecule that serves to protect the organism from attack from external agencies, including antibiotics, but is a major reason for the virulence of pathogenic bacteria. Many factors are involved, including the number and nature of the fatty acid constituents, but the general mechanism of the immune response is usually considered to be a binding to a large hydrophobic pocket in a receptor such as toll-like receptor 4 (TLR4) via the lipid chains, while the phosphate groups can interact directly with the receptor leading to formation of a heterodimer complex that is active in immune signalling. However, a new publication demonstrates that the TLR4 receptor does not recognize the endotoxin of a rather nasty pathogen, Francisella novicida, which is thus able to evade the host innate immune system. Instead, this stimulates the cyclooxygenase-2-dependent inflammatory pathway and is responsible for the lethality of such infections through overproduction of proinflammatory effectors such as prostaglandin E2 (Scott, A.J. et al. Host-based lipid inflammation drives pathogenesis in Francisella infection. PNAS, 114, 12596-12601 (2017); DOI).
The regulation of cholesterol levels in animal tissues is a complicated topic involving innumerable factors, and I struggle to come to grips with it. One novel feature that has just come to light is that the first 100 amino acid in a key enzyme in cholesterol biosynthesis, i.e. squalene monooxygenase, is a proteasomal degradation signal or 'degron'. This sequence attaches reversibly to the ER membrane, and in the presence of excessive cholesterol levels, it is ejected and unravels to expose a hydrophobic patch, which then says "eat me" (Chua, N.K. et al. A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis. J. Biol. Chem., 292, 19959-19973 (2017); DOI).
December 20th, 2017
At this time of year, there is only one paper that I wish to highlight because of its appropriateness to the Christmas season, and happily it is open access (Morikawa, T., Matsuda, H. and Yoshikawa, M. A review of anti-inflammatory terpenoids from the incense gum resins frankincense and myrrh. J. Oleo Sci., 66, 805-814 (2017); DOI). It even has three wise men (persons?) as authors. I presume that the word "anti-inflammatory" in the title refers to "Peace on Earth and goodwill to all men".
Merry Christmas and a happy, healthy, prosperous and anti-inflammatory New Year to all my readers!
December 13th, 2017
In recent years, the potential for using natural lipids as pharmaceuticals to treat various disease states has become very evident. Outsiders such as myself are rarely aware of the many pitfalls in taking a new discovery from patent application through to clinical trials and commercial success. A new review discusses this in relation to palmitoylethanolamide and the specialized pro-resolving mediators (Hesselink, J.M.K. Fundamentals of and critical issues in lipid autacoid medicine: a review. Pain Therapy, 6, 153-164 (2017); DOI). For example, palmitoylethanolamide was proven to alleviate neuropathic pain in the 1990s, but the first company to patent and develop this for clinical purposes went out of business because of delays in the Italian licensing system. Now the patents have expired and there is no financial incentive for anyone else to take it on, although there seems little doubt that it is safe and effective. The first patent on the lipoxins was issued in 1984, but only one clinical pilot trial in atopic eczema can be identified so far.
I take some pleasure in reading of natural cholesterol derivatives with important health-giving properties, and one such is dendrogenin A (DDA), a naturally occurring conjugate of cholesterol and histamine. Its synthesis is greatly reduced in cancer cells, and it has now been shown to be a potent tumor suppressor that controls a nuclear receptor to kill cancers (Segala, G. et al. Dendrogenin A drives LXR to trigger lethal autophagy in cancers. Nature Commun., 8, 1903 (2017); DOI - open access).
There is a report in Nature News that Elsevier continues to have a problem with German universities in that negotiations have failed to end a long-term contract dispute. The aim of the universities, which will no doubt be supported by most scientists, is to reduce subscription prices and promote immediate open access. While I accept that commercial publishers must be allowed to make a profit, the last figure I saw for Elsevier was 36% of turnover and this seems grossly excessive. A new business model is surely required. When I read the report, I checked my personal data base of references that are cited in the Literature Survey section of the LipidWeb, and I found that nearly half were to Elsevier journals. This figure is certainly skewed in that I don't have access to many smaller publishers and many of the chemistry journals, not least those from ACS and RSC, but it does demonstrate the influence of Elsevier. If I can't read papers to update my pages here, I rarely cite them, although I do cite those in journals that are sufficiently public spirited to allow open access after 1-2 years.
