FATTY ACIDS: STRAIGHT-CHAIN MONOENOIC
STRUCTURES, OCCURRENCE AND BIOCHEMISTRY
1. Structure and Nomenclature
Straight- or normal-chain (even-numbered), monoenoic components, i.e. with one double bond, make up a high proportion of the total fatty acids in most natural lipids. Normally the double bond is of the cis- or Z-configuration, although some fatty acids with trans- or E-double bonds are known.
The most abundant monoenoic fatty acids in animal and plant tissues are straight-chain compounds with 16 or 18 carbon atoms, but analogous fatty acids with 10 to 36 carbon atoms have been found in nature in esterified form. They are named systematically from the saturated hydrocarbon with the same number of carbon atoms, the final 'ane' being changed to 'enoic'. Thus, the fatty acid with 18 carbon atoms and the structural formula -
- is systematically named cis-9-octadecenoic acid, although it is more usual to see the trivial name oleic acid in the literature. In the shorthand nomenclature, it is designated '18:1' (or 9-18:1 or 9c-18:1). The position of the double bond can also be denoted in the form (n-x), where n is the chain-length of the fatty acid and x is the number of carbon atoms from the double bond to the terminal carbon atom of the molecule of the molecule, i.e. oleic acid is 18:1(n-9) (or often 18:1n-9, or in the early literature 18:1ω9). Although this contradicts the convention that the position of functional groups should be related to that of the carboxyl carbon, it is of great convenience to lipid biochemists. Animal and plant lipids frequently contain families of monoenoic fatty acids with similar terminal structures, but with different chain-lengths, that may arise from a common precursor either by chain-elongation or by beta-oxidation. The (n-x) nomenclature helps to point out such relationships.
A list of common monoenoic fatty acids together with their trivial names and shorthand designations is given in Table 1. However, trivial names are best avoided for all but the most common of these fatty acids (a comprehensive list of trivial names is available on the AOCS web site (see our Links page).
Table 1. The common monoenoic fatty acids
|Systematic name||Trivial name||Shorthand designation|
|cis-9-tetradecenoic||myristoleic||9-14:1 or 14:1(n-5)|
|cis-7-hexadecenoic||7-16:1 or 16:1(n-9)|
|cis-9-hexadecenoic||palmitoleic||9-16:1 or 16:1(n-7)|
|cis-6-octadecenoic||petroselinic||6-18:1 or 18:1(n-12)|
|cis-9-octadecenoic||oleic||9-18:1 or 18:1(n-9)|
|cis-11-octadecenoic||cis-vaccenic||11-18:1 or 18:1(n-7)|
|cis-11-eicosenoic||gondoic||11-20:1 or 20:1(n-9)|
|cis-13-docosenoic||erucic||13-22:1 or 22:1(n-9)|
|cis-15-tetracosenoic||nervonic||15-24:1 or 24:1(n-9)|
A cis-double bond in a fatty acid introduces a 30° bend in the alkyl chain, tending to result in looser packing in membranes or crystal structures. Very long-chain (20:1 upwards) cis-monoenoic fatty acids have relatively high melting points, but the more common C18 monoenes tend to be liquid at room temperature. Triacylglycerols (or oils and fats) containing high proportions of monoenoic fatty acids are usually liquid at ambient temperature. Analogous fatty acids with trans double bonds are normally higher melting.
Oleic acid (9c-18:1 or 18:1(n-9)) is by far the most abundant monoenoic fatty acid in plant and animal tissues, both in structural lipids and in depot fats. For example, it can comprise 30-40% of the total fatty acids in adipose fats of animals, and 20 to 80% of the seed oils of commerce. Olive oil contains up to 78% of oleic acid, and it is believed to have especially valuable nutritional properties as part of the Mediterranean diet. Indeed, it has a number of important biological properties discussed below, both in the free and esterified form. Oleic acid is the biosynthetic precursor of a family of fatty acids with the (n-9) terminal structure and with chain-lengths of 20 to 24 or more.
cis-Vaccenic acid (11c-18:1 or 18:1(n-7)) is a common monoenoic fatty acid of bacterial lipids, and it is usually present as a minor component of most plant and animal tissues. It is occasionally a more abundant constituent of plants, for example those containing appreciable amounts of its biosynthetic precursor, 9-16:1 (e.g. the fruit of sea buckthorn). Note that vaccenic acid per se is the trans isomer.
