Conjugated and Multimethylene-Interrupted Polyenoic

Two types of 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 will be considered elsewhere. Similarly, the eicosanoids and hydroperoxides, which can also have conjugated double bond systems, are discussed in other documents.

 

Conjugated Fatty Acids from Animal Tissues

Fatty acids with conjugated diene systems are found in tissues of ruminant animals, and thence in meat and dairy products, where it is formed as an intermediate or by-product in the biohydrogenation of linoleic acid by microorganisms in the rumen. 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 (6,8- to 12,14-18:2).

Structural formula of 9-cis,11-trans-octadecadienoic acid

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.

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. 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 (see our web-pages on CLA). The material sold as a nutritional supplement is produced 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. The CLA isomers can undergo chain elongation and desaturation as described in our web pages on polyunsaturated fatty acids, eventually to 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.

Although most of the conjugated fatty acids in animal tissues are probably derived from rumen micro-organisms via meat and dairy products, there is a possibility that some may be produced by intestinal microorganisms, even in humans. Some synthesis within the organs such as the liver of animals appears to occur also. 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) from the diet.

A short-chain conjugated fatty acid, 2-trans,4-trans-hexadienoic (sorbic) acid, is a characteristic component of aphid triacylglycerols, where it is found exclusively in position sn-2.

 

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. Tung oil is the main commercial source.

Formula of alpha-eleostearic acid

Other geometrical isomers of this fatty acid are found in seed oils, and 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 latter from Catalpa ovata. 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.

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 FAD 2 variant) that converts the cis-double bond in position 9 to a trans,trans-conjugated double bond system (8t,10t). It appears that the site of the initial hydrogen abstraction is at C-11 rather than C-12 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.

Biosynthesis of calendic acid

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 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.

 

Bis- and Polymethylene-Interrupted Unsaturated Fatty Acids from Animal Tissues

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 have a cis,cis-dienoic system, either with the double bonds in positions 5 and 9, or derived from a 5,9-16:2 fatty acid by chain elongation. The latter is usually a relatively minor component of sponges, and was first reported from the cellular slime mould Dictyostelium discoideum.

Formula of 5,9-hexadecadienoic acid

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. In addition, 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 freshwater 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 freshwater sponge, and related fatty acids have been found in the brittle starfish.

More than a hundred different fatty acids can be found in a single species of sponge. Most are derived from the microflora and fauna that make up the food chain, but 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.

Biosynthesis of 5,9-unsaturated fatty acids in sponges

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. The most common of these are 5,11- and 5,13-20:2, and 7,13- and 7,15-22:2. Many of the latter occur in slime moulds also. 6,11-18:2 and 6,11-20:2 Fatty acids have been found in a marine sponge. 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. 7,13-22:2 and 7,15-22:2. They are synthesised de novo in bivalves by chain elongation, followed by Δ5 desaturation of 9-18:1 and 9-16:1, respectively.

 

Bis- and Polymethylene-Interrupted Unsaturated Fatty Acids from Plants

Δ5-Unsaturated polymethylene-interrupted fatty acids, with cis-double bonds only, are found 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.

Formula of pinolenic acid

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, 5,11,14-20:3, and 5,11,14,17-20:4. 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.

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, is a common constituent of seed oils from the Compositae, and the all-cis isomer has also been described.

5,9,12-18:3 is synthesised in gymnosperms by the reaction of a Δ5 desaturase on linoleate, and presumably the other unusual acids in such plants are synthesised in the same way from appropriate precursors.

 

Recommended Reading

  • Barnathan, G. Non-methylene-interrupted fatty acids from marine invertebrates: Occurrence, characterization and biological properties. Biochimie, 91, 671-678 (2009) (DOI: 10.1016/j.biochi.2009.03.020).
  • Dembitsky, V.M., Rezanka, T. and Srebnik, M. Lipid compounds of freshwater sponges: family Spongillidae class Demospongiae. Chem. Phys. Lipids, 123, 117-155 (2003) (DOI: 10.1016/S0009-3084(03)00020-3).
  • Gunstone, F.D., Harwood, J.L. and and Dijkstra, A.J. (Editors). The Lipid Handbook (3nd Edition), Chapman & Hall, London) (2007).
  • Hennessy, A.A., Ross, R.P., Devery, R. and Stanton, C. The health promoting properties of the conjugated isomers of α-linolenic acid. Lipids, 46, 105-119 (2011) (DOI: 10.1007/s11745-010-3501-5).
  • Hopkins, C.Y. Fatty acids with conjugated unsaturation. In: Topics in Lipid Chemistry, Volume 3, pp. 37-87 (Edited by F.D. Gunstone, Paul Elek (Scientific Books), London) (1972).
  • Sébédio, J.-L., Christie, W.W. and Adlof, R. (Editors) Advances in Conjugated Linoleic Acid Research, Vol. 2. (AOCS Press, Champaign, IL) (2003). Volumes 1 and 3 of this series should also be consulted.
  • Wolff, R.L. and Christie, W.W. Structures, practical sources (gymnosperm seeds), gas-liquid chromatographic data (equivalent chain lengths), and mass spectrometric characteristics of all-cis 5-olefinic acids. Eur. J. Lipid Sci. Technol., 104, 234-244 (2002) (DOI: 10.1002/1438-9312(200204)104:43.0.CO;2-H).

Updated: March 7, 2011

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