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Fatty Acids: Straight-Chain Monoenoic



1.  Structure and Nomenclature

Structural formulae of cis and trans double bondsStraight- 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 -

Structural formula of oleic acid

- 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 systematic and trivial names and their shorthand designations is given in Table 1. However, trivial names are best avoided for all but the most common of these fatty acids.

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-6-hexadecenoic sapienic acid 6-16:1 or 16:1(n-10)
   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)
 
   trans-3-hexadecenoic 3t-18:1
   trans-9-octadecenoic elaidic 9t-18:1
   trans-11-octadecenoic vaccenic 11t-18:1
 

A cis-double bond in a fatty acid introduces a 30° bend in the alkyl chain, and this tends 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.


2.  Occurrence

18:1 Isomers

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 to 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 in relation to animal metabolism below, both in the free and esterified form. For example, of the many esterified forms, oleamide and oleoylethanolamide have especially important biological activities. In plants, it is reported to be involved in defense signalling against bacterial and fungal pathogens by upregulating the expression of genes that regulate nitric oxide production. 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 or 16:1(n-7), e.g. the fruit of the sea buckthorn plant. Note that vaccenic acid per se should strictly speaking be applied only to 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, while 10-18:1 (with 8-16:1) is considered specific for methane-oxidizing bacteria. Other than these examples, 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 (vaccenic) makes up 50% of the trans-monoenes, which can comprise 10 to 15% of the total monoenes or 3 to 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
 
7 1 1
8 1 2
9 85 5
10 2 12
11 9 47
12 2 6
13 7
14 7
15 6
16 8
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 before they are taken up into the tissues of the animal. 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 is present in seed oils of the Lauraceae (as has 4-12:1 and 4-14:1). 5- and 7-14:1 Fatty acids 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, while 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 (see below). It is also an essential covalent modifier of Wtn proteins. In plants, it has protective effects against certain fungal pathogens. The isomeric cis-7-hexadecenoic acid (7-16:1 or 16:1(n-9)) is reported to be enriched in the lipids of foamy monocytes and shows significant anti-inflammatory activity; it may be a biomarker for early detection of cardiovascular disease.

thistle6-cis-Hexadecenoic acid (6-16:1 or ‘sapienic’ acid) is the single most abundant component in human sebum lipids and has biocidal properties; it has also been found in plasma and erythrocytes with increased levels in morbidly obese patients. In sebum, 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 isomerization 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 sphingolipids from both animals and plants. Odd-numbered very-long-chain monoenes (23:1 upwards) from brain belong to the (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. Monoenes of the (n-5) family (16:1 to 24:1) are utilized for the biosynthesis of the anacardic acids in plants.

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, while 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 native rapeseed oil (not the edible cultivars). 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, but 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 (e.g. Tropaeolum and Ximenia species).


3.  Biosynthesis of Monoenoic Fatty Acids

In nearly all higher organisms, including many bacteria, yeasts, algae, protozoa, plants and animals, double bonds are introduced into fatty acids by an aerobic mechanism that utilizes preformed fatty acids as the substrate. However, simple proteobacteria have a different mechanism.

Animals and Yeasts: Depending on species, there are many membrane-bound stearoyl-CoA desaturase (SCD) isoforms that share considerable sequence homology and with overlapping but distinct tissue specificities. For example, there are two isoforms in humans (four in mice), with SCD1 expressed in adipose tissue, liver, lungs, brain and heart predominantly, while SCD5 is expressed mainly in the brain and pancreas. The coenzyme A ester of octadecanoic (stearic) acid is converted directly to oleoyl-CoA by these enzymes by a concerted removal of hydrogen atoms from carbons 9 and 10 (D-stereochemistry in each instance). There are three components to the desaturase complex: a flavoprotein, NADH cytochrome b5 reductase, a haem-containing protein, cytochrome b5, and the desaturase itself, and they are believed to be situated next to each other in membranes. From X-ray studies of human SCD-1 in complex with its substrate stearoyl-CoA, it has been shown that there is a cytosolic domain containing a di-metal active center, consisting of two iron cations that are coordinated by histidine residues and one water molecule, and four trans-membrane alpha-helices as a hydrophobic core in the endoplasmic reticulum.

Acyl-CoA substrates bind to the surface of the cytoplasmic domain both by hydrogen bonding and by ionic interactions between the phosphates of CoA and the positively charged surface of the enzyme. The acyl-chain enters a hydrophobic tunnel that extends to the interface of the cytoplasmic and transmembrane domains, and its shape determines the positional specificity of the enzyme and the cis-conformation of the product. Molecular oxygen and a reduced pyridine nucleotide (NADH or NADPH) are required cofactors. The oxygen is activated at the di-iron center and reduced to water, while the ferrous catalytic center is regenerated by transfer of electrons from cytochrome b5.

Desaturation of stearic to oleic acid

The activity of the SCD1 enzyme especially is known to be tightly regulated by hormones and many other cellular and dietary factors. For example, SCD-1 is induced by insulin and repressed by leptin, the hormone derived from adipocytes that suppresses appetite and regulates energy homeostasis and many aspects of lipid metabolism. At the transcriptional level, it is regulated by sterol responsive element binding protein (SREBP)-1c as major transcription factor, which also induces the expression of enzymes of for fatty acid biosynthesis de novo. Other transcription factors include the liver X receptor and peroxisomal proliferator-activated receptors (PPARs). In addition, the activity of SCD-1 activity is controlled by rapid proteolytic cleavage. Stearoyl CoA desaturase activity in turn controls many aspects of lipid metabolism as is discussed below.

