Fatty Acids: Straight-Chain Monoenoic

1. Structure and Nomenclature

Structural formulae of cis and trans double bonds 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 occur in nature.

The most abundant monoenoic fatty acids in animal and plant tissues have straight (unbranched) chains with 16 or 18 carbon atoms, but analogous fatty acids with 10 to 36 carbon atoms occur naturally in esterified form, and fifty structurally distinct monoenoic fatty acids have been identified in plants alone. 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 -

Figure 1. cis-9-Octadecenoic acid or oleic acid or 9Z-18:1 or 18:1(n-9).

- is systematically named cis-9-octadecenoic acid, although it is more usual to see the trivial name oleic acid in the scientific literature. In the shorthand nomenclature, it is designated '18:1' (or 9Z-18:1, Δ9-18:1 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 substituents 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, and the (n‑x) nomenclature helps to point out such relationships.

A list of a few monoenoic fatty acids together with their systematic and trivial names and their shorthand designations is given in Table 1, although I prefer to avoid trivial names for all but the most common of these.

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	6-16:1 or 16:1(n-10)
cis-7-hexadecenoic	hypogeic	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 are liquid at room temperature as are triacylglycerols (or oils and fats) containing high proportions of monoenoic fatty acids. Analogous fatty acids with trans double bonds are normally higher melting. Monoenoic fatty acids with branched chains are produced by some bacteria and marine invertebrates (c.f., here..).

2. Occurrence

cis-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. 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 be of nutritional value as part of the Mediterranean diet. Indeed, this acid has many noteworthy biological activities discussed in relation to animal metabolism below, both in the free and esterified form with amides such as oleamide and oleoylethanolamide having their own metabolic properties. In plants, it is reported to influence defence 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 those plants containing appreciable amounts of its biosynthetic precursor, palmitoleate (9-16:1 or 16:1(n-7)). Elongation of palmitoleate is the source of cis-11‑18:1 in animal tissues, but vaccenic acid per se, from the Latin 'vacca' meaning cow and abundant in ruminant fats, is the trans isomer.

Petroselinic acid (6c-18:1) occurs up to a level of 50% or more in seed oils of the Apiaceae (Umbelliferae) family, including carrot, celery, parsley and coriander, and Thunbergia species contain up to 92% of this acid. It is reported to have antidiabetic, antibacterial, and antifungal properties. 10‑18:1 (with 8-16:1) is considered specific for methane-oxidizing bacteria, but apart from these, monoenoic isomers with a double bond in an even-numbered position are only occasionally encountered in nature. Other cis-octadecenoic acids, such as 5, 7, 13 and 15-18:1, are occasionally seen in lipids of fish or marine invertebrates, while 5-18:1 is a minor component of the seed oil of meadowfoam and of a few other plant species.

cis-10:1 to 17:1 Isomers

9-cis-Decenoic acid together with 9-12:1 and 9-14:1 are trace component of cow's milk fat, and the last of these is a minor but 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), while 5- and 7-14:1 have been found in some 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, mostly in microbial lipids or fish oils.

thistle 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 a major constituent of a few plant oils such as macadamia nuts or the pulp of sea buckthorn fruit. In mice, it has recently been found to be a lipokine, a newly coined word to define a lipid hormone, i.e., it is an adipose tissue-derived signalling molecule, which amongst other effects stimulates the action of insulin in muscle (see below), and it is an essential covalent modifier of Wnt proteins. As there is so little in a normal diet, it has been suggested that palmitoleic acid may serve as a marker for lipogenesis de novo from glucose. In plants, it is protective 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 is anti-inflammatory; it may be a biomarker for early detection of cardiovascular disease.

6-cis-Hexadecenoic acid (6-16:1 or 16:1(n-10) or ‘sapienic’ acid) is the single most abundant component in human sebum lipids and may be biocidal, but it is rarely found elsewhere in nature. In sebum, it is accompanied by an elongation and desaturation product 5,8‑octadecadienoic acid. It has been detected in plasma and erythrocytes with increased levels in morbidly obese patients, and although its role in these tissues is not known, it is present in macrophages in mice as well as humans, together with the two other 16:1 isomers. 6-16:1 occurs in some seed oils of the Umbelliferae and in Thunbergia species, and the 4-isomer has been detected in some seed oils and various marine sources. A further isomer, cis‑10‑hexadecenoic acid (10‑16:1), is a component of triacylglycerols in Mycobacterium vaccae, a soil-derived bacterium, and is reported to have anti-inflammatory, immunoregulatory and stress resilience properties.

cis-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) in animal tissues, and those 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 as well as 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. In plants, it is present 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.