December 6th, 2017
Most readers today will not need me to explain the importance of lipid mediators in biology, but this was not always so. I recall attending an ICBL Congress in 1968 when a keynote speaker described prostaglandins as "a drug in search of a disease"! (The only virtue of growing older is that you remember such things). The earliest true pharmaceutical to come into general use and probably still that most widely used is aspirin, which is now known to inhibit the synthesis of the prostaglandins and certain other eicosanoids or modify their nature via its action on the cyclooxygenases. A fascinating new review describes how the full potential of aspirin and many other pharmaceuticals could not have been realized without the knowledge gained from lipidomic studies on the eicosanoid patterns in tissues in various clinical conditions (Stephenson, D.J. et al. Lipidomics in translational research and the clinical significance of lipid-based biomarkers. Translat. Res., 189, 13-29 (2017); DOI). For example, by revealing the pattern of eicosanoids during cardiovascular disease or in patients with pre-eclampsia, it became evident that low-doses of aspirin had great therapeutic potential. Many other benefits from lipidomic studies to such disease states as neurodegenerative diseases, cancer, sepsis and wound healing are discussed also in this review.
The tag "et al." has never been more useful than in a new publication in the Journal of Lipid Research, which has 94 authors (I don't guarantee the accuracy of my count) (Bowden, J.A. et al. Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma. J. Lipid Res., 58, 2275-2288 (2017); DOI). John A. Bowden was fortunate in that his name is first in the alphabetical order of authors so takes pride of place in the list. Joking aside, I suspect that this will come to be regarded as a seminal paper in the science of lipidomics, although it is a pity that it is not open access. However, like me, you may still be able to get hold of a manuscript copy if not the final printed form via the journal.
November 29th, 2017
In plants, the external cuticle layer has many of the same functions as the skin in animals in that it acts to prevent water loss while providing a barrier against pathogenic bacteria and fungi as well as insect predators. Lipids play key roles in both although their natures are very different; in skin, ceramides and other sphingolipids are the essential components, but in plants there is a complex polyester that includes polyhydroxy and dibasic fatty acids and this is overlaid by a layer of wax. While some have argued that plant waxes are the most abundant lipids on earth, it is the polyester component of the cuticle that is attracting most interest at the moment because of its structural properties and the potential to modify it to increase crop yields or as a future source of bio-plastics. Incidentally, cutins from decaying plants are also the source of important lipid components of soils. The Journal of Experimental Botany has devoted a special issue to the topic with an introductory article that summarizes many of the key factors and is open access (Domínguez, E. et al. The plant cuticle: old challenges, new perspectives. J. Exp. Bot., 68, 5251-5255 (2017); DOI).
Among the novel lipids of skin are ceramides containing estolide linked fatty acid constituents. However, it is those with free carboxyl groups or 'FAHFA' (Fatty Acid ester of Hydroxy Fatty Acid) in other tissues that continue to fascinate. A range of (O-acyl)-ω-hydroxy-fatty acids (the hydroxyl group is terminal not centrally located) with up to 52 carbon chain lengths have been found in equine amniotic fluid, together with many other interesting lipid species (Wood, P.L. et al. Lipidomics of equine amniotic fluid: Identification of amphiphilic (O-acyl)-ω-hydroxy-fatty acids. Theriogenology, 105, 120-125 (2018); DOI). Similar fatty acid estolides have been found in sperm and meibomian glands, but their function is still a matter for speculation.
The journal Seminars in Immunology has devoted a special issue (Volume 33, Pages 1-74, October 2017) to the topic of "Leukotriene B4 mediated inflammation" (edited by Bodduluri Haribabu).
November 22nd, 2017
Of all the health food supplements that are available, it appears that omega-3 fatty acids from fish oil preparations are the most popular. While reputable manufacturers take great pains over the quality of their products, they have no control of how they are stored in supermarkets or whether consumers store them properly or simply let them sit in medicine cabinets.· I am sure that oxidation products often develop rapidly, although off-flavours may be disguised by the encapsulation process.·· A new review summarizes the biological properties of compounds derived from peroxidation of omega-3 polyunsaturated fatty acids,· including aldehydes, isoprostanes· and more (Wang, W. et al. Chemistry and biology of ω-3 PUFA peroxidation-derived· compounds. Prostaglandins Other Lipid Mediators, 132, 84-91 (2017); DOI).· Many potential adverse effects are known, and the authors are concerned that variable amounts of such impurities· might explain the mixed results obtained in some nutritional studies. Personally, I prefer fresh fish to fish oil supplements.
