Lipid of the Month
Each month we highlight a lipid of scientific interest. The LIPID MAPS® Lipid of the Month Archive lists lipids highlighted from 2015 - present.
Avocados are undoubtedly a dangerous fruit, with around 50,000 avocado-related knife injuries reported over a 10-year period in the US alone1. But that’s not the only way the avocado plant can harm you. It has been known for a long time that the leaves are toxic to animals, especially to lactating livestock. Necrosis of the mammary gland tissues has been observed in goats and mice and cardiac problems follow eating avocado leaves in a variety of species.
The compound responsible for these effects was identified in 1995 as 1-acetoxy-2R-hydroxy-12Z,15Z-heneicosadien-4-one2, more conveniently termed ‘Persin’ (from the Latin name of the Avocado Persea americana). Persin is a 21-carbon, acetylated fatty alcohol, with two double bonds, a keto and a hydroxyl group along the acyl chain. When chemically synthesised, only the R-hydroxyl form was shown to replicate the toxic effects of avocado leaves.
Many toxins can form the basis of drugs and the effects of persin on mammary gland tissue has attracted attention as a potential therapeutic against breast cancer3, though the absence of literature on this subject in very recent years may suggest such research is no longer active.
Evidently, persin is absent in any significant amount from avocado fruit, otherwise they would be inedible, but next time you cut an avocado, don’t hold it in your hand!
Avocado-related knife injuries: Describing an epidemic of hand injury
Am J Emerg Med 2020
Isolation and identification of a compound from avocado (Persea americana) leaves which causes necrosis of the acinar epithelium of the lactating mammary gland and the myocardium
Nat Toxins 1995
A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells
Mol Cancer Ther 2006
Lipid of the Month Archive
Last month, across the world, people watched the stunning video of NASA’s Perseverance rover as it was lowered to the surface of Mars via the hydrazine-powered rockets of its ‘Skycrane’. It’s main mission: to search for signs of ancient life on the Red Planet. Here on Earth, some of our many forms of life actually produce the rocket fuel hydrazine.
Anammox bacteria, found in the ocean, anaerobic bogs and lakes, and in waste-water treatment plants, oxidise ammonia and nitrate to nitrogen and water, via a hydrazine intermediate. They do so in a lipid-bound compartment called the anammoxosome, the membrane of which contains unique lipids found nowhere else in nature. These molecules, including March’s Lipid of the Month, were first identified in 20021 and contain linearly fused cyclobutane groups called ‘ladderanes’ in their fatty acyl chains.
Ladderane lipids form a very tightly-packed membrane which is much less permeable than ‘normal’ membranes, and probably serves to prevent the highly reactive and toxic hydrazine escaping the anammoxosome, as well as efficiently maintaining a proton gradient for the production of ATP.
Hydrazine powers cranes on Mars, but it is contained by ladders on Earth, showing that biology is incredibly resourceful and the diversity of lipids, seemingly endless. Whether Perseverance will find signs of ancient Martian life remains to be seen, but if it does, what sort of lipids might the Martians have contained?
Linearly concatenated cyclobutane lipids form a dense bacterial membrane
Quite a lot of February’s Lipid of the Month is being injected into people’s arms at the moment. It’s found in both the Pfizer-BioNTech and Moderna vaccines for COVID-19. 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) is a component of the liposome in these vaccines, the vehicle which protects the mRNA encoding the viral spike protein and delivers it into cells for translation.
DSPC is a commonly occurring phospholipid in eukaryotic cell membranes, it has two saturated fatty acyl chains of 18 carbons each and a charged phosphocholine head group. It has been used to study model membranes and liposomes for over forty years, so its physical properties in membranes are very well characterised. Commercially, DSPC is readily available and relatively inexpensive.
In the liposome, DSPC is a structural component, forming a stable lipid bilayer1 which prevents leakage of the nucleic acid cargo. But the liposome is a complex object, the lipids don’t simply form a ‘bubble’ enclosing the mRNA. The structure is much more lipid-filled; lipids within the liposome interact with each other and with the mRNA cargo in addition to forming the outer ‘shell’.2
While these COVID vaccines are novel in that they are the first examples of mRNA vaccines delivered via liposomes, it is not the first case of drug delivery via liposomes in the clinic, and not even the first example of RNA delivery in this way.3 So while these vaccines are a triumph of science, they build on work, including lipid research, that has taken place over decades.
Nanomaterial Delivery Systems for mRNA Vaccines
Structure of Lipid Nanoparticles Containing siRNA or mRNA by Dynamic Nuclear Polarization-Enhanced NMR Spectroscopy
J. Phys. Chem. B 2018
The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs.
Nat. Nanotechnol. 2019
In more northerly locations, January’s lipid of the month is in relatively short supply. 1α,25-dihydroxyvitamin D3, or calcitriol, is the active form of vitamin D, which binds to the vitamin D receptor to regulate transcription of potentially thousands of genes. While classically known to be involved in controlling calcium and phosphate levels in the body, it also plays a role in many other processes, including inflammation, infection, immunity, and some cancers1.
Vitamin D is a secosteroid (the prefix seco- from the latin ‘to cut’ indicating one of the sterol rings is broken) formed from 7-dehydrocholesterol. It’s in short supply in winter because the body needs sunlight to make that cut. Ultraviolet light falling on the skin cleaves a bond (between carbons 9 and 10 in the B ring) to form pre-vitamin D3, which isomerises spontaneously to vitamin D3, also known as cholecalciferol.
Cholecalciferol is the form which is found in vitamin supplements, and in foods such as fatty fish and eggs but it is not yet active. It must first undergo two hydroxylation reactions, one at each end of the molecule. The first reaction takes place in the liver to make 25-hydroxyvitamin D3, or calcidiol. Later, in the kidneys and other tissues, calcidiol has another hydroxyl group added, at the opposite end of the molecule to produce calcitriol.
There has been a great deal of research published over the past year on the link between vitamin D and COVID-19. At the time of writing there were over 300 such articles indexed on PubMed. Whether any effect is specific to this virus, or indicative of general immune health, we may never know. Given the many genes influenced by vitamin D, it’s definitely a complicated question to answer.
Primary Vitamin D Target Genes of Human Monocytes
Front. Physiol. 2019
In A Christmas Carol, Charles Dickens describes Marley’s ghost as having “a dismal light about it, like a bad lobster in a dark cellar.” Written before electric lighting and refrigeration, luminescent lobsters might have been a more commonly observed phenomenon than they are today.
The dismal light of Dickens’ decaying decapod would have been triggered by an acyl homoserine lactone (AHL), December’s lipid of the month.
Several species of bacteria, including Vibrio harveyi, an opportunistic pathogen of shellfish, produce light. Given it’s ecological niche, there would likely be lots of V. harveyi on the surface of a rotting lobster, and it’s only when there are lots in one place that they make light. AHL is used to sense how many bacteria are around using a system known as quorum sensing. Different species make different AHLs, each with specific acyl groups. In the case of V. harveyi, 3-hydroxybutyryl homoserine lactone is it’s calling-card1.
Each bacterium secretes AHL and is able to sense its concentration in the environment. If the bacterium is swimming about in the sea, the AHL quickly gets diluted and as the concentration is very low, no light is produced. As a single bacterium could not make enough light to be detected, doing so would be futile. However, if there are lots of bacteria in one place, the concentration of AHL is increased because they’re all secreting it, and it acts to switch on transcription of the genes needed to generate light. Many bacteria in one place make enough light for the blue-green glow to be visible.
While it may be hard to see the evolutionary advantage in making rotting lobsters glow, species related to V. harveyi form symbiotic relationships with squid and fish, and live in their light-emitting organs where producing light is critical for the symbiosis.
Quorum sensing, far from just prompting bacteria to make the ghostly glow Dickens spoke of, is also critical for other bacterial properties, including many which have practical implications for humans. For example, the pathogen Pseudomonas aeruginosa uses N-(3-oxododecanoyl)homoserine lactone to sense how many of its fellow bacteria are around, which contributes to its virulence2>.
Biosynthesis and stereochemistry of the autoinducer controlling luminescence in Vibrio harveyi
J. Bacteriol. 1993
The Pseudomonas aeruginosa Quorum-Sensing Molecule N-(3-Oxododecanoyl)Homoserine Lactone Contributes to Virulence and Induces Inflammation In Vivo
J. Bacteriol. 2002
Turn the clock back 50 years, and phospholipids were considered solely structural components of cell membranes. However, in the 1970s a compound which caused platelet aggregation, blood clotting, and promoted inflammation was identified. It was named platelet-activating factor (PAF); and in 1979 shown to be a phospholipid 1
PAF is a phospholipid in which the glycerol has an alkyl group, typically of 16 carbons (though this varies) attached via an ether linkage at the sn-1 position. The sn-2 position is occupied by an acetate group while sn-3 position carries the phosphocholine headgroup. It interacts with a specific G-coupled protein receptor to cause some, if not all, of its effects and is active at picomolar concentrations.