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, where its presence is generally considered harmful to consumers (discussed below); edible cultivars lacking erucic acid have been developed. 5-22:1 is a component of meadowfoam oil.

15-cis-Tetracosenoic acid (nervonic) is present in small amounts in phospholipids and especially sphingolipids of animal tissues; the trivial name derives from its occurrence in brain sphingolipids. It is a major constituent of some seed oils, such as Brassica and Lunaria species. 17‑26:1 is found in sphingolipids of animals and in sponges, as well as a few seed oils (e.g., Tropaeolum and Ximenia species).

Trans fatty acids

Although monoenoic fatty acids with double bonds of the trans-configuration are relatively rare in nature, 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. 11-trans-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. With the cis-isomers, 9c- and 11c-18:1 predominate as might be expected. 9-trans-16:1 is formed in animal tissues by β-oxidation of dietary vaccenic acid.

Double bond position	cis-18:1	trans-18:1
Table 2. Distribution of double bonds in cis and trans‑octadecenoates from bovine adipose tissue (wt % of the total in each class).

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); DOI.

These trans-monoenes are products of the biohydrogenation of linoleic and linolenic acids during digestion of herbage by rumen microorganisms (see below) before they are taken up into the tissues of the animal and find their way into meat and dairy products. 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 existing double bonds of the cis configuration by an enzyme of cytochrome-c type, presumably to modify the physical properties of the lipids in membranes to make them more rigid in response to environmental stress. trans-18:1 isomers are often present in commercial seed oils as a by-product of industrial hydrogenation of the latter to reduce their propensity to oxidation in foods.

3-trans-Hexadecenoic acid is a constituent of the photosynthetic tissues (chloroplasts) of plants, where it is located characteristically in the phosphatidylglycerol fraction, and it is presumed to have some as yet undefined minor function, as Arabidopsis mutants that lack this fatty acid appear to grow normally. 9-trans- and 3‑trans-18:1 are occasionally reported from seed oils. Some bacteria contain 9t-16:1, which is produced by isomerization of the cis-isomer, while trans-6-18:1 has been detected in several organisms of marine origin.

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 aerobic desaturation mechanisms that utilize preformed fatty acids as the substrates. Desaturase enzymes are oxygenases that can remove two protons from adjacent carbon atoms in a hydrocarbon chain to create a carbon-carbon double bond. A different mechanism for formation of monoenoic fatty acids is present in simple proteobacteria as discussed below.

Animals and Yeasts: Depending on species, there are many membrane-bound stearoyl-CoA (Δ9-desaturase (SCD) isoforms that share considerable sequence homology and with overlapping but characteristic tissue specificities. In humans, there are two isoforms with SCD1 expressed in adipose tissue, liver, lungs, brain and heart predominantly, while SCD5 is expressed mainly in the brain and pancreas. The latter shares limited homology with rodent isoforms (four in mice, SCD1 to 4) and was once thought to be unique to primates but has now been found in other vertebrates, including ruminants, pigs, dogs and birds. Human SCD1 can utilize saturated acyl-CoAs with an acyl chain length of 14 to 19 carbons as substrates but favours octadecanoyl-CoA (stearoyl or 18:0-CoA) over others. In mice, SCD2 is expressed ubiquitously and is the main isoform in the brain, although it is induced by high-fat diets in adipose tissue, lung and kidney; it produces palmitoleoyl-CoA and oleoyl-CoA, while SCD3 prefers palmitoyl-CoA as substrate. In other species, isoforms of desaturases can have differing fatty acyl specificities.

The CoA ester of octadecanoic 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 SCD1 in complex with its substrate stearoyl-CoA in the endoplasmic reticulum, it has been shown that there is a cytosolic domain containing a di‑metal catalytic centre consisting of two iron cations that are coordinated by nine conserved histidine residues and one water molecule, while four trans-membrane alpha-helices form a hydrophobic core. 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 that enable the acyl-chain to enter a hydrophobic tunnel, which extends to the interface of the cytoplasmic and transmembrane domains with its shape determining 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 with the oxygen activated at the di-iron centre and reduced to water, while the ferrous catalytic centre is regenerated by transfer of electrons from cytochrome b₅.