Petroselinic acid (6c-18:1) occurs up to a level of 50% or more in seed oils of the Umbelliferae family, including carrot, parsley and coriander. Other than this, monoenoic isomers with a double bond in an even-numbered position are only rarely encountered.
Other cis-octadecenoic acids, such as 7-, 13- and 15-18:1, are occasionally seen in lipids of fish or marine invertebrates. 5-18:1 is a minor component of the seed oil of meadowfoam and of a few other plant species, and it is encountered in the lipids of sponges.
Trans fatty acids. Tissues of ruminant animals, such as cows, sheep and goats, can contain a number of different 18:1 isomers (and those of 14:1, 16:1 and 17:1) of both the cis and trans-configuration as shown in Table 2. With the cis-isomers, 9- and 11-18:1 predominate as might be expected. 11t-18:1 makes up 50% of the trans-monoenes (which can comprise 10 to 15% of the total monoenes or 3-4% of the total fatty acids), but there are appreciable amounts of other isomers from 7t- to 16t-18:1.
Table 2. Distribution of double bonds in cis and trans-octadecenoates from bovine adipose tissue (wt % of the total in each class).
|Double bond position||cis-18:1||trans-18:1|
|Hay, J.D. and Morrison, W.R. Lipids, 8, 94-95 (1973).|
These are products of the biohydrogenation of linoleic and linolenic acids from herbage by rumen microorganisms. In addition, monoenoic fatty acids with trans configurations have been detected in the membrane lipids of some aerobic bacteria, such as Pseudomonas putida, which have the capacity to synthesise them de novo. In this instance, trans fatty acids are synthesised in the cytoplasmic membrane by isomerization of the analogous double bonds of the cis configuration. Trans-9- and trans-3-18:1 are occasionally reported from seed oils. Otherwise, trans-18:1 isomers are only rarely encountered in natural lipids, although they are present in oils that have been hydrogenated industrially.
10:1 to 17:1 Isomers
9-cis-Decenoic acid is a minor component of cow's milk fat, and 9-12:1 and 9-14:1 are found here also. The last of these is a minor but fairly common constituent of marine oils, and it is occasionally reported from seed oils and bacteria.
4-Decenoic acid has been found in seed oils of the Lauraceae (as has 4-12:1 and 4-14:1). 5- and 7-14:1 have been found in lipids of bacterial or marine origin. Other medium-chain monoenoic isomers have been detected in body fluids as products of beta-oxidation of longer-chain fatty acids and in microbial lipids. Various 15:1 and 17:1 isomers are reported from time to time, especially in microbial lipids or fish oils.
9-cis-Hexadecenoic acid (palmitoleic acid, 9-16:1 or 16:1(n-7)) is a ubiquitous but normally minor component of animal lipids, but it can be much more abundant in fish oils such as cod-liver oil, when it may be accompanied by the 7- and occasionally the 11-isomer. It is also a major constituent of some plant oils such as macadamia nuts or the pulp of sea buckthorn fruit. In animal tissues, it has recently been found to have a distinctive function in mice as a lipokine – a newly coined word to define a lipid hormone, i.e. it is an adipose tissue-derived molecule, which amongst other effects stimulates the action of insulin in muscle. It has been suggested that adipose tissue uses lipokines such as this to communicate with distant organs and regulate metabolism throughout the body. However, it seems that these findings have not been fully supported in human studies, possibly because synthesis of fatty acids de novo is much lower in humans than in mice. It has been argued that a metabolite of palmitoleic acid, such as palmitoleoyl-phosphatidylinositol, may be the active lipokine. Palmitoleic acid is linked very specifically to a conserved serine residue in the Wtn family of proteins (O-acylated proteolipids) and is essential for their function. There is evidence also that palmitoleic acid may serve as a marker for lipogenesis de novo from glucose.
6-cis-Hexadecenoic acid (6-16:1 or ‘sapienic’ acid) is the single most abundant component in human sebum lipids, where it is accompanied by an elongation and desaturation product 5,8-octadecadienoic acid. 6-16:1 occurs also in some seed oils of the Umbelliferae, and the 4-isomer has been detected in some seed oils and marine samples. Some bacteria contain 9t-16:1, which is produced by isomerisation of the cis-isomer, while trans-6-18:1 has been detected in a number of organisms of marine origin.