PAF can be synthesised in two ways, either the ‘remodelling pathway’ by which it is synthesised from membrane alkyl/acyl phospholipids via the enzyme phoshpolipase A2 which removes the acyl chain at the sn-2 position, forming a lyso-phosphocholine. The sn-2 position is then enzymatically esterified with an acetyl group to form PAF. The other route to its synthesis is the ‘de novo’ route in which the alkylglycerol part is first formed, then the phosophocholine head group is added. Finally the acetyl group is added via the same enzyme as in the remodelling pathway.
Not only is this lipid involved in inflammatory and allergic processes, but it has also been implicated in cancers, and neurodegenerative diseases such as Alzheimers’2. Platelet activating factor does much more than activate platelets and there is doubtless much still to be learnt about this molecule.
Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators)
J. Biol. Chem 1979
Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives
It’s October already and here in the northern hemisphere it is what the poet Keats described as ‘the season of mists and mellow fruitfulness’, which, he said, conspires with the sun to ‘swell the gourd’. October’s lipid of the month is found in, and named after, the gourd (Cucurbitaceae) family of plants, including Halloween and Thanksgiving’s iconic gourd, the pumpkin.
Cucurbitacin B is a particularly widespread cucurbitacin, present in many different plant species. Like other cucurbitacins it is a triterpenoid, a huge family of molecules formed from squalene which also encompasses cholesterol and the steroid hormones. Cucurbitacins often occur modified by sugars. Cucurbitacin B glucoside (LMST01010408), where a glucose is linked at the 2-position (the hydroxyl group towards the bottom left of the image) is also called arvenin I as it was first discovered in Anagallis arvensis- not a gourd but a primrose1.
Many cucurbitacins have a bitter taste, indeed arvenin I is described as ‘strongly bitter’, and are likely produced as a defense to try and prevent the plant (and the pumpkin) being eaten. Ironically, some of these taste properties appeal to humans, so the very things designed to protect, actually encourage us to eat them. Of course this is still beneficial for the plant, as human cultivation ensures success for a species.
Various pharmacological properties have been ascribed to Cucurbitacin B, including anti-inflammatory and anti-cancer properties against several different tumour types, such as those in the liver 2. It has even been reported to protect memory in a mouse-model of Alzheimers’ disease3.
So while LIPID MAPS is in no way giving you medical advice, remember if you’re making a pumpkin pie, carving a pumpkin lantern, or maybe both, there’s more to a pumpkin than a wholesome meal and seasonal fun.
Isolation and structures of arvenins from Anagallis arvensis L. (Primulaceae). New cucurbitacin glucosides
Chem Pharm Bull (Tokyo) 1978
Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration
Cancer Letters 2010
Cucurbitacin B induces neurogenesis in PC12 cells and protects memory in APP/PS1 mice
Cell Mol Med 2019
Absentmindedly crush a leaf while out on a country walk and you are likely to set up a whole cascade of reactions within the plant. One of them results in the formation of Arabidopside A1, a member of the arabidopside family of plant oxylipins discovered in the model plant, Arabidopsis thaliana.
The major lipids in plant membranes, particularly membranes of the chloroplast, are galactolipids, a glycerol esterified by two acyl chains and with a galactose sugar as the polar group. The arabidopsides are galactolipids produced in response to plant wounding or infection 2. They are characterised by the presence of oxophytodienoic acid and/or dinor-oxophytodienoic acid as the acyl chains. Arabidopside A contains both of these species, the former at the sn1 position, and the latter at sn2. Phytodienoic acids are known plant hormones in their own right and precursors of the well known plant hormone jasmonic acid. They are chemically similar to the mammalian inflammatory signalling molecules, the prostaglandins.
Exactly how the arabidopsides function isn’t really known, it’s been suggested that they are reservoirs of phytodienoic acids which can be released when needed, but that doesn’t explain why their concentration increases when a plant is wounded. Just imagine how much arabidopside you might cause a plant to make when you mow the lawn!
Arabidopsides A and B, two new oxylipins from Arabidopsis thaliana
Tetrahedron Letters 1993
Wounding Stimulates the Accumulation of Glycerolipids Containing Oxophytodienoic Acid and Dinor-Oxophytodienoic Acid in Arabidopsis Leaves
Plant Physiology 2006
Coprostanol, August’s lipid of the month, is used as a biomarker indicating the presence of sewage in the environment. It is formed by gut bacteria which reduce dietary cholesterol to produce coprostanol, a highly water-insoluble molecule which, in anaerobic conditions, can be stable for thousands of years. This means that coprostanol is not only useful to monitor modern cases of sewage contamination, but can also be used as an indicator of the presence of sewage in archaeological sites. Its very poor water solubility means that any coprostanol in a sample is likely to have originated within the sample, rather than have been deposited from contaminated water flowing through the area over time.
Just as cholesterol is reduced to coprostanol, other dietary sterols are reduced to their respective stanols by gut bacteria. The plant-based diet of ruminant animals results in more faecal stigmastanol, produced from sitosterol. Stanol biomarker ratios therefore can be diagnostic of the species of the faeces.
A recent study in Science Advances analysed stanol biomarkers in 12400 year old coprolites (fossilised excreta) found in an Oregon cave. DNA evidence had previously suggested these were human in origin, but a question of contamination with modern DNA remained. Because coprostanol is not able to seep over time into a sample through contaminated water, and contamination during analysis is extremely unlikely (unless you’re doing science really badly!), the ratio of coprostanol to other sterols in the sample confirmed them to be “unequivocally” human in origin. This research adds to the body of knowledge and the debate surrounding the first human settlement of the Americas.
The origin of faeces by means of biomarker detection
Environment International 2002
Pre-Clovis occupation of the Americas identified by human fecal biomarkers in coprolites from Paisley Caves, Oregon
Science Advances 2020
July’s lipid of the month, chaulmoogric acid, is an ingredient in the first effective leprosy treatment. Found in the seeds of the chaulmoogra tree (Hydnocarpus wightianus), it’s an unusual fatty acid containing a cyclopentenyl group which is thought to act as a biotin mimic, though its mode of action isn’t really known.
Chaulmoogra oil had been used for centuries as an ointment to treat leprosy, but the viscous, insoluble and noxious substance was unsuitable for internal treatment. Alice Ball, a pharmaceutical chemist at the University of Hawaii solved that by developing a method of solubilising the (presumed) active ingredients of chaulmoogra oil, chaulmoogric acid and the related hydnocarpic acid, in useful quantities. Ball’s method was essentially saponification to release the fatty acids from triglycerides and then esterification.
Born in July 1892, Ball died aged only 24, before her method could be published and before she could know how effective it was. The work was continued, with no reference to Ball, by Arthur Dean, the preparation of Chaulmoogra oil becoming known as ‘Dean derivatives’. A review by Harry T Hollmann in 1922 attempted to set the record straight. Hollmann, a doctor at Kalhihi hospital in Hawaii where leprosy patients were sent, had invited Ball to look into producing a soluble chaulmoogra oil derivative. In the review he explains how Ball, the first woman, and first African American to receive a Masters degree from the College of Hawaii, developed the process of producing ethyl esters of chaulmoogra oil. Under the name ‘Dean derivatives’, these were credited with curing 78 patients at the Kalhihi hospital, who were discharged “no longer a menace to society”. Alice Ball’s preparation remained the treatment for leprosy until the advent of antibiotics in the 1940s.
You can read more about Alice Ball in Brianna Bibel’s excellent blog, ‘The Bumbling Biochemist’
The Fatty Acids Of Chaulmoogra Oil In The Treatment Of Leprosy And Other Diseases
Arch Derm Syphilol. 1922
Treatment Of Leprosy With The Dean Derivatives Of Chaulmoogra Oil
Fatty acid esters of hydroxyl fatty acids (FAHFAs, or estolides) are a fairly recent addition to the known mammalian lipidome. They were described in 2016 as a class of lipids with both anti-diabetic and anti-inflammatory effects . Given the combinatorial possibilities of linking a fatty acid with a further hydroxylated fatty acid, where the hydroxyl could be anywhere along the chain, the FAHFA family has potential to be vast.