Figure 2. Desaturation of stearoyl-coA to oleoyl-CoA in animals.

Inhibition of the desaturase by its product is possible, but normally this is rapidly removed in vivo by membrane-bound acyltransferases so is not an issue. In the yeast, Saccharomyces cerevisiae, the Δ9-desaturase Ole1 forms a supercomplex with some of the acyltransferases responsible for glycerolipid synthesis. In animals, SCD1 is known to be tightly regulated by hormones and many other cellular and dietary factors, and for example, this isoform 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. In RAW macrophages, SCD1 can produce minor amounts of odd-chain monounsaturated fatty acids with n-6, n-8, and n-10 double bonds, as well as n-5, n-7, and n-9 families of even-chain isomers. At the transcriptional level, it is regulated mainly by sterol responsive element binding protein SREBP-1c, which also induces the expression of other enzymes for fatty acid biosynthesis de novo, i.e., Δ5, Δ6 and Δ9 desaturases and ELOVL6. Other transcription factors include the liver X receptor and peroxisomal proliferator-activated receptors (PPARs), while SCD1 is controlled by rapid proteolytic cleavage. Stearoyl‑CoA desaturases in turn control many aspects of lipid metabolism as is discussed below.

Palmitoleate is synthesised from palmitate by a similar mechanism via the stearoyl-CoA desaturase, but sapienic acid (6-16:1) is produced by the action of a different enzyme, Δ6 desaturase (FADS2), normally associated with desaturation of linoleic acid (see our web page on polyunsaturated fatty acids). It appears that there are tissue-specific mechanisms in the human sebaceous gland to enable FADS2 to act in this way, including a reduction in competing desaturase activity. In certain cancer cells, 8-18:1 can be produced by this mechanism when uptake of fatty acids of exogenous origin is inhibited, while a Δ11 double bond can be introduced by this enzyme in odd-chain fatty acids in RAW macrophages.

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, while palmitoleate (9-16:1 or 16:1(n-7)) is the precursor of the (n-7) family of fatty acids. In mammalian systems, the elongases differ from those for the production of longer-chain polyunsaturated fatty acids, and elongases (ELOVL proteins) in general are discussed in our web page dealing with saturated fatty acids. Of the seven elongation iso-enzymes, ELOVL1, 3, 4, 6 and 7 participate in the elongation of monounsaturated fatty acids, but with differing tissue locations and substrate requirements; ELOVL4 is responsible for the production of the C₂₄ and longer-chain fatty acids in sphingolipids. In contrast, alpha- and beta-oxidation can occur to give shorter chain fatty acids of the two monoene families.

Figure 3. Biosynthesis of the n-9 and n-7 families of monoenoic fatty acids.

Plants: There are two unrelated types of fatty acid desaturase (with multiple isoforms) in higher plants that are involved in the synthesis of monoenoic fatty acids, i.e., soluble acyl-acyl carrier protein (ACP) desaturases and membrane-bound desaturases, both of which are di‑iron-oxo enzymes with a dimeric quaternary structure. Those most studied are the soluble enzymes that occur mainly in the plastid and use preformed fatty acids bound to ACP, rather than to CoA, as the substrate. The crystal structure of the enzyme from the castor plant (Ricinus communis) has been characterized by spectroscopy and molecular biology methods and consists of two identical monomers, each containing a catalytic site with a di-iron-oxo cluster and a potential substrate-binding region, which takes the form of a hydrophobic pocket traversing the protein. 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 stepwise manner from carbons 9 and 10 of stearoyl-ACP with formation of a double bond. By means of modelling studies, it has been suggested that the stearoyl substrate fits into the hydrophobic pocket 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 (sometimes described as "a textbook example of a lock-and-key type of binding site").

The structures of other soluble plant desaturases that differ in the positional specificity of double bond insertion and the chain-length of the substrate have been determined, and these are responsible for the biosynthesis of the many unusual fatty acids found in plants. As they are similar in amino acid sequences and in the di-iron binding amino acid motifs to the stearoyl ACP Δ9‑desaturase, 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 catalytic site. For example, five residues substituted from the castor sequence into the corresponding positions in the Thunbergia sequence converted Δ6-16:0-ACP desaturase of the latter into a Δ9‑18:0‑ACP desaturase. A mechanistic link between desaturases and hydroxylases has been observed in some plant species.