3-trans-Hexadecenoic acid is an important constituent of the photosynthetic tissues (chloroplasts) of plants, where it is located characteristically in the phosphatidylglycerol fraction, and is presumed to have some specific but as yet undefined biological function.
20:1 to 32:1 Isomers
Very-long-chain monoenoic fatty acids of the (n-9) family occur in a variety of natural sources, often accompanied by analogous fatty acids of the (n-7) family), especially in animal tissues. For example, monoenes from 20:1 to 26:1 are normal constituents of animal sphingolipids. Odd-numbered very-long chain monoenes (23:1 upwards) from brain belong to (n-8) and (n-10) families, presumably because they are formed by chain-elongation of 9-17:1 (17:1(n-8)) and 9-19:1 (19:1(n-10)), respectively (see below). An even wider range of chain-lengths is found in monoenes from plant waxes and sponge lipids, and some of these fatty acids may contain methyl branches in addition to the double bond. .
11-cis-Eicosenoic acid is a common if minor constituent of animal tissues and fish oils, often accompanied by the 13-isomer. It is also found in rapeseed oil and seed oils of related species. cis-5-20:1 can amount to 67% of the total fatty acids in meadowfoam oil.
Similarly, erucic acid (13-22:1) occurs naturally in fish oils and in small amounts in the phospholipids of animal tissues (often with some 15-22:1), but it is probably best known as the major component (up to 66%) of the total fatty acids in rapeseed oil. 5-22:1 is present in meadowfoam oil.
15-cis-Tetracosenoic acid is present in small amounts in phospholipids and especially sphingolipids of animal tissues. It is a major constituent of seed oils of Brassica and Lunaria species. 17-26:1 is found in sphingolipids and in sponges, as well as a few seed oils (Tropaeolum and Ximenia species).
3. Biosynthesis of Monoenoic Fatty Acids
In nearly all higher organisms, including many bacteria, yeasts, algae, plants and animals, double bonds are introduced into fatty acids by an aerobic mechanism that utilizes preformed fatty acids as the substrate. Molecular oxygen and a reduced pyridine nucleotide (NADH or NADPH) are required cofactors. Thus in animals and yeasts, the coenzyme A ester of octadecanoic (stearic) acid is converted directly to oleoyl-CoA by a concerted removal of hydrogen atoms from carbons 9 and 10 (D-stereochemistry in each instance). The stearoyl-CoA desaturase system is in the endoplasmic reticulum membrane with the active centre exposed to the cytosol, and consists of three proteins, cytochrome b5 reductase, cytochrome b5, and the desaturase, which contains two atoms of iron at the active site.
Membrane-bound enzymes are notoriously difficult to purify, but the evidence suggests that the yeast Δ9 desaturase consists of two membrane spanning regions with the bulk of the protein protruding into the cytosol. The enzyme has much in common with hydroxylases and contains eight essential histidine residues that coordinate with the di-iron centre at the active site. The cytochrome b5 component is fused to the desaturase and is believed to facilitate electron transfer from NADH reductase to the catalytic di-iron core.
Palmitoleate is synthesised from palmitate by a similar mechanism. Subsequently, oleate can be chain elongated by two carbon atoms to give longer-chain fatty acids of the (n-9) family, while palmitoleate is the precursor of the (n-7) family of fatty acids. In mammalian systems, the elongases are known to be distinct enzymes that differ from those involved in the production of longer-chain polyunsaturated fatty acids. Alpha- and beta-oxidation can also occur to give shorter chain components of the two families.