One example, the linoleic acid ester of 13-hydroxylinoleic acid (13-LAHLA) has been shown to have anti-inflammatory effects. It suppresses expression of genes involved in inflammation such as interleukins 6 and 1beta. It also suppresses expression of cyclooxygenase 2, an enzyme in the prostaglandin synthesis pathway and the target of the commonly used drug ibuprofen.
While it is known that some FAHFAs are ligands for G-protein coupled receptors, their precise mechanism of action, and indeed the full extent of the family, remains to be worked out. There is still much work to be done.
Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects
Cell October 2014
Linoleic acid esters of hydroxy linoleic acids are anti-inflammatory lipids found in plants and mammals
J.Biol.Chem May 2019
Sterol lipids function as hormones across a wide range of species and can have a dramatic effect on the morphology of an individual. 20-Hydroxyecdysone is one such sterol hormone which controls skin-shedding and body pattern in arthropods such as crabs and insects. Its effects on an individual can be dramatic.
A recent paper  from Antonia Monteiro’s lab showed 20-Hydroxyecdysone to have a pivotal role in controlling the size of ‘eye spots’ on the wings of the African butterfly Bicyclus anynana. Adults which emerge from their pupae in the wet season have large eyespots on their wings but those which reach adulthood in the dry season, lack eye spots and are a more dull brown colour.
This difference is determined by the temperature experienced by the caterpillar over two specific days of its life, just before it pupates. While many species show a difference in levels of 20-Hydroxyecdysone depending on temperature, Monteiro showed that in B. anynana, cells in the centre of what would become the eyespot contained the 20-Hydroxyecdysone receptor, making them very sensitive to the hormone.
20-Hydroxyecdysone is not just made by arthropods. Some plants also produce this hormone, presumably as a defence mechanism, disrupting the development of insects grazing on them.
Origin of the mechanism of phenotypic plasticity in satyrid butterfly eyespots
eLife February 2020
Humans are unable to synthesise linoleic acid, and so we must obtain it through the food we eat. Linoleic acid was discovered to be essential in the diet by Mildred and George Burr, working at the University of Minnesota in 1930. They showed that fats were not simply of calorific value but some, including linoleic acid, were absolutely required for health.
Linoleic acid is an 18-carbon fatty acid with two double bonds and present in large amounts in many vegetable oils. It’s one of those polyunsaturated fats which the adverts tell us are good for us.
It’s a precursor to arachidonic acid, which in turn is a precursor to a great many lipidic signalling molecules in the body. A study published in January 2019 looked at the effect of coronavirus infection on cellular lipids and showed that linoleic to arachidonic acid metabolism was “the most perturbed pathway” on infection of cells in their model system.
On the nature and role of the fatty acids essential in nutrition
J. Biol. Chem. January 1930
Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication.
Viruses 2019, 11(1), 73
Ergosta-5,7,22E-trien-3β-ol ( Ergosterol ) is a sterol found in cell membranes of fungi and protozoa, but not animals. The common name, "ergosterol", of this lipid is derived from the group of fungi from which it was first isolated — "ergot" fungi, of genus Claviceps.
The role of ergosterol in fungi is similar to that of cholesterol in animal cells and ergosterol is essential to their survival. Ergosterol is synthesized from lanosterol and several anti-fungal drugs work by targeting erogsterol — either by binding to it, resulting in devastating cellular leakage, or preventing the synthesis of ergosterol from lanosterol.
9-oxo-11R,15S-dihydroxy-5Z,13E-prostadienoic acid(PGE2) is an oxytocic prostaglandin. PGE2's synthetic equivalent, the drug "dinoprostone", is commonly administered during childbirth — to induce labor by stimulating uterine contraction; to promote cervical ripening; and to control postpartum hemorrhage (PPH). PGE2 has also been shown to be involved in stem cell development via modulation of the Wnt pathway.
Nobiletin: efficient and large quantity isolation fromorange peel extract
Biomed. Chromatogr 20: 133 –138 (2006)
Nobiletin restoring beta-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats.
Neurosci Lett. 2006 Jun 12,400(3):230-4. Epub 2006 Apr 3.
Nobiletin and Derivatives: Functional Compounds from Citrus Fruit Peel for Colon Cancer Chemoprevention
Cancers 2019, 11(6), 867
The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK
J. Lipid Res. First Published on January 21, 2020
4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid (DHA) - Fatty Acids and Conjugates [FA01]-> Unsaturated fatty acids [FA0306] - is a long-chain omega-3 polyunsaturated fatty acid [PUFA] commonly found in brain and retina[1,2]. DHA is thought to play a critical role in brain developent, to be involved in multiple aspects of cardiovascular function, and is implicated in multiple diseases and developmental disorders when deficient[1,3].
While DHA levels can be measured using isotope tracers, recent research demonstrates that it can be measured by natural abundance carbon isotope ratio analysis, which is less costly and generally safer.
Essential Fatty Acids: the Importance of n-3 Fatty Acids in the Retina and Brain
Nutrition Reviews Volume 50, Issue 4, April 1992, Pages 21–29
Essential role of docosahexaenoic acid towards development of a smarter brain
Neurochem Int 2015 Oct;89:51-62. Epub 2015 Aug 28
Omega-3 fatty acids EPA and DHA: health benefits throughout life
Adv Nutr 2012 Jan;3(1):1-7. Epub 2012 Jan 5
Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis
Journal of Lipid Research January 2020, 61, 116-126
5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-Oxo-ETE) — Eicosanoids [FA03] -> Hydroxy/hydroperoxyeicosatetraenoic acids [FA0306] — is a G-protein-coupled receptor (GPCR)1 metabolite of the Arachadonic Acid Cascade2 involved in both autocrine and paracrine signaling. 5-Oxo-ETE is thought to be involved in inflammation3 and recent research suggests that it may play a role in the disorder granulomatosis with polyangiitis4.References
- International Union of Pharmacology XLIV. Nomenclature for the Oxoeicosanoid Receptor. Pharmacological Reviews March 2004, 56 (1) 149-157. DOI: 10.1124/pr.56.1.4
- Biochemistry, biology and chemistry of the 5-lipoxygenase product 5-oxo-ETE. Prog Lipid Res. 2005 Mar-May;44(2-3):154-83. Epub 2005 Apr 20. DOI: 10.1016/j.plipres.2005.04.002
- 5-Oxo-6,8,11,14-eicosatetraenoic acid induces the infiltration of granulocytes into human skin Journal of Allergy and Clinical Immunology October 2003 Volume 112, Issue 4, Pages 768–774 DOI: 10.1016/S0091-6749(03)01888-8
- LTB4 and 5-oxo-ETE from extracellular vesicles stimulate neutrophils in granulomatosis with polyangiitis. J Lipid Res. 2019 Nov 18. pii: jlr.M092072. doi: 10.1194/jlr.M092072. [Epub ahead of print] DOI: 10.1194/jlr.M092072
27-hydroxy-cholesterol is a sterol lipid metabolite of cholesterol1 that has been found to be involved in many biological functions, including metastasis of breast cancer2 and alzheimer's disease3. 27-hydroxy-cholesterol has also recently been shown to be present in human breast milk — at a notably elevated concentrations in colustrum — possibly serving an important role in shielding newborn babies from rotavirus and rhinovirus infection4.