Those plant desaturases located in membranes are very different from cytosolic desaturases, and that in the endoplasmic reticulum uses cytochrome b₅ reductase as the flavoprotein with cytochrome b₅ as the electron carrier. They can often utilize substrate fatty acids in various esterified forms, a factor that can influence regiospecificity, as 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 glycerolipids in each organelle. Some species of cyanobacteria have Δ9 desaturases (Des or acyl-lipid desaturases) that act upon stearic acid esterified to position sn-1 of glycerophospholipids, while others require the substrate in positions sn-2. With membrane desaturases, it seems probable that the catalytic site differs fundamentally in structure from soluble desaturases, perhaps by having a cleft, which substrates enter laterally, rather than a deep binding cavity. These desaturases in cyanobacteria and plants participate in remodelling lipids to change membrane fluidity in response to temperature variation and other abiotic stresses.

A Δ6-stearoyl-acylcarrier protein (18:0-ACP) desaturase from Thunbergia laurifolia in plastids responsible for the biosynthesis of petroselinic acid (6‑18:1) has been characterized and shown to differ from the archetypal Δ9-18:0-ACP desaturase by mutations in key amino acids. In seed oils of the Umbelliferae, a different mechanism operates in which this fatty acid is synthesised by a desaturase that removes hydrogens from position 4 of palmitoyl-ACP before the resulting 4-16:1 is elongated by two carbon atoms to produce 6-18:1. After release of the free acid by a thioesterase, it is transferred to the endoplasmic reticulum and converted to the CoA ester for incorporation into triacylglycerols. Sequential two-carbon elongation of monoenoic acids by elongases in this manner is a common method of altering the positional distribution of double bonds relative to the carboxyl group in hydrocarbon chains in plants as in animals.

Figure 4. Biosynthesis of petroselinic acid in the Umbelliferae.

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.

Bacteria: Several routes to the production of monoenoic fatty acids in bacteria are known, but most species produce these by anaerobic mechanisms that utilize the fatty acid synthetase II (FAS II), in which the various enzymes in the process are dissociated (as discussed in greater detail in our web page on saturated fatty acids). In brief, there are four enzymatic reactions in each iterative cycle of chain elongation, and in the first step, 3-ketoacyl-ACP synthase I (FabB) or II (FabF) adds a two-carbon unit from malonyl-ACP to the growing acyl-ACP, before the resulting keto ester is reduced by a NADPH-dependent 3-ketoacyl-ACP reductase (FabG). The elements of water are removed by a 3-hydroxyacyl-ACP dehydratase (FabA or FabZ), before the last step in which an enoyl-ACP reductase (FABI or FabK) generates the saturated acyl-ACP.

In the much-studied facultative anaerobe Escherichia coli, the double bond in monoenes is generated at a branch point in fatty acid synthesis at the dehydratase step during the fourth cycle of chain elongation. Instead of chain elongation proceeding as normal, an isomerase converts the trans-2-decenoyl-ACP to cis-3-decenoyl-ACP. Of the two hydratases, FabZ can catalyse dehydration only, while FabA is bifunctional and carries out both dehydration and isomerization. cis-3-Decenoyl-ACP 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 exist with FabF being the most common, while FabB is important for the introduction of the double bond. FabF is responsive to temperature and may regulate the degree of unsaturation and thence fluidity of membranes in an organism. The reaction is terminated by acyltransferases, such as the glycerol-3-phosphate acyltransferase, which transfers the fatty acyl group to a complex lipid.

Figure 5. 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 are known to utilize a variation in the mechanism in which a dedicated trans-2,cis‑3-decenoyl-ACP isomerase acts after the dehydration step. Streptococcus pneumoniae introduces the double bond by means of a such an enzyme (FabM), which bears no structural similarity to FabA, although it utilizes the same substrate.