S-Palmitoylation is increasingly being seen as an important way· of regulating the activities of potential membrane proteins.· In humans, 23 palmitoyl transferases are known to exist with a conserved cysteine-rich domain containing· a distinctive aspartate-histidine-histidine-cysteine (DHHC) motif, which is required for activity.· On the other hand, no conserved amino acid sequence has yet been identified in target proteins.· A new open access publication describes interesting mass spectrometry methodology to reveal· that there is a random palmitoylation process that depends simply upon the accessible· of cysteines in proteins to the palmitoyl transferases (Rodenburg, R.N.P. et al. Stochastic palmitoylation· of accessible cysteines in membrane proteins revealed by native mass spectrometry. Nature Commun., 8, 1280 (2017);· DOI).
November 15th, 2017
The hedgehog proteins are among my favourite molecules as they stick up two metaphorical fingers to nutritionists. The first such finger is cholesterol, which is covalently bound to the C-terminus, while the second is palmitic acid covalently bound to the N-terminus. Although they are anathema in some quarters, the vital importance of the two much maligned lipid components is clearly demonstrated since hedgehog proteins have a major role in signalling during the differentiation of cells in the development of all embryos from Drosophila to fish to humans and are required for an extensive range of processes, from the control of left-right asymmetry of the body to the specification of individual cell types within the brain and limb development. They are the subject of a new open access review (Blassberg, R. and Jacob, J. Lipid metabolism fattens up hedgehog signaling. BMC Biology, 15, 95 (2017); DOI).
Membrane microdomains termed 'rafts' have long been believed to be formed spontaneously in the outer leaflet of the plasma membrane by the physical chemical association of cholesterol, sphingolipids and membrane proteins. They act to compartmentalize and provide a platform for the last and thereby separate different biochemical functions. However, there is a conflicting view of the prevailing raft hypothesis based on studies by high-resolution secondary ion mass spectrometry that suggests that sphingolipids are concentrated in micrometer-scale membrane domains while cholesterol is evenly distributed within the plasma membrane. In this model, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with cholesterol. An open access review, published earlier this year, discusses this alternative theory (Kraft, M.L. Sphingolipid organization in the plasma membrane and the mechanisms that influence it. Front. Cell Dev. Biol., 4, 154 (2017); DOI).
I was under the impression that I had a good understanding of the nature of bile acids, which are important cholesterol metabolites with essential functions in digestions and signalling. However, I have just come across a paper that describes a small group of bile acids with planar structures of which I had no previous knowledge (Shiffka, S.J. et al. Planar bile acids in health and disease. Biochim. Biophys. Acta, Biomembranes, 1859, 2269-2276 (2017); DOI). These are found in humans during infancy and in a few disease states, but not otherwise. In evolutionary terms, they may be related to the ancestral bile acids.
November 8th, 2017
Another special journal issue deals with the important topic of specialized pro-resolving mediators, i.e. resolvins, protectins and maresins, (Dalli, J. (Editor) The physiology and pharmacology of specialized pro-resolving mediators. Molecular Aspects of Medicine Volume 58, Pages 1-130 (December 2017)). The editor's own contribution is open access and has the intriguing title of "Does promoting resolution instead of inhibiting inflammation represent the new paradigm in treating infections?" Uncontrolled inflammation as occurs during sepsis is an increasing problem in our hospitals, and the resolvins, protectins and maresins have been shown to "actively reprogram the immune response to promote clearance of invading pathogens, and counter-regulate the production of inflammation-initiating molecules". Clinical trials of these lipids and mimetics against a number of inflammatory conditions, including sepsis, are now in progress and they are discussed in other reviews in this issue.
In contrast, cholesterol 5,6-epoxide formed non-enzymatically was for some time believed to be a causitive agent in cancer, but it has now been established that downstream metabolites are in fact responsible (Voisin, M. et al. Identification of a tumor-promoter cholesterol metabolite in human breast cancers acting through the glucocorticoid receptor. PNAS, 114, E9346-E9355 (2017); DOI). A cholesterol epoxide hydrolase converts cholesterol 5,6-epoxide into cholestane-3β,5α,6β-triol, which is transformed by 11β-hydroxysteroid-dehydrogenase-type-2 into the oncometabolite 6-oxo-cholestan-3β,5α-diol. By binding to the glucocorticoid receptor, this last metabolite stimulates the growth of breast cancer cells. It is hoped that targeting the enzymes involved in this metabolic process may lead to new treatments for breast and other cancers.