- LIPID MAPS® WikiPathways: Cholesterol metabolism
- 27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology Science. 2013 Nov 29; 342(6162): 1094–1098. DOI: 10.1126/science.1241908
- A Crosstalk Between Brain Cholesterol Oxidation and Glucose Metabolism in Alzheimer's Disease. Front Neurosci. 2019 May 31;13:556. DOI: 10.3389/fnins.2019.00556
- Antiviral oxysterols are present in human milk at diverse stages of lactation The Journal of Steroid Biochemistry and Molecular Biology Volume 193, October 2019, 105424 DOI: 10.1016/j.jsbmb.2019.105424
N-Arachidonoyl dopamine or NADA is a fatty acyl that belongs to the fatty amide class and fatty acyl amine sub class. It is an endogenous lipid that is found primarily in brain tissue in mammals1. Due to its structural similarity to N-acyl ethanolamines, NADA may also function as endocannabinoid2 and plays a regulatory role in both the peripheral and central nervous systems, and shows antioxidant and neuroprotectant properties 2. NADA, as ligand of the endocannabinoid receptor system, is involved in all aspects of mammalian physiology and pathology, and for this reason it represents a potential target for the design and development of new therapeutic drugs 3.References:
- Endocannabinoids and endocannabinoid-related mediators: Targets, metabolism and role in neurological disorders. Fabio Arturo Lannotti, Vincenzo Di Marzo and Stefania Petrosino. Progress in Lipid Research. Volume 62, April 2016, Pages 107-128. https://doi.org/10.1016/j.plipres.2016.02.002
- The Endocannabinoid/Endovanilloid N-Arachidonoyl Dopamine (NADA) and Synthetic Cannabinoid WIN55,212-2 Abate the Inflammatory Activation of Human Endothelial Cells. Kevin Wilhelmsen, Samira Khakpour, Alphonso Tran, Kayla Sheehan, Mark Schumacher, Fengyun Xu. Journal of Biological Chemistry. Volume 289, Issue 19 pp.13079–13100. https://doi: 10.1074/jbc.M113.536953 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036321/
- N-Arachidonoyl Dopamine: A Novel Endocannabinoid and Endovanilloid with Widespread Physiological and Pharmacological Activities. Urszula Grabiec and Faramarz Dehghani. Cannabis and Cannabinoid Research. Volume 2, Issue 1, 2017, pp. 183-196. Doi: 10.1089/can.2017.0015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627668/
Cortisol or 11β,17,21-trihydroxypregn-4-ene-3,20-dione (LMST02030001) is a sterol lipid member of the class of steroid hormones known as glucocorticoids. It is produced by the adrenal glands and regulated by the hypothalamus and pituitary in humans, and many other animals1. It is well known for helping our body’s “fight-or-flight” instinct in a crisis2, but it is also important for many other physiological processes such as: regulating blood pressure and the use of nutrients (carbohydrates, fats, and proteins2,3, preventing inflammation4, increasing glucose levels4, controlling the sleep cycle and balancing energy in order to handle stress3,5. Cortisol depletion or excess affects the body’s functions and can lead to many health problems if not monitored regularly5.References:
- The use of hair cortisol for the assessment of stress in animals. Susen Heimbürge, Ellen Kanitz and Winfried Otten. General and Comparative Endocrinology. Volume 270, 2019, pp. 10-17. https://doi.org/10.1016/j.ygcen.2018.09.016
- Investigating associations between momentary stress and cortisol in daily life: What have we learned so far? Wolff Schlotz. Psychoneuroendocrinology. Volume 105, 2019, pp. 105-116. doi.org/10.1016/j.psyneuen.2018.11.038. https://www.sciencedirect.com/science/article/pii/S0306453018306498
- Exercise, the diurnal cycle of cortisol and cognitive impairment in older adults. J. Tortosa-Martínez, C. Manchado, J. M. Cortell-Tormo and I. Chulvi-Medrano. Neurobiology of Stress. Volume 9, November 2018, Pages 40-47. https://www.sciencedirect.com/science/article/pii/S2352289518300109
- Fructose-induced inflammation and increased cortisol: A new mechanism for how sugar induces visceral adiposity. James J. DiNicolantonio, Varshil Mehta, Neema Onkaramurthy and James H. O'Keefe. Progress in Cardiovascular Diseases. Volume 61, Issue 1, 2018, pp. 3-9. https://www.sciencedirect.com/science/article/pii/S0033062017301627
- Redefining neuroendocrinology: Epigenetics of brain-body communication over the life course. Bruce S. McEwen. Frontiers in Neuroendocrinology. Volume 49, 2018, pp. 8-30. Doi.org/10.1016/j.yfrne.2017.11.001. https://www.sciencedirect.com/science/article/pii/S0091302217300687
α-N-(3-hydroxyhexadecanoyl) L-ornithine(LMFA08020242) is an ornithine lipid (OL) that belongs to the fatty acyl category, fatty amide class and N-acyl amine sub-class. OL do not contain either glycerol or phosphate1,3 in their chemical structure and are found in many biological species such as mammals, plants and bacteria2. α-N-(3-hydroxyhexadecanoyl) L-ornithine in particular could be hydroxylated by hydroxylases to form much larger analogous forms3. This particular phenomena, that happens in some bacterial species, is considered a stress response to changing environmental conditions occurring in the membrane (e.g. phosphate-limiting growth conditions, high temperature or acid tolerance)1 that results in simply modifying already existing lipids without the need to synthesize new ones.References:
- Characterization of Ornithine and Glutamine Lipids Extracted from Cell Membranes of Rhodobacter sphaeroides. Xi Zhang, Shelagh M. Ferguson-Miller and Gavin E. Reid. Journal of the American Society for Mass Spectrometry. Volume 20, Issue 2,2009, 198-212. https://doi.org/10.1016/j.jasms.2008.08.017
- The LipidWeb: Simple N-Acylamides and Lipoamino Acids. https://www.lipidmaps.org/resources/lipidweb/index.php?page=lipids/simple/lipamino/index.htm
- Ornithine lipids and their structural modifications: from A to E and beyond. Miguel A. Vences-Guzman, Otto Geiger and Christian Sohlenkamp. FEMS Microbiology Letters. Volume 335, 2012, pp. 1–10. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1574-6968.2012.02623.x
Fucoxanthinol(LMPR01070055) is a prenol lipid that belongs to the isoprenoid class and tetraterpenoid sub-class in LIPID MAPS®. It is also a type of carotenoid found typically in algae, higher plants and photosynthetic bacteria 1. In mammals, fucoxanthinol is obtained from metabolism of fucoxanthin by digestive enzymes (hydrolysis) in the gastrointestinal tract. This is then absorbed directly in the intestine and transported into the circulation and the liver2. Fucoxanthinol has been proposed to have beneficial characteristics such as antioxidant, anticancer, anti-obesity, antidiabetic, and anti-photo-aging properties1,3.References:
- Takashi Hashimoto, Yoshiaki Ozaki, Masashi Mizuno, Masaru Yoshida, Yosuke Nishitani, Takeshi Azuma, Akitoshi Komoto, Takashi Maoka, Yuka Tanino and Kazuki Kanazawa. Pharmacokinetics of fucoxanthinol in human plasma after the oral administration of kombu extract. British Journal of Nutrition. Volume 107, Issue 11, 2012 , pp. 1566-1569 https://doi.org/10.1017/S0007114511004879
- Peipei Sun, Chi-Chun Wong, Yuelian Li, Yongjin He, Xuemei Mao, Tao Wu, Yuanyuan Ren and Feng Chen. A novel strategy for isolation and purification of fucoxanthinol and fucoxanthin from the diatom Nitzschia laevis. Food Chemistry. Volume 277, 30 March 2019, Pages 566-572. https://doi.org/10.1016/j.foodchem.2018.10.133
- Luc J. Martin. Fucoxanthin and Its Metabolite Fucoxanthinol in Cancer Prevention and Treatment. Mar Drugs. Volume 13, Issue 8, pp. 4784–4798. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557004/
Arachidonic acid (LMFA01030001) or 5Z,8Z,11Z,14Z-eicosatetraenoic acid is an unsaturated fatty acid that can be found in plasma membranes where it is esterified to phospholipids (especially phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositols)1,2. Arachidonic acid (AA) and its metabolite by-products (eicosanoids) are important mediators of physiological processes, and these include prostaglandins, prostacyclin, thromboxane, and leukotrienes1,2,3,4. Arachidonic acid is obtained from food or by desaturation/chain elongation of the plant-rich (i.e. green and red algae) essential fatty acid, linoleic acid2,4.References:
- Neurobiology of Brain Disorders. Biological Basis of Neurological and Psychiatric Disorders. Book 2015 Pathobiology of CNS Human Immunodeficiency Virus Infection. Jennifer L. Lyons, Luis B. Tovar-y-Romo, Kiran T. Thakur, Justin C. McArthur and Norman J. Haughey. Pages 444-466. https://www.sciencedirect.com/topics/neuroscience/arachidonic-acid