Chain Elongation: Subsequently, oleic and other monoenoic fatty acids can be chain elongated by two carbon atoms to give longer-chain fatty acids of the (n-9) family. Palmitoleate is synthesised from palmitate by a similar mechanism via the stearoyl-CoA desaturase, and it 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, and the general properties of elongases (ELOVL proteins) are discussed in our web page dealing with saturated fatty acids. Of the seven elongation iso-enzymes, ELOVL1, 3, 4, 6 and 7 are involved in the elongation of monounsaturated fatty acids, but with differing tissue locations and substrates specificities. For example, ELOVL4 is responsible for the production of the C24 and longer-chain fatty acids in sphingolipids.

Biosynthesis of the n-9 and n-7 families of monoenoic fatty acids

In contrast, alpha- and beta-oxidation can also occur to give shorter chain fatty acids of the two monoene families.

Plants: There are two types of fatty acid desaturase in plants, 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.

Biosynthesis of petroselinic acid

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. Little is known of the mechanism of formation of trans-3-16:1 in plants, other than it requires molecular oxygen, while palmitic acid esterified to phosphatidylglycerol is the probable substrate.

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.

Bacteria: Certain bacteria produce mono-unsaturated fatty acids by an anaerobic mechanism that involves the fatty acid synthetase (FAS II - see our web page on saturated fatty acids). In the facultative anaerobe 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 (i.e. it is bifunctional), 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. Different isoforms of the condensing enzyme (Fab) are required at each stage: Fab A for the first 4 cycles, Fab B for 2 cycles with the unsaturated intermediate, and Fab F for the last cycle to convert the 11-16:1 intermediate to 11-18:1. Fab F is responsive to temperature and may regulate the degree of unsaturation and thence fluidity of membranes in the organism. The reaction is terminated by the activity of acyltransferases, such as the glycerol-3-phosphate acyltransferase.

Biosynthesis of monoenoic fatty acids in bacteria

For many years, this was thought to be the characteristic pathway for biosynthesis of unsaturated fatty acids in all bacteria, but it is now recognized 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. One of these is a membrane-associated Δ9-desaturase, which introduces a double bond into the Δ9-position of fatty acyl chains attached to the sn-2 position of existing glycerophospholipids; the other reacts similarly with acyl-CoA produced from exogenous saturated fatty acids.

Catabolism: Most fatty acids are broken down in animal tissues to produce energy by a multi-step process of β-oxidation. This is discussed in our web page on carnitines.


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. In human metabolic disease, there are increased ratios of 18:1 and 16:1 fatty acids relative to the saturated precursors. 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 recognized 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 of whom I am not one.

thistleAlthough monoenoic fatty acids are abundant in the diet, stearoyl-CoA desaturase controls the level of oleic acid production de novo in animals and is an important regulator of body adiposity and lipid partitioning. When the activity of the enzyme is high, fat storage is favoured, but when its activity is low metabolic pathways that promote the burning of fat are activated together with decreased lipid synthesis in adipose tissue and the liver. Thus, insulin-signaling components are upregulated in SCD1 deficiency with effects upon glycogen metabolism in insulin-sensitive tissues. Similarly, 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 cellular lipid accumulation and obesity and they have increased insulin sensitivity. There is a high degree of homology between SCDI in mice and humans, but the second human isoform (‘SCD5’) appears to be specific to primates. 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. It is also believed that SCD1 is a central regulator of the complex metabolic and signalling events that control the development of cancer cells, suggesting that the development of SCD inhibitors may be an alternative treatment for various forms of cancer, especially the chemo-resistant types of malignancies.

From studies with mice, it has been suggested that adipose tissue uses lipokines such palmitoleic acid (9-16:1) to communicate with distant organs and regulate metabolism throughout the body. The proposal is that palmitoleic acid synthesised in adipose tissue stimulates muscle insulin action and suppresses steatosis ('fatty liver') by the inhibition of SCD1 activity and triacylglycerol synthesis in the liver. 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. Also, there is a suggestion that a metabolite of palmitoleic acid, such as palmitoleoyl-phosphatidylinositol, may be the active lipokine. It may be relevant that palmitoleic acid is linked very specifically to a conserved serine residue in the Wtn family of proteins (O-acylated proteolipids), involved in adipose tissue development, and is essential for their function. There is evidence also that palmitoleic acid may serve as a marker for lipogenesis de novo from glucose.

Certain amide derivatives of oleate, such as oleamide and oleoylethanolamide, have highly specific biological functions in animal tissues, while 2‑oleoylglycerol has a signalling function in the intestines, as discussed elsewhere on this site.


Recommended Reading


I can also recommend the chapter on fatty acid biosynthesis in the book - Gurr, M.I., Harwood, J.L., Frayn, K.N., Murphy, D.J. and Michell, R.H. Lipids: Biochemistry, Biotechnology and Health (6th Edition). (Wiley-Blackwell) (2016).



Lipid listings Credits/disclaimer Updated: September 13th, 2017 Author: William W. Christie LipidWeb icon