Fatty Acids: Polyunsaturated with Other than
Methylene-Interrupted Double Bonds
Two types of unsaturated fatty acids are considered here - those with conjugated double bond systems, and those in which the double bonds are separated by two or more methylene groups. Related fatty acids from plant systems may have acetylenic bonds or oxygenated groups, and these are discussed separately. Similarly, the eicosanoids and hydroperoxides, which can also have conjugated double bond systems, are discussed in other documents. Mainstream polyunsaturated fatty acids with methylene-interrupted double bonds of course have their own web page.
1. Conjugated Fatty Acids Derived from Bacteria in Animal Tissues
Fatty acids with conjugated diene systems are found in tissues of ruminant animals, where they are formed as intermediates or by-products in the biohydrogenation of linoleic and linolenic acids by microorganisms in the rumen, and thence they make their way into meat and dairy products and eventually into human tissues. The main isomer, 9-cis,11-trans-octadecadienoic acid, amounts to about 1% of the fatty acids of milk fat, and it may be accompanied by a small proportion of positional and geometrical isomers, both with conjugated double bonds (6,8- to 12,14-18:2) or less often with two or more methylene groups between double bonds. An analogous fatty acid derived from α-linolenic acid, 9-cis,11-trans,15-cis-octadecatrienoic acid is usually detected at trace levels only in ruminant tissues. One consequence of the biohydrogenation process is that the levels of the precursor essential fatty acids in ruminant tissues are very low. In addition, conjugated fatty acids have been produced by microbial fermentation from a number of other polyunsaturated fatty acids experimentally, and their biological properties are under investigation.
A number of routes to the biosynthesis of the conjugated linoleate isomer have been suggested for various bacterial species, and for example a linoleate isomerase has been proposed for Butyrivibrio fibrisolvens. However, in Lactobacillus plantarum the process occurs in two steps: in the first, a linoleate 10-hydratase produces the intermediate 10-hydroxy-octadec-12-cis-enoic acid, before this is acted upon by an enolase to produce 9-cis,11-trans-octadecadienoic acid.
Although most of the conjugated fatty acids in animal tissues are probably obtained from the diet, some may be produced by linoleate isomerases in intestinal microorganisms, even in humans. There is considerable interest in conjugated linoleic acid ('CLA') at present because of reports that it has a number of beneficial medical properties, especially anti-cancer effects. Depending on the specific isomer, it is also claimed to have anti-atherosclerosis effects, to help the immune system and to affect energy metabolism, promoting protein deposition as opposed to fat. The material sold as a nutritional supplement is produced commercially by alkaline isomerization of linoleate-rich oils, and consists of equimolar amounts of 9c,11t- and 10t,12c-18:2, together with variable amounts of positional and geometrical isomers. This mixture does not necessarily have the same beneficial effects as the individual isomers. As described in our web pages on methylene-interrupted polyunsaturated fatty acids, the CLA isomers can undergo chain elongation and desaturation to eventually form analogues of arachidonic acid with a conjugated double bond system. Although the rate of this reaction is low, it is possible that the metabolites could have biological activity. Shorter-chain metabolites of CLA are found in tissues as a result of beta-oxidation. It is now recognized that conjugated linoleate reacts to produce nitro fatty acids in animal tissues with great facility and may be the primary endogenous substrate for fatty acid nitration in vitro and in vivo; nitro-CLA isomers have been detected in plasma and urine of healthy humans.
2. Conjugated Fatty Acids Produced in Animals
In relation to the above, some synthesis of conjugated fatty acids from specific dietary precursors occurs also within organs such as the liver, of animals. Thus, trans-7,cis-9-octadecadienoate is synthesised endogenously from trans-7-18:1 by means of a Δ9-desaturase in dairy cows. While 9c,11t-18:2 is produced similarly in human tissues by desaturation of trans-11-octadecenoate (vaccenic acid - also primarily of microbial origin) from the diet, rodent tissues, including lactating mammary gland, produce the 11t,13c isomer from the same precursor by means of the FADS3 desaturase, i.e. a unique methyl-end Δ13-desaturation in animals.
Fatty acid-like, all-trans-polyenes are the yellow pigment in budgerigar feathers, and unusually for an animal product they are produced by a polyketide synthase rather than a fatty acid synthase. In addition, the nematode Caenorhabditis elegans utilizes a polyketide synthase to produce a C18 fatty acid with 3/4 double bonds in conjugation and other functional groups linked to tetrapeptides (nemamides A and B). A short-chain conjugated fatty acid, 2-trans,4-trans-hexadienoic (sorbic) acid, is a characteristic component of triacylglycerols in the surface wax of aphids, where it is found exclusively in position sn-2.
3. Conjugated Fatty Acids from Plants
trans-10,trans-12-Octadecadienoic acid comprises about 10% of the seed oil of Chilopsis linearis and appears to be the only long-chain conjugated dienoic fatty acid from plant sources, although trans-2,cis-4-decadienoic acid is present in estolide linkage to an allenic hydroxy acid in Stillingia oil. Conjugated dienoic fatty acids in refined oils are mainly artefacts of processing.