- Encyclopaedia of Food Sciences and Nutrition. Prostaglandins and Leukotrienes. S. Katayama and J. B. Lee. (Second Edition). 2003, Pages 4798-4804. https://www.sciencedirect.com/topics/neuroscience/arachidonic-acid
- Arachidonic acid: Physiological roles and potential health benefits – A review. Hatem Tallima and Rashika El Ridi. Journal of Advanced Research. Volume 11, May 2018, Pages 33-41. https://www.sciencedirect.com/science/article/pii/S2090123217301273
- A review on algae and plants as potential source of arachidonic acid. Sanaa M. M. Shanab, Rehab M. Hafez and Ahmed S. Fouad. Journal of Advanced Research. Volume 11, May 2018, Pages 3-13. https://www.sciencedirect.com/science/article/pii/S2090123218300389
17β-Estradiol (LMST02010001) is a sterol lipid classified as a C18 steroid estrogen in LIPID MAPS®. It is the most potent type of the four existent estrogens (also known as E2)1 and it is produced within the follicles of the ovaries and therefore considered as the most important female hormone that regulates menstrual cycles and reproduction. 17β-estradiol can be found in other tissues including the testicles, adrenal glands, fat, liver, breasts and brain1,2,3 and in other species such as crustaceans, insects and fish4. Its synthetic form has been widely used for menopause and hormonal disbalance treatments1,3. However, when disposed through wastewater discharges to natural environments like rivers and ponds, and found in large concentrations it could alter the aquatic ecosystem4.References:
- The structural biology of oestrogen metabolism. Mark P. Thomas and Barry V.L. Potter. Journal of Steroid Biochemistry & Molecular Biology. Volume 137 (2013) pp. 27–49. https://www.sciencedirect.com/science/article/pii/S0960076012002749
- PubChem Estradiol (Compound) https://pubchem.ncbi.nlm.nih.gov/compound/estradiol#section=CAS
- Follicle-stimulating hormone promotes the transformation of cholesterol to estrogen in mouse adipose tissue. Huanxian Cui, Guiping Zhao, Jie Wen and Weiming Tong. Biochemical and Biophysical Research Communications. Volume 495, Issue 3, 15 January 2018, Pages 2331-2337. https://www.sciencedirect.com/science/article/pii/S0006291X17325202
- Pharmaceuticals in freshwater aquatic environments: A comparison of the African and European challenge. Samuel Fekadu, Esaya Alemayehu, Raf Dewil and Bart Van der Bruggen. Science of The Total Environment. Volume 654, March 2019, Pages 324-337. https://www.sciencedirect.com/science/article/pii/S0048969718344243
Testosterone is a sterol lipid classified as a C19 androgen. It is excreted by testicular Leydig cells in males (1,2) and plays and important role in sexual development, body composition (bone mass, fat distribution, muscle mass and strength) and regulating general health and wellbeing (1,2,3). As a natural hormone, it is found in males and females but at different concentrations (7:1 male to female ratio). In men, testosterone decreases with age, and in younger males, a clinical deficit can be treated with a drug version (3). For many years, controversy on whether high or low levels of testosterone are related to prostate cancer has been a topic of much discussion and more research is required to provide a better picture on the real causes of developing this disease (1,3,4).References:
- Role of androgens in energy metabolism affecting on body composition, metabolic syndrome, type 2 diabetes, cardiovascular disease, and longevity: lessons from a meta-analysis and rodent studies. Naoki Harada. Journal of Bioscience, Biotechnology, and Biochemistry. Volume 82, 2018 - Issue 10. Pages 1667-1682.
- Understanding How Testosterone Affects Men
- Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies. Eleanor L. Watts, Paul N. Appleby, Aurora Perez-Cornago, H. Bas Bueno-de-Mesquita, June M. Chan, Chu Chen, Barbara A. Cohn, Michael B. Cook, Leon Flicker, Neal D. Freedman, Graham G. Giles, etc. European Urology. Volume 74, Issue 5, November 2018, Pages 585-594.
- The testosterone conundrum: The putative relationship between testosterone levels and prostate cancer. Kevin R. Loughlin. Urologic Oncology: Seminars and Original Investigations. Volume 34, Issue 11, November 2016, Pages 482.e1-482e4.
4-Dimethylarsenoyl butanoic acid also known as DMAB is an organometallic fatty acid that can be found in human urine as a metabolite of larger arsenolipids species containing up to 20 carbons and consumed in seafood (1,3). Exposure to soluble inorganic forms of arsenic has been widely reported as highly toxic and its consumption through drinking water is linked to chronic human health problems including cancer (skin and bladder)(1). Over the last 30 years over 40 naturally occurring water and fat soluble organo-arsenicals such DMAB have been identified in fish, algae and crustaceans at very high concentrations (over 100 µgAs/g of wet mass)(1-4). Although the majority of DMBA and other arsenolipid metabolites are excreted through urine after consumption (85%), their toxicity and fate of the residual amount of arsenic content in the body remains unknown(1,4).References:
- Arsenic Fatty Acids Are Human Urinary Metabolites of Arsenolipids Present in Cod Liver. Ernst Schmeisser, Alice Rumpler, Manfred Kollroser, Gerald Rechberger, Walter Goessler and Kevin A. Francesconi. Angewandte Chemie International Edition. Volume 45, Issue 1, December 16, 2005, pp. 150-154.
- Chronic health effects in people exposed to arsenic via the drinking water: dose–response relationships in review. Takahiko Yoshida, Hiroshi Yamauchi and Gui Fan Sun. Toxicology and Applied Pharmacology. Volume 198, Issue 3, 1 August 2004, pp. 243-252.
- Arsenolipids in marine oils and fats: A review of occurrence, chemistry and future research needs. Veronika Sele, Jens J. Sloth, Anne-Katrine Lundebye, Erik H. Larsen, Marc H. G. Berntssen, Heidi Amlund. Food Chemistry. Volume 133, Issue 3, 1 August 2012, Pages 618-630.
- Arsenic species in seafood: Origin and human health implications. Kevin A. Francesconi. Pure Applied Chemistry. Volume 82, No. 2, 2010. pp. 373–381. doi:10.1351/PAC-CON-09-07-01.
R-(-)-Linalool is a prenol lipid found naturally in many flowers and spices. Prenol lipids are known as terpenoids which are one of the largest groups of naturally occurring compounds synthesised by plants (1,3). (-)-Linalool is one of the major constituents of lavender (Lavandula angustifolia) and coriander (Coriandrum sativum L.) essential oils. Similar to other terpenoids such geraniol (geraniol) and citronellol (citronellol), (-)-Linalool has been reported to have bioactive properties in vitro and in vivo (3), including anti-inflammatory, antifungal, antimicrobial, anti-depressive (2,3), anticancer, antinociceptive, analgesic, anxiolytic and neuroprotective (3). These properties are being commercially exploited by several industries including agronomic, food, sanitary, cosmetic and pharmaceutical (2,3).References:
- Progress in the Chemistry of Fats and other Lipids. Metabolism of plant terpenoids. George R. Waller. Volume 10, 1970, Pages 153-212. https://www.sciencedirect.com/science/article/pii/0079683270900066
- Biological effects of essential oils – A review. F. Bakkali, S. Averbeck, D. Averbeck and M. Idaomar. Food and Chemical Toxicology. Volume 46, Issue 2, February 2008, Pages 446-475. https://doi.org/10.1016/j.fct.2007.09.106
- Linalool bioactive properties and potential applicability in drug delivery systems. Irina Pereira, Patrícia Severino, Ana C. Santos, Amélia M. Silva and Eliana B. Souto. Colloids and Surfaces B: Biointerfaces. Volume 171, 1 November 2018, Pages 566-578. https://doi.org/10.1016/j.colsurfb.2018.08.001
3-carboxy-4-methyl-5-propyl-2-furan propanoic acid or CMPF is a heterocyclic fatty acid, and a major metabolite of furan fatty acids. Furan fatty acids naturally occur in algae, plants, organic dairy products, fish and some bacteria(1,2,3,4). Increased levels of CMPF have been found in patients with diabetes type 2 and recent studies have shown some evidence indicating that CMPF may be a biomarker for diabetes T2 progression(1,3) and renal impairment(1). Humans acquire furan fatty acids from the consumption of a wide range of foods such as vegetables, fruits, seed oil, dairy products, fish and fish oil(1,2,4). These compounds are scavengers of free radicals and can protect polyunsaturated fatty acids from oxidation(1,4)and at the same time they can be mainly metabolised to CMPF(1) raising the debate whether furan fatty acids intake could be harmful or beneficial for health.References:
- Furan fatty acids – Beneficial or harmful to health? Long Xu, Andrew J. Sinclair, Muniba Faiza, Daoming Li, Xianlin Han, Huiyong Yin and Yonghua Wang. Progress in Lipid Research. Volume 68, 2017, Pages 119-137. https://doi.org/10.1016/j.plipres.2017.10.002