It has been less easy to establish definitively the biological effects of other oxysterols as so much cholesterol may be present in experiments in vitro that unwanted metabolites may be introduced inadvertently. However, there is good evidence for the involvement of 27-hydroxycholesterol as an endogenous and selective modulator of estrogen receptors with implications for a number of disease states including neurodegenerative diseases, atherosclerosis, osteoporosis and some cancers (He, S.S. and Nelson, E.R. 27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator. Maturitas, 104, 29-35 (2017); DOI).
Every year I seem to find a news item highlighting the poor job prospects for new PhD students and I usually predict that nothing will change. This is still true - see Nature News!
November 1st, 2017
While I have been enjoying the sunshine of the Canary Islands, the world of lipids has been turning rapidly. It seems most unfair that after returning from 30°C on a beach in Gran Canaria to 11°C and thermal underwear in Scotland, in addition to scanning many new research papers and other chores, I have now to try to assimilate three special review volumes to update my Lipid Essentials pages, i.e. "Focus on plasmalogens" in FEBS Letters (Volume 591, Issue 20) and open access, "Oxysterols and Phytosterols in Human Health" (edited by Charbel Massaad, Luigi Luliano and Gérard Lizard) in Chemistry and Physics of Lipids (Volume 207, Part B) and "Microbe and host lipids", edited by Jérôme Nigou, Lhousseine Touqui, Michel Record in Biochimie (Volume 141).
Sometimes it is the science oddities rather than major new research findings in terms of lipid metabolism that catch the eye. For example, I was intrigued by a report in the popular scientific press of preen gland lipids being identified in the fossil of a 48-million-year-old bird. It appears that the composition was sufficiently similar to that of the waxes in modern birds to enable an unequivocal identification.
Another fascinating if more relevant observation in relation to human health is carried in a paper that demonstrates that gangliosides are essential for hearing in that their presence in membrane rafts is required to maintain the structural and functional integrity of hair cells in the ear (Inokuchi, J. et al. Gangliosides and hearing. Biochim. Biophys. Acta, General Subjects, 1861, 2485-2493 (2017); DOI). If you have an interest in these sphingoglycolipids there is a second publication in the same journal issue dealing with gangliosides, rafts and inflammation.
October 18th, 2017
For decades, plant biochemists have been looking for a magic bullet that will enable them to alter the lipid composition of membranes in plants to make them less sensitive to cold. Some progress has been made by introducing desaturase genes, and the composition of phosphatidylglycerol appears to be especially important. However, a new review provides a broader context to the problem by comparing the factors that differentiate the model plant Arabidopsis from a close relative that is especially hardy (Barrero-Sicilia, C. et al. Lipid remodelling: Unravelling the response to cold stress in Arabidopsis and its extremophile relative Eutrema salsugineum. Plant Sci., 263, 194-200 (2017); DOI). It is evident that there are many different factors involved including many compounds other than lipids (sugars, nitrogen compounds and proteins) that are required to conserve membrane integrity during cold acclimatization. Then, we have to understand the role of signalling lipids in controlling how membranes respond to change, where it appears that sphingolipid analogues of sphingosine-1-phosphate are especially important. Despite this complexity, the authors seem to be confident that further lipidomic studies in combination with genome editing in a precise manner "will enable the development of breeding strategies that deliver climate resilient crops."
The nature of the challenges to modifying lipid compositions in plants is illustrated by a further review in the same journal issue, where the authors point out that to introduce new fatty acids of potential industrial interest to crop plants it is rarely possible to introduce a single biosynthetic gene. It is always necessary to add futher genes for enzymes that can handle the new fatty acid and complete the transfer to a safe esterified state (Aznar-Moreno, J.A. and Durrett, T.P. Metabolic engineering of unusual lipids in the synthetic biology era. Plant Sci., 263, 126-131 (2017); DOI).
I suppose it was not really a surprise to learn that Elsevier and the American Chemical Society have filed a lawsuit with the aim of removing copyrighted material from ResearchGate (see Nature News). I have mixed feelings about this, coloured of course by my personal circumstances. My former employer allows me access to a wide range of biological publications from the big three publishers together with a range of journals to which it subscribes, but I can't access chemistry journals or many of those with a medical slant. While I could use interlibrary loan facilities, this bears a significant cost and I cannot justify this when I am only going to use the information I glean for my website and not for research purposes. The prices required by journals for digital access are so unreasonable - far higher than those for interlibrary loan photocopies - that it is no wonder that scientists turn to ResearchGate in the hope of finding copies there. I have to confess that I do this from time to time, and often find preprints rather than the final publications and these are more than adequate for my purposes. Would this be a fair compromise?