In plants, there are two types of fatty acid desaturase, of which the best characterized are soluble enzymes that use preformed fatty acids bound to acyl carrier protein (ACP), rather than to CoA, as the substrate. They occur mainly in the plastid. The enzyme from the castor plant (Ricinus communis) has been particularly well characterized, from its crystal structure by spectroscopy and more recently by molecular biology methods. It is known to consist of two identical monomers, each containing an active site with a di-iron-oxo cluster. The iron is reduced by ferredoxin and molecular oxygen is bound to it, resulting in a complex that can remove hydrogens and electrons in a step-wise manner from carbons 9 and 10 of stearoyl-ACP with formation of a double bond. The crystallographic model of the dimeric enzyme appears to have a potential substrate-binding region, which takes the form of a hydrophobic pocket transversing the protein. Modelling studies suggest that the stearoyl substrate fits into this space particularly well if it adopts a gauche conformation at the C9–C10 positions in the region adjacent to the di-iron core, thus facilitating regio-selective syn-dehydrogenation to produce the oleyl product. It has been described as "a textbook example of a lock-and-key type of binding site".
Other soluble plant desaturases have been characterized that differ in the positional specificity of double bond insertion and substrate chain-length specificity. These are similar in amino acid sequences and in the di-iron binding amino acid motifs to the stearoyl ACP Δ9 desaturase, but they are very different from membrane-bound desaturases. It has been suggested that changes to as few as four amino acid locations in these enzymes can change the regiospecificity of desaturation, probably by altering the presentation of the substrate to the active site. For example, five residues substituted from the castor sequence into the corresponding positions in the Thunbergia sequence converted the Thunbergia Δ6-16:0-ACP desaturase into a Δ9-18:0-ACP desaturase.
Petroselinic acid (6-18:1) in seed oils of the Umbelliferae is synthesised by an enzyme that removes hydrogens from position 4 of palmitate, before the resulting 4-16:1 is elongated by two carbon atoms.
Some plant desaturases are also located in membranes and can utilize substrate fatty acids in various esterified forms, a factor that can influence regiospecificity. For example, the position of desaturation obtained with a bifunctional 7-/9-16:0 desaturase was reportedly controlled by its subcellular targeting to the precursor fatty acid as a component of different lipids in specific organelles. A mechanistic link between desaturases and hydroxylases has been observed in some plant species. It seems probable that the active site in membrane desaturases differs fundamentally in structure from soluble desaturases, perhaps by having a cleft, which substrates enter laterally, rather than a deep binding cavity.
Certain bacteria produce mono-unsaturated fatty acids by an anaerobic mechanism that involves the fatty acid synthetase (see our web page on saturated fatty acids). In Escherichia coli, for example, during the fourth cycle of chain elongation, a branch point occurs in fatty acid synthesis following the dehydrase step. Chain elongation can proceed as normal, or an isomerase, which is in fact the same enzyme as the dehydrase, can convert the trans-2-decanoyl-ACP to cis-3-decanoyl-ACP. The latter is not a substrate for the enoyl-ACP reductase, but it can be further elongated with eventual formation of a cis-11-18:1 fatty acid.
For many years, this was thought to be the characteristic pathway for biosynthesis of unsaturated fatty acids in all bacteria, but it is now recognised that this precise mechanism is restricted to a few proteobacteria, such as E. coli. While the detailed mechanisms and enzymes for most bacterial species have yet to be adequately characterized, others such as the Gram-positive bacteria utilize a variation in the mechanism in which a dedicated trans-2,cis-3-decenoyl-ACP isomerase acts after the dehydration step. Aerobic mechanisms certainly exist also, and Pseudomonas aeruginosa has been shown to have two aerobic desaturase enzymes in addition to an anaerobic system, for example.
4. Nutritional and Metabolic Aspects
The relative proportion of saturated to monounsaturated fatty acids is an important aspect of phospholipid compositions and changes to this ratio have been claimed to have effects on such disease states as cardiovascular disease, obesity, diabetes, neuropathological conditions and cancer. For example, monoenes have been shown to have cyto-protective actions in pancreatic β-cells. cis-Monoenoic acids have desirable physical properties for membrane lipids in that they are liquid at body temperature, yet are relatively resistant to oxidation. They are now recognised by nutritionists as being beneficial in the human diet. For example, oleic acid comprises a high proportion of the fatty acids of olive oil, a major fat component of the ‘Mediterranean diet’. The exception is erucic acid as there is evidence from studies with laboratory rats that it may adversely affect the metabolism of the heart.
The current nutritional view is that dietary trans-monoenoic fatty acids, especially those from industrial hydrogenation processes, should be considered as harmful and in the same light as saturated fatty acids. Detailed discussion of this topic is best left to nutritional experts.