- High Concentrations of Furan Fatty Acids in Organic Butter Samples from the German Market. Christine Wendlinger and Walter Vetter. J. Agric. Food Chem., 2014, 62 (34), pp 8740–8744. DOI: 10.1021/jf502975b. https://pubs.acs.org/doi/abs/10.1021/jf502975b
- Detailed Study of Furan Fatty Acids in Total Lipids and the Cholesteryl Ester Fraction of Fish Liver. Christine Wendlinger, Simon Hammann and Walter Vetter. Food Analytical Methods. Volume 9, Issue 2, 2016, pp 459–468. https://link.springer.com/article/10.1007%2Fs12161-015-0211-x
- Synthesis and scavenging role of furan fatty acids. Rachelle A. S. Lemke, Amelia C. Peterson, Eva C. Ziegelhoffer, Michael S. Westphall, Henrik Tjellström, Joshua J. Coon, and Timothy J. Donohue. Proceedings of the National Academy of Sciences of the United States of America. Volume 111, Issue 33, 2014, pp. 3450-57. https://doi.org/10.1073/pnas.1405520111
2-Arachidonoylglycerol also known as 2-AG is a monoacylglycerol neurotransmitter that binds to cannabinoid receptors located in the mammalian central nervous system (including the brain) and peripheral nervous system 1. 2-AG and anandamide (LMFA08040001) are involved in regulating a variety of physiological and cognitive processes as part of the endocannabinoid system (ECS) which includes fertility, pregnancy, appetite, pain-sensation, mood (depression and memory) and in mediating the pharmacological effects of cannabis (1,2,3). In contrast, ECS is up-regulated in numerous pathophysiological states such as inflammatory, neurodegenerative, gastrointestinal, metabolic and cardiovascular diseases, pain, and cancer therefore enhancement of endogenous endocannabinoid tone by inhibition of endocannabinoid degradation represents a promising therapeutic approach for the treatment of many diseases (4).References:
- Bruce A. Watkins. Endocannabinoids, exercise, pain, and a path to health with aging. Molecular Aspects of Medicine. Volume 64, December 2018, pp. 68-78. https://www.sciencedirect.com/science/article/pii/S0098299718300359
- Inés Ibarra-Lecue, Fuencisla Pilar-Cuéllar, Carolina Muguruza, Eva Florensa-Zanuy, Álvaro Díaz, Leyre Urigüen, Elena Castro, Angel Pazos and Luis F. Callado. The endocannabinoid system in mental disorders: Evidence from human brain studies. Biochemical Pharmacology. Volume 157, 2018, pp. 97-107. https://www.sciencedirect.com/science/article/pii/S0006295218302776
- D. Pascual, E. M. Sánchez-Robles, M. M. García and C. Goicochea. Chronic pain and cannabinoids. Great expectations or a christmas carol. Biochemical Pharmacology, Volume 157, 2018, pp.33-42. https://www.sciencedirect.com/science/article/pii/S0006295218303010
- Marek Toczek and Barbara Malinowsk. Enhanced endocannabinoid tone as a potential target of pharmacotherapy. Life Sciences. Volume 204, 1 July 2018, pp. 20-45. https://www.sciencedirect.com/science/article/pii/S0024320518302352
γ-Tocopherol ((2R)-2,7,8-trimethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-chromen-6-ol) is one of the eight types of vitamin E and abundantly found in seeds (almond, pumpkin, walnuts, pecans, etc.). It has antioxidant properties due to its capability to trap nitrogen-based free radicals or reactive nitrogen oxide species (RNOS).
Epigallocatechin 3,3',-di-O-gallate, also known as EGCG is a polyketide lipid that belongs to the main class of flavonoids known as catechins which can be mainly derived or extracted naturally from green and black tea(1-3). However, as a flavonoid, this compound can be found in many other food products such cocoa, onions, plums, pecan and hazelnuts but in trace amounts(2). The widespread consumption of green tea around the world has been promoted due to its positive health effects attributed to the antioxidant and anti-inflammatory properties of compounds such EGCG contained within(4). However, other studies have highlighted that EGCG might protect from oxidative damages and could reduce cancer risk or other diseases caused by free radicals(3,5).
- Medicinal Plants: Their Use in Anticancer Treatment. M. Greenwell and P.K.S.M. Rahman. Int Journal of Pharmacological Science Research. Volume 6. Issue 10, 2005, pp. 4103–4112. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650206/
- Green tea polyphenol epigallocatechin-3-gallate differentially modulates oxidative stress in PC12 cell compartments. Raza H and John A. Toxicology and Applied Pharmacology. Volume 15. Issue 207(3), pp. 212-20. https://www.ncbi.nlm.nih.gov/pubmed/16129114
- Effect of increased tea consumption on oxidative DNA damage among smokers: a randomized controlled study. Hakim IA, Harris RB, Brown S, Chow HH, Wiseman S, Agarwal S, Talbot W. Journal of Nutrition. Volume 133. Issue 10, 2003, pp. 3303S–3309S. https://www.ncbi.nlm.nih.gov/pubmed/14519830
Oleic acid (Systematic Name:9Z-octadecenoic acid) is a monounaturated fatty acid whose name derives from the latin word 'oleum', which means oil. It is the most common fatty acid in nature, typically occurring in esterified form in glycerolipids and phospholipids. The biosynthesis of oleic acid involves the action of the enzyme stearoyl-CoA 9-desaturase acting on the saturated precursor stearoyl-CoA.
Jasmonic acid (systematic name: (1R,2R)-3-oxo-2-(pent-2Z-enyl)-cyclopentaneacetic acid) is an truncated octadecanoid present in several plants including jasmine. Jasmonic acids are a class of plant hormones which are involved in development, abiotic stress responses and plant-microbes interactions in defence and symbiosis. Derivates such as methyl-jasmonate are volatile and participate in long range signalling between plants. Jasmonic acid is synthesized from alpha linolenic acid which is first oxygenated by Lipoxygenase (13-LOX) and subsequently modified by beta oxidation to yield a C12 cyclic product.
Sphingomyelins, such as SM(d18:1/16:0) (systematic name: N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine) are a class of sphingolipids composed of the long-chain sphingosine base attached to a fatty acid via an N-acyl linkage and a phosphocholine head group. In humans, sphingomyelins represent ~85% of all sphingolipids, and typically make up 10-20 mol % of plasma membrane lipids. They resemble phosphatidylcholines in their general properties and three-dimensional structure, and in having no net charge on their head groups.
Deoxycholic acid (systematic name:3alpha,12alpha-Dihydroxy-5beta-cholan-24-oic acid), a C24 bile acid, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. The two primary bile acids secreted by the liver are cholic acid and chenodeoxycholic acid. Bacteria metabolize chenodeoxycholic acid into the secondary bile acid lithocholic acid, and they metabolize cholic acid into deoxycholic acid. Sodium deoxycholate, the sodium salt of deoxycholic acid, is often used as a biological detergent to lyse cells and solubilise cellular and membrane components.
Deoxycholic acid (systematic name:3alpha,12alpha-Dihydroxy-5beta-cholan-24-oic acid), a C24 bile acid, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. The two primary bile acids secreted by the liver are cholic acid and chenodeoxycholic acid. Bacteria metabolize chenodeoxycholic acid into the secondary bile acid lithocholic acid, and they metabolize cholic acid into deoxycholic acid. Sodium deoxycholate, the sodium salt of deoxycholic acid, is often used as a biological detergent to lyse cells and solubilise cellular and membrane components.
Anandamide (Systematic Name: N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine), also known as N-arachidonoylethanolamine or AEA, is a fatty acid neurotransmitter derived from the non-oxidative metabolism of arachidonic acid an essential w-6 polyunsaturated fatty acid. It is synthesized from N-arachidonoyl phosphatidylethanolamine (NAPE) by multiple pathways and is degraded primarily by the fatty acid amide hydrolase (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid.
Palmitelaidic acid (systematic name: 9E-hexadecenoic acid) is a trans fatty acid (the trans isomer of palmitoleic acid). Trans fatty acids are known to cause changes in plasma lipids and lipoprotein phenotypes, but the mechanisms involved are unknown. The major dietary sources of trans fatty acids are partly hydrogenated vegetable oils, mainly elaidic acid (9E-octadecenoic acid). Additional sources are animal and dairy fats (palmitelaidic acid and trans-vaccenic acid (11E-octadecenoic acid)) and partly hydrogenated fish oils. Palmitelaidic acid has been reported as the predominant trans-16:1 isomer in cheeses made with goat and sheep milk.
