Each month we highlight a lipid of scientific interest. The LIPID MAPS Lipid of the Month Archive lists lipids highlighted from 2015 - present.
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:
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:
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:
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).
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.
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) 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.