Depending on animal species, various isoforms exist of the stearoyl-CoA desaturase that controls the level of oleic acid production de novo in animals, four in mice and many other vertebrates but only two in humans. In addition to its primary function, at least one of these isoforms (‘SCD1’) activates AMP-activated protein kinase, an enzyme that phosphorylates and deactivates acetyl-CoA-carboxylase, which is important in the regulation both of fatty acid synthesis and of fatty acid oxidation in a reciprocal manner, i.e. by promoting fatty acid synthesis but decreasing oxidation. The sequence of events is complex, but it appears that the anti-obesity hormone leptin inhibits the expression of the gene for stearoyl-CoA desaturase so that levels of this enzyme fall. This in turn leads to inactivation of acetyl-CoA carboxylase and thence to stimulation of fatty acid oxidation and inhibition of fatty acid synthesis. Genetically modified mice that are deficient in SCD1 appear to be protected from obesity, cellular lipid accumulation and insulin resistance. Pharmaceutical companies are actively seeking drugs that will lower the activity of stearoyl CoA desaturase with the hope of producing anti-obesity effects in patients. In addition, there are potential benefits for intervention in the treatment of non-alcoholic fatty liver disease and diabetes
Certain amide derivatives of oleate, such as oleamide and oleoylethanolamide, have highly specific biological functions in animal tissues, as discussed elsewhere on this site.
- Buist, P.H. Fatty acid desaturases: selecting the dehydrogenation channel. Nat. Prod. Rep., 21, 249-262 (2004) (DOI: 10.1039/b302094k).
- Christie, W.W. and Han, X. Lipid Analysis - Isolation, Separation, Identification and Lipidomic Analysis (4th edition), 446 pages (Oily Press, Bridgwater, U.K. and Woodhead Publishing Ltd, Cambridge, U.K.) (2010) - Woodhead Publishing Ltd.
- Destaillats, F., Sébédio, J.L., Dionisi, F. and Chardigny, J.-M. (Editors). Trans Fatty Acids in Human Nutrition (2nd edition), (Oily Press, Bridgwater) (2009).
- Gunstone, F.D., Harwood, J.L. and Dijkstra, A.J. (Editors), The Lipid Handbook (3rd Edition). (CRC Press, Boca Raton) (2007).
- Gurr, M.I., Harwood, J.L. and Frayn, K. Lipid Biochemistry (5th Edition). (Blackwells, London) (2002).
- Hodson, L. and Fielding, B.A. Stearoyl-CoA desaturase: rogue or innocent bystander? Prog. Lipid Res., 52, 15-42 (2013) (DOI: 10.1016/j.plipres.2012.08.002).
- Jenkins, T.C., Wallace, R.J., Moate, P.J. and Mosley, E.E. Recent advances in biohydrogenation of unsaturated fatty acids within the rumen microbial ecosystem. J. Anim. Sci., 86, 397-412 (2008) (DOI: 10.2527/jas.2007-0588).
- Parsons, J.B. and Rock, C.O. Bacterial lipids: Metabolism and membrane homeostasis. Prog. Lipid Res., 52, 249-276 (2013) (DOI: 10.1016/j.plipres.2013.02.002).
- Shanklin, J., Guy, J.E., Mishra, G. and Lindqvist, Y. Desaturases: emerging models for understanding functional diversification of diiron-containing enzymes. J. Biol. Chem., 284, 18559-18563 (2009) (DOI: 10.1074/jbc.R900009200).
- Vance, D.E. and Vance, J. (Editors). Biochemistry of Lipids, Lipoproteins and Membranes (5th Edition). (Elsevier, Amsterdam) (2008) - Several chapters.
- Wu, Y., Li, R. and Hildebrand, D.F. Biosynthesis and metabolic engineering of palmitoleate production, an important contributor to human health and sustainable industry. Prog. Lipid Res., 51, 340-349 (2012) (DOI: 10.1016/j.plipres.2012.05.001).
James Hutton Institute (and Mylnefield Lipid Analysis), Invergowrie, Dundee (DD2 5DA), Scotland.
|© AOCS||Credits/disclaimer||Updated: April 15th, 2013||Author|