ELV-N34, (Systematic Name:(16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydroxydotetratriaconta-16,19,23,25, 27,31-hexaenoic acid) represents a novel class of lipid mediators biosynthesized in human retinal pigment epithelial (RPE) cells that are oxygenated derivatives of very long-chain polyunsaturated fatty acids (VLC-PUFAs,n-3). These mediators have been named elovanoids (ELV) and are necessary for neuroprotective signaling for photoreceptor cell integrity. Photoreceptor cells express the elongase enzyme ELOVL4 which catalyzes the biosynthesis of elovanoids from 22:6 fatty acids derived from DHA or EPA.
Coniferonic acid (Systematic name:5Z,9Z,12Z,15Z-octadecatetraenoic acid) is a C18 Delta(5)-unsaturated bis-methylene-interrupted fatty acid commonly found in pine seed oil. It is assumed to be synthesized from alpha-linolenic acid (ALA; 18:3Delta(9,12,15)) by Delta(5)-desaturation. A unicellular green microalga Chlamydomonas reinhardtii also accumulates this fatty acid in a betaine lipid.
Ursodeoxycholic acid or ursodiol (sytematic name: 3alpha,7beta-dihydroxy-5beta-cholan-24-oic acid) is a 24-carbon secondary bile acid, which are metabolic byproducts of intestinal bacteria. Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which the intestine absorbs cholesterol molecules while breaking up micelles containing cholesterol. Because of this property, ursodeoxycholic acid is used to treat (cholesterol) gallstones non-surgically. Ursodeoxycholic acid has also been shown experimentally to suppress immune response such as immune cell phagocytosis.
2-oleoyl-glycerol (Systematic Name:2-(9Z-octadecenoyl)-sn-glycerol) is a monoacylglycerol that is found in biological tissues. Monoacylglycerols or monoglycerides are a class of glycerolipids which are composed of a molecule of glycerol linked to a fatty acid via an ester bond. They are typically present at low levels in cell extracts but are intermediates in the degradation of triacylglycerols and diacylglycerols (lipolysis). 2-oleoyl-glycerol was found to be an endogenous ligand to the G protein-coupled receptor GPR119 and has been shown to increase glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels following administration to the small intestine.
The eicosanoid Leukotriene C4 (LTC4) is the parent cysteinyl leukotriene produced by the LTC4 synthase (glutathione S-transferase II) catalyzed conjugation of glutathione to LTA4. LTC4 is produced by neutrophils, macrophages, mast cells, and by transcellular metabolism in platelets. It is one of the constituents of slow-reacting substance of anaphylaxis (SRS-A) and exhibits potent smooth muscle contracting activity. LTC4-induced bronchoconstriction and enhanced vascular permeability contribute to the pathogenesis of asthma and acute allergic hypersensitivity.
Diplotene (systematic name:Hop-22(29)-ene) is a commonly occurring member of the Hopanoid class of Prenol lipids. Hopanoids are natural pentacyclic compounds based on the chemical structure of hopane and have been found to be present in nature in vast amounts as components of bacteria and other primitive organisms. A range of hopanoids are found in petroleum reservoirs, where they are used as biological markers and they have also been found some terrestrial ferns. Hopanoids are one of the most abundant natural products on earth and are present in the organic matter of all sediments, independent of their age, origin or nature and are useful molecular fossil biomarkers in reconstruction of early evolution and geology.
Alpha-linolenic acid or ALA (systematic Name: 9Z,12Z,15Z-octadecatrienoic acid) is an unsaturated fatty acid found primarily in seeds and vegetable oils. ALA is categorized as an omega-3 fatty acid, and is an isomer of gamma-linolenic acid, which is a polyunsaturated omega-6 fatty acid. It is an essential fatty acid because it is necessary for health and cannot be produced within the human body. ALA can only be obtained by humans through their diets because the absence of the required 12- and 15-desaturase enzymes makes de novo synthesis from stearic acid or oleic acid impossible.
Gamma-linolenic acid or GLA (systematic Name: 6Z,9Z,12Z-octadecatrienoic acid) is an unsaturated fatty acid found primarily in vegetable oils. GLA is categorized as an omega-6 fatty acid, and is an isomer of alpha-linolenic acid, which is a polyunsaturated omega-3 fatty acid, found in rapeseed canola oil, soy beans, walnuts, flax seed (linseed oil) and hemp seed. The human body produces GLA from linoleic acid (LA). This reaction is catalyzed by the enzyme delta6-desaturase (D6D). LA is consumed sufficiently in most diets, from such abundant sources as cooking oils and meats.
Sulfoquinovosyl diacylglycerols, (SQDG), are a class of sulfur-containing but phosphorus-free lipids (sulfolipids) found in many photosynthetic organisms. SQDG has been found in all photosynthetic plants, algae, cyanobacteria, purple sulfur and non-sulfur bacteria and is localised in the thylakoid membranes, where it appears to be important for membrane structure and function and for optimal activity of photosynthetic protein complexes. It has been estimated to be one of the most abundant organosulfur species in the biosphere and thus plays a major role in the global biogeochemical sulfur cycle. A structure examples is SQDG(16:0/16:0) (1,2-dihexadecanoyl-3-(6'-sulfo-a-D-quinovosyl)-sn-glycerol).
15R-hydroxy-12S,14R-dioxolane-EET (15R-hydroxy-12S,14R-dioxolane-5Z,8Z,10E-eicosatrienoic acid) is an eicosanoid containing a 1,2-dioxolane (cyclic peroxide) group. Dioxolanes of this type have been generated from enantiomers of 14,15-EET by two mammalian LOX enzymes, 15-LOX-1 and platelet-type 12-LOX. This type of transformation could occur naturally with the co-occurrence of LOX and cytochrome P450 or peroxygenase enzymes.
Retinal (all-trans-retinal) is a polyene isoprenoid chromophore, bound to proteins called opsins, and is the chemical basis of animal vision. Retinal exists in two forms, a cis and a trans isomer. On illumination with white light, the visual pigment, cis-retinal is converted to trans-retinal. This isomer must be transformed back into the cis form by retinal isomerase before it combines again with opsin (dark phase). Both isomers can be reduced to retinol (vitamin A) by a NADH-dependent alcohol dehydrogenase.
Hyodeoxycholic acid (HDCA)
Hyodeoxycholic acid (HDCA) or 3alpha,6alpha-Dihydroxy-5beta-cholan-24-oic acid is a C-24 secondary bile acid, one of the metabolic byproducts of intestinal bacteria. HDCA is present in mammalian species in different proportions and is the main acid constituent of hog bile. Hyodeoxycholic acid undergoes glucuronidation in human liver and kidneys via the enzyme UDP-glucuronosyltransferase.
Myristic acid, or tetradecanoic acid, is a common saturated fatty acid named after the nutmeg Myristica fragrans. Myristic acid is also found in palm kernel oil, coconut oil, butter fat and is a minor component of many other animal fats. It is used to synthesize flavor and as an ingredient in soaps and cosmetics. Myristoylation is a co-translational or post-translational modification where a myristoyl group, derived from myristic acid, is covalently attached by an amide bond to the alpha-amino group of an N-terminal glycine residue. Myristoylation plays an essential role in membrane targeting, protein-protein interactions and functions widely in a variety of signal transduction pathways.
Phosphatidylinositols (for example PI(16:0/18:1)) consist of a class of glycerophospholipids containing a myo-inositol group headgroup. Typically phosphatidylinositols form a minor component on the cytosolic side of eukaryotic cell membranes. Biosynthesis of phosphatidylinositol from CDP-diacylglycerol and myo-inositol is catalyzed by phosphatidylinositol synthase in eukaryotes. Phosphatidylinositols can be phosphorylated by a number of different kinases to form phosphatidylinositol phosphates (PIP), phosphatidylinositol bisphosphates (PIP2) and phosphatidylinositol trisphosphates (PIP3). These molecules play important roles in lipid signaling, cell signaling and membrane trafficking.
Stigmasterol (stigmasta-5,22E-dien-3beta-ol) is an unsaturated phytosterol (plant sterol) occurring in the plant fats or oils of soybean, rape seed, and in a number of medicinal herbs. It differs structurally from cholesterol due to the presence of a side-chain double bond and ethyl group. Stigmasterol is also found in various vegetables, legumes, nuts, seeds, and unpasteurized milk. Phytosterols normally are broken down in the bile.
C16-Sphingomyelin or SM(d18:1/16:0) ( systematic name: N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine) is a commonly occurring member of the sphingomyelin class of sphingolipids. Sphingomyelins are present in the plasma membranes of animal cells and are especially prominent in myelin, a membranous sheath that surrounds and insulates the axons of some neurons. Sphingomyelins contain a phosphocholine polar head group attached to a ceramide backbone and resemble phosphatidylcholines in their general properties and three-dimensional structure.