In contrast, fatty acids with conjugated triene systems have been found in a large number of different plant species. Of these, 9-cis,11-trans,13-trans-octadecatrienoic (α-eleostearic) acid is the most widespread and best known, and tung oil is the main commercial source.
Other geometrical isomers of this fatty acid are found in seed oils, and these include 9-cis,11-trans,13-cis- and 9-trans,11-trans,13-cis-octadecatrienoic acids ('punicic' and 'catalpic' acids, respectively). The first is found in the seed oil from pomegranate and related species, and the second from Catalpa ovata. In addition, two 8,10,12-18:3 isomers are known, i.e. 8t,10t,12c-18:3 ('calendic' acid) from marigold seeds (Calendula officinalis), and 8c,10t,12c-18:3 from Jacaranda seeds.
Rhizobium bacteria interact with leguminous plants in a host-specific manner to form nitrogen-fixing root nodules, and an unusual C18 tetraenoic fatty acid with three double bonds in conjugation, trans-2,trans-4,trans-6,cis-11-octadecatetraenoic acid, is a key component of the signalling mechanism that initiates the process.
A conjugated tetraenoic acid, 9-cis,11-trans,13-trans,15-cis-octadecatetraenoic or 'α-parinaric' acid, is a major constituent of seed oils from Parinarium and Impatiens species. Further unusual fatty acids with four conjugated double bonds in addition to methylene-interrupted double bonds are produced by some marine algae (e.g. 4Z,7Z,9E,11E,13Z,16Z,19Z-docosaheptaenoic acid).
All conjugated tri- and tetraenoic acids isomerize readily to the all-trans or beta-forms, which are more stable thermodynamically, especially in the presence of alkali or on heating.
Calendic acid (8t,10t,12c-18:3) is synthesised in Calendula officinalis from linoleate (9c,12c-18:2) by an unusual Δ12-oleate desaturase (a FAD2 variant) that converts the cis-double bond in position 9 to a trans,trans-conjugated double bond system (8t,10t). As a result of a small change only in the position of the iron oxidant at the active centre of the enzyme relative to the substrate, the site of the initial hydrogen abstraction is at C-11 rather than C-12, as is more usual. Similarly, punicic acid is synthesised in plants from linoleate by a related desaturase that converts the cis-double bond in position 12 to a trans,cis-conjugated double bond system (11t,13c).
There is increasing interest in the potential health-giving properties of natural conjugated trienoic fatty acids for which studies in vitro and in vivo have demonstrated anti-inflammatory, anti-obesity, immuno-modulatory and anti-carcinogenic activities, as well as improvements to cardiovascular health.
4. Bis- and Polymethylene-Interrupted Unsaturated Fatty Acids from Marine Invertebrates
The primitive animals the sponges (family - Spongillidae) and some other marine invertebrates are known to contain a wide range of distinctive fatty acids, the demospongic acids, with bis-methylene-interrupted cis-double bonds, and ranging in chain-length from C16 to C34. These fatty acids have a cis,cis-dienoic system of two types, either with the double bonds in positions 5 and 9, or derived from 5,9-16:2 by chain-elongation. The second type is usually a relatively minor component of sponges, and was first reported from the cellular slime mould Dictyostelium discoideum.
Homologous fatty acids from 5,9-16:2 to 5,9-34:2, both odd and even-numbered, can be found in a single species of sponge. Similarly, 5,9-16:2, 7,11-18:2, 9,13-20:2 and so forth to 23,27-34:2, which are presumably formed by sequential chain-elongation of 5,9-16:2, have been found in one species. Related fatty acids occur with a methyl branch, often in the iso- or anteiso-position but also located more centrally (e.g. 22-methyl-5,9-28:2), and multi-branched (isoprenoid) demospongic fatty acids have been found in at least one fresh-water species. Similar fatty acids have been identified in many other marine invertebrates, including nudibranchs, limpets, sea anemones and gorgonians.
One trienoic fatty acid with in effect two bis-methylene-interrupted double bond systems, i.e. 5,9,13-20:3, has been found in sponges and other marine invertebrates, but most trienoic demospongic acids have one bis-methylene-interrupted double bond system with the third double bond in the n-7 or n-9 positions (e.g. 5,9,25-32:3). Some tetraenoic demospongic acids have two bis-methylene-interrupted double bond systems that are widely separated (e.g. 5,9,21,25-32:4). The most unusual is (all Z)-34S-methylhexatriaconta-5,9,12,15,18,21-hexaenoic acid, which is present in syriacin, a strange sulfated ceramide glycoside from the freshwater sponge Ephydatia syriaca.
Although the double bonds are normally of the cis configuration, a series of trans,trans-5,9-dienoic fatty acids was isolated from the sponge Plakortis halichondroides. Also, 5c,9c,19t-26:3 constituted 10% of the fatty acids from a fresh-water sponge, and related fatty acids have been found in the brittle star fish.