As you may guess from the title, I read another review with great interest this week (Bustos, V. and Partridge, L. Good ol' fat: links between lipid signaling and longevity. Trends Biochem. Sci., 42, 812-823 (2017); DOI). While it is a fascinating account of the use of the nematode worm Caenorhabditis elegans in studies of this kind, it is apparent again that there is no magic bullet alas. However, there is clear evidence that dietary restriction helps, and oleoylethanolamide does extend life in worms at least via its signalling properties. There is also something to be said for higher relative dietary proportions of oleate in general. If it will keep me compos mentis as well for longer, I will volunteer as a guinea pig.
Last month, I highlighted a multiauthor paper describing protocols for the use of NMR spectroscopy for the analysis of lipoprotein classes. Now a new review publication provides a general overview of the techniques involved (Aru, V. et al. Quantification of lipoprotein profiles by nuclear magnetic resonance spectroscopy and multivariate data analysis. Trends Anal. Chem., 94, 210-219 (2017); DOI).
October 11th, 2017
Developments in mass spectrometric methodology has turned the analysis of lipids into a new science - lipidomics, but I must confess that I tend to pay relatively little attention to the applications of nuclear magnetic resonance spectroscopy to lipid science. The latter lacks the sensitivity of MS methods, but it can make an invaluable contribution to lipid analysis and structure identifications nonetheless, especially when sample size is not limiting. Indeed, NMR spectroscopy may have advantages in settling stereochemical problems. A new review of the subject is therefore timely (Li, J. et al. Applications of nuclear magnetic resonance in lipid analyses: An emerging powerful tool for lipidomics studies. Prog. Lipid Res., 68, 37-56 (2013); DOI). If the DOI link doesn't work, blame Elsevier.
A new review on the subject of "steryl esters" in BBA reminded me that some years ago when I raised a nomenclatural point with IUPAC-IUB, they rebuked me for using the generic term "cholesteryl esters", which I was told should correctly be termed "cholesterol esters". "Cholesteryl" should be applied only when describing individual lipid species, e.g. cholesteryl palmitate, cholesteryl oleate, etc. Over to you Lipid Maps!
Just has Christmas comes earlier every year in the shops at least, so does the new publishing year roll out earlier. In my literature survey last month, I cited my first 2018 reference! The journal Food Chemistry wins the race every year.
October 4th, 2017
Humans differ from all other animals in that we do not make the sialic acid N-glycolylneuraminic acid (Neu5Gc) for incorporation into gangliosides and glycoproteins. This is believed to have occurred during evolution soon after we diverged from a common ancestor with the great apes and may have had profound implications for the development of the human brain. It could also mean that there might have been a fertility barrier between us and other species of hominids. Proving these conjectures has seemed impossible, but it has now been established that sufficient glycoproteins linked to Neu5Gc are present in intact form in fossil bones to enable determination of its presence. It will be fascinating to see how the story now unfolds. There is a popular account of the research in Science Daily with a link to the original publication for those needing further details.
Just as I was working my way through one special issue, Biochimica Biophysica Acta has brought forward another that deals with "Bacterial Lipids" and edited by Russell E. Bishop; I suspect it will keep me busy updating my web pages here for some time.
A fascinating story has emerged in a new publication that demonstrates how the liver undergoes a metabolic switch to provide fuel for brown fat thermogenesis by producing acylcarnitines. Under cold stimulation, white adipocytes release free fatty acids for acylcarnitine production in the liver to be supplied in the circulation to brown adipose tissue. At the same time, uptake of acylcarnitines into white adipose tissue and liver is blocked (Simcox, J. et al. Global analysis of plasma lipids identifies liver-derived acylcarnitines as a fuel source for brown fat thermogenesis. Cell Metab., 26, 509-522.e6 (2017); DOI). While the quantitative aspects appear to require further work, the process is certainly an elegant one. I don't have access to the original paper yet, but the journal issue contains a commentary or 'preview' that describes the work and is accessible (if you know where to look via Google).
Older entries in this blog are archived for at least a year here..
|Author: William W. Christie||Updated: February 14th, 2018||Credits/disclaimer|