Leukotriene B4 (5S,12R-dihydroxy-6Z,8E,10E,14Z-eicosatetraenoic acid) is a pro-inflammatory eicosanoid mediator synthesised in myeloid cells from arachidonic acid. Synthesis is catalysed by 5-lipoxygenase and leukotriene A4 hydrolase and is increased by inflammatory mediators including endotoxin, complement fragments, tumor necrosis factor and interleukins. Leukotriene B4 is able to induce the adhesion and activation of leukocytes on the endothelium, allowing them to bind to and cross it into the tissue. In neutrophils, it is also a potent chemoattractant, and is able to induce the formation of reactive oxygen species and the release of lysosomal enzymes by these cells.
Chenodeoxycholic acid (3alpha,7alpha-dihydroxy-5ß-cholan-24-oic acid) is a C24 bile acid and one of the main bile acids produced by the liver. Chenodeoxycholic acid is synthesized in the liver from cholesterol and can be conjugated in the liver with taurine or glycine, forming taurochenodeoxycholic acid or glycochenodeoxycholic acid. Chenodeoxycholic acid is the most potent natural bile acid for stimulating the nuclear bile acid receptor, farnesoid X receptor. The transcription of many genes is activated by FXR.
Ceramides, such as Cer(d18:1/16:0) (systematic name: N-(hexadecanoyl)-sphing-4-enine) are a class of sphingolipids composed of the long-chain base sphingosine attached to a fatty acid via an N-acyl linkage. Ceramides are found in high concentrations within the cell membrane of cells. De novo synthesis of ceramide occurs in the endoplasmic reticulum. Ceramide is subsequently transported to the Golgi apparatus by either vesicular trafficking or the ceramide transfer protein CERT. Once in the Golgi apparatus, ceramide can be further metabolized to other sphingolipids, such as sphingomyelin (a key component of cell membranes) and the complex glycosphingolipids.
Cyanidin (2-(3,4-Dihydroxyphenyl) chromenylium-3,5,7-triol) is a polyketide metabolite belonging to the anthocyanidin subclass of flavonoids. It is a pigment found in many red berries including grapes, bilberry, blackberry and blueberry. Cyanidin, like other anthocyanidins, has putative antioxidant and radical-scavenging effects which may protect cells from oxidative damage and reduce risk of cardiovascular diseases and cancer.
Oleanolic acid ((3beta-hydroxyolean-12-en-28-oic acid)) is a naturally occurring pentacyclic triterpenoid related to betulinic acid. It is widely distributed in food and plants where it exists as a free acid or as an aglycone of triterpenoid saponins. Oleanolic acid is relatively non-toxic, hepatoprotective, and exhibits antitumor and antiviral properties.
Palmitic acid (LMFA01010001), or hexadecanoic acid, is the most common saturated fatty acid found in animals, plants and microorganisms. As its name indicates, it is a major component of the oil from palm trees (palm oil), but can also be found in meats, cheeses, butter, and dairy products. Palmitic acid is the first fatty acid produced during fatty acid synthesis and the precursor to longer chain fatty acids. Palmitic acid is used to produce soaps and cosmetics. These applications utilize sodium palmitate, which is commonly obtained by saponification of palm oil.
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, sperm, testicles and retina. It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk or fish oil. It's systematic name is 4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid. DHA is the most abundant omega-3 fatty acid in the brain and retina. DHA comprises 40% of the polyunsaturated fatty acids (PUFAs) in the brain and 60% of the PUFAs in the retina. Fifty percent of the weight of a neuron's plasma membrane is composed of DHA.
Sphingosine-1-phosphate (S1P) is an signaling sphingolipid and is composed of a C18 sphingoid base with a phosphate group at the C1 position. Phosphorylation of sphingosine to S1P is catalyzed by sphingosine kinase, an enzyme ubiquitously found in the cytosol and endoplasmatic reticulum of various types of cells. Although S1P is of importance in the entire human body, it is a major regulator of vascular and immune systems. In the vascular system, S1P regulates angioge nesis, vascular stability, and permeability. In the immune system, it is now recognized as a major regulator of trafficking of T- and B-cells.
Resolvin D2 (7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid) is a member of class of eicosanoids and docosanoids known as resolvins. Resolvins are compounds that are made by the human body from the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). They are produced by the COX-2 pathway especially in the presence of aspirin. Experimental evidence indicates that resolvins reduce cellular inflammation by inhibiting the production and transportation of inflammatory cells and chemicals to the sites of inflammation.
Taurocholic acid ,(N-(3alpha,73alpha,123alpha-trihydroxy-5beta-cholan-24-oyl)-taurine), known also as cholyltaurine, is a bile acid conjugate involved in the emulsification of fats. It occurs as a sodium salt in the bile of mammals. It is a conjugate of cholic acid with taurine.
12-oxo Phytodienoic acid (OPDA) or 12-oxo-PDA LMFA02010001 is an octadecanoid and a biologically active, immediate precursor of 7-epi jasmonic acid. In addition to its link with jasmonic acid activity, OPDA appears to play an independent role in mediating resistance to pathogens and pests.
Geranial, or 3,7-dimethyl-2E,6-octadienal is a monoterpenoid with the molecular formula C10H16O. The two compounds are double bond isomers. The 2E-isomer is also called citral A. The 2Z-isomer is known as neral or citral B. Geranial is present in the oils of several plants, including limes, lemons and oranges and has a strong lemon odor. It also has strong antimicrobial qualities and pheromonal effects in insects.
Mayolene-16 or 11R-hexadecanoyloxyoctadeca-9Z,12Z,15Z-trienoic acid is a member of a class of fatty esters (mayolenes) found in the larvae of the European cabbage butterfly, Pieris rapae. They are composed of esters between straight-chain fatty acids and 11-hydroxy alpha-linolenic acid. The mayolenes have been shown to act as potent chemical deterrents to larval predators such as ants.
Myristoleic acid, or 9Z-tetradecenoic acid, is an omega-5 fatty acid. It is biosynthesized from myristic acid by the enzyme delta-9 desaturase, but it is uncommon in nature. One of the major sources of this fatty acid is the seed oil from plants of the family Myristicaceae, comprising up to 30 per cent of the oil in some species.
Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the receptor PTGDR, as well as CRTH2. It is a major prostaglandin produced by mast cells and recruits Th2 cells, eosinophils, and basophils. In mammalian organs, large amounts of PGD2 are found only in the brain and in mast cells. It is critical to development of allergic diseases such as asthma. Cellular synthesis occurs through the arachidonic acid cascade with the final conversion from PGH2 performed by PGD2 synthase (PTGDS).
Lauric acid, or dodecanoic acid, is a saturated fatty acid with a 12-carbon atom chain. Lauric acid, as a component of triglycerides, comprises about half of the fatty acid content in coconut oil, laurel oil, and palm kernel oil. It is also found in human breast milk (6.2% of total fat), cow's milk and goat's milk. Industrially, it is mainly used for the production of soaps and cosmetics.
Lithocholic acid, or 3alpha-hydroxy-5beta-cholan-24-oic acid is a monohydroxy secondary bile acid that acts as a detergent to solubilize fats for absorption. Bacterial action in the colon produces lithocholic acid from chenodeoxycholic acid by reduction of the C7 hydroxyl group in the B ring. Lithocholic acid can activate the vitamin D receptor without raising calcium levels as much as vitamin D itself.
Aldosterone (LMST02030026) is a steroid hormone of the mineralocorticoid family synthesized from cholesterol in the adrenal gland. It plays a central role in the regulation of blood pressure, mainly by acting on the distal tubules and collecting ducts of the nephron, increasing reabsorption of ions and water. When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and renal disease. Aldosterone is part of the renin-angiotensin system and tends to promote Na+ and water retention, and lower plasma K+ concentration.
Jasmonic Acid (LMFA02020001), is a C12 fatty acid which is is biosynthesized from linolenic acid by the octadecanoid pathway. It is a plant growth regulator involved in the signaling mechanisms for a variety of conditions including plant defense, wound healing, tuberization, fruit ripening, and senescence Jasmonic acid is also converted to a variety of derivatives including esters such as methyl jasmonate and may also be conjugated to amino acids.
Chenodeoxycholic Acid (LMST04010032), along with cholic acid, is one of two primary bile acids found in humans. Chenodeoxycholic Acid is synthesized in the liver from cholesterol. It is known to aid digestion and can be used to dissolve gallstones and in the treatment of cerebral cholesterosis.