More than a hundred different fatty acids can be found in a single species of sponge. Although many of these are derived from the microflora and fauna that make up the food chain, the demospongic acids are certainly synthesised de novo by sponges. Thus, in the sponge Microciona prolifera, it has been demonstrated that 16:0 is elongated to the 26:0 fatty acid, which is then desaturated by Δ5 and Δ9 desaturases to form 5-26:1 and 9-26:1, respectively. These are both further desaturated to 5,9-26:2 by the same enzymes, i.e. unlike other animal systems, a double bond can be inserted before or after an existing double bond. Similarly, 5,9,19-26:3 is formed by elongation of 9-16:1 to 19-26:1, followed by desaturation in positions 5 and 9.
Dienoic fatty acids in which more than two methylene groups separate the double bonds are found in a wide range of marine invertebrates, but especially in molluscs and cephalopods. The most common of these are 5,11- and 5,13-20:2, and 7,13- and 7,15-22:2. 6,11-18:2 and 6,11-20:2 Fatty acids have been found in a marine sponge, while invertebrates from deep-sea hydrothermal vent ecosystems contain a number of unusual non-methylene-interrupted polyenes, including 5,13,16-20:3, 5,14,17-20:3 and 5,13,16,19-20:4. In bivalves, 7,13-22:2 and 7,15-22:2 are synthesised de novo by chain elongation, followed by Δ5 desaturation and further elongation of 9-18:1 and 9-16:1, respectively. The increasing availability of genetic information has enabled identification and characterization of both elongases and desaturases from such organisms. As anti-cancer activities have been reported, the pharmacological properties of some of these fatty acids are under investigation .
5. Bis- and Polymethylene-Interrupted Unsaturated Fatty Acids from Plants
Δ5-Unsaturated polymethylene-interrupted fatty acids with cis-double bonds only occur in appreciable amounts in seeds, leaves and other tissues of the relatively primitive plants, the gymnosperms (conifers). Of these, the best known is probably 5-cis,9-cis,12-cis-octadecatrienoic ('pinolenic') acid, which is widespread in species of pines. It is believed to have useful nutritional properties in that it has been shown to reduce plasma triacylglycerol and VLDL levels in rats.
A number of different fatty acids have been identified, some of which appear to be characteristic of specific families of gymnosperms. They include 5,11-18:2, 5,11-20:2, 5,9,12,15-18:4 (coniferonic), 5,11,14-20:3 (sciadonic), and 5,11,14,17-20:4 (juniperonic). Related branched-chain fatty acids, anteiso-methyl-5,9-18:2 and anteiso-methyl-5,9,12-18:3 acids have been found in pine wood extracts. In addition, 7,11-20:2 and 7,11,14-20:3 occur in some species, and they are presumably derived from chain elongation of the Δ5-C18 precursors. All of these have been given trivial names (the more common are listed), although they are only likely to be of interest to specialists. Incidentally, sciadonic acid has been detected in vivo in hormone positive breast cancer tissue, where it presumably results from a defect in arachidonic acid synthesis.
5-cis,13-cis-Docosadienoic acid (16% of the total fatty acids) occurs in the seed oil of a plant from a quite different family Limnanthes alba (meadowfoam). Trace levels of dienoic fatty acids with cis-double bonds in positions 5 and 9 have been found in a few other plant species, while 9,15-octadecadienoate occurs in mango pulp. In addition, an analogue of pinolenic acid with a trans double bond in position 5 (5t,9c,12c-18:3) is the main fatty acid constituent of the seed oil of Aquilegia vulgaris (columbine). A positional isomer of this, i.e. 3-trans,9-cis,12-cis-octadecatrienoate (accompanied sometimes by 3t,9c-18:2 and 3t,9c,12c,15c-18:4), is a common constituent of seed oils from the Compositae, and the all-cis isomer has also been described.
Pinolenic acid or 5,9,12-18:3 is synthesised in gymnosperms by the action of a Δ5 desaturase on linoleate, and presumably the other unusual acids in such plants are synthesised in the same way from appropriate precursors. For example, two distinctive front-end desaturases with Δ5 desaturase activity have been characterized from developing seeds of Anemone leveillei. Of these, one has a broad specificity for fatty acid substrates, while the other is specific for C20 fatty acids and especially for the biosynthesis of 5,11,14-20:3. There are reported to be health benefits when such fatty acids are included in animal diets.
6. Protozoa and Other Lower Organisms
The opportunistic protozoan pathogen Acanthamoeba castellanii contains 4,21,24-triacontatrienoic acid (not 5,21,14-30:3 as originally reported) as components of phosphatidylethanolamine and phosphatidylserine. Slime moulds contain fatty acids with bis- and poly-methylene-interrupted double bond systems in the 5,9- and 5,11-positions especially.
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|Credits/disclaimer||Updated: April 29th, 2021||Author: William W. Christie|