Aerobic mechanisms exist in some bacteria, and Pseudomonas aeruginosa has been shown to have two aerobic desaturase enzymes as well as an anaerobic system. One of these is a membrane-associated Δ9‑desaturase, which is capable of regioselective cis dehydrogenation through activation of molecular oxygen with a diiron cluster at the catalytic site and introduces a double bond into the Δ9‑position of fatty acyl chains attached to the sn-2 position of existing glycerophospholipids; the other reacts in the same way with acyl-CoA produced from exogenous saturated fatty acids. Bacillus subtilis has a Δ5-acyl desaturase, which is an integral membrane protein with a di-iron unit held by three histidine clusters and utilizes ferredoxin and flavodoxins as electron donors.

Rumen metabolism: Dietary fatty acids such as linoleic acid are subjected to biohydrogenation by bacteria in the rumen of cows, goats and sheep (ruminant animals). Many different organisms are present and produce many different products by mechanisms that are still poorly understood, but a major route involves the isomerization of the cis double bond in position 12 to form conjugated octadec-cis-9,trans-11-dienoic (rumenic) acid (this step is discussed further in our web page on conjugated fatty acids), which undergoes biohydrogenation to yield octadec-trans-11-enoic (vaccenic) acid. Both fatty acids are taken up by the host animals and find their way into meat and dairy products.

Figure 6. Biohydrogenation of linoleic acid by rumen microorganisms.

As described briefly above, some bacteria can directly isomerize existing cis-double bonds to the trans-configuration, and this be a further mechanism with rumen bacteria.

Catabolism: Most unsaturated fatty acids are broken down in animal tissues to produce energy by the multi-step process of β‑oxidation, as discussed in our web page on carnitines.

4. Chemical Reactivity

Monounsaturated fatty acids are much less reactive than polyunsaturated toward autoxidation, a process discussed in relation to tocopherols and elsewhere in these pages, but they are not immune. There is an initial abstraction of a hydrogen atom during initiation to form a radical at either of the allylic positions, which correspond to carbons 8 and 11 of oleic acid, to form (Z)-peroxyl radicals by reaction with oxygen. Both allylic radicals have resonance forms that can form (E)‑peroxyl radicals, i.e., some geometrical and positional isomerization of the double bond occurs. Propagation of the reaction and eventual termination can then take place as in more unsaturated systems.

Figure 7. Chemical reactivity of monoenoic fatty acids with oxidizing agents.

Isomerization of isolated double bonds from the Z to E configuration can occur rapidly in the presence of thiyl radicals, without double bond migration, and the same reaction can occur more slowly with nitrogen radicals. With the latter, there can be some addition to the double bond to form nitro fatty acids.

5. Nutritional and Metabolic Aspects

The relative proportion of saturated to monounsaturated fatty acids is an important aspect of phospholipid composition and changes to this ratio have been claimed to influence such disease states as cardiovascular disease, obesity, diabetes, liver dysfunction, intestinal inflammation, neuropathological conditions and cancer. In human metabolic disease, for example, there are increased ratios of 18:1 and 16:1 fatty acids relative to the saturated precursors, while in diabetes, 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 recognized by nutritionists as being beneficial in the human diet, and oleic acid comprises a high proportion of the fatty acids of olive oil, a major fat component of the ‘Mediterranean diet’, which is generally considered to be a healthy one with a diminished incidence of cardiovascular disease and cancer.

The exception is erucic acid (13-22:1) because studies with laboratory rats in the 1970s showed that it could adversely affect the metabolism of the heart. As rapeseed oil was a major dietary source for humans, low erucic oils such as 'Canola' were developed to circumvent the problem. There have apparently been no studies to confirm the toxicity of erucic acid in humans or other primates, and it has since been argued that the rat studies were flawed. Meantime, erucic acid has been used as a major component of 'Lorenzo's oil' to treat adrenoleukodystrophy with no apparent harm, and there are reports that dietary nervonic acid (15-24:1) may be of benefit in demyelinating diseases.

Although monoenoic fatty acids are abundant in the diet, stearoyl-CoA desaturase (SCD1) controls the level of oleic acid production de novo in animals and determines body adiposity and lipid partitioning. It is a critical regulator of innumerable physiological processes, including energy homeostasis, development, autophagy, tumorigenesis and inflammation. Aberrant transcriptional and epigenetic activation of SCD1 promotes proteins that cause aberrant lipid accumulation thus enhancing the progression of obesity, non-alcoholic fatty liver disease, diabetes and cancer. When the activity of the enzyme is high, fat storage is favoured, but when it is low, metabolic pathways that promote the burning of fat are induced together with decreased lipid synthesis in adipose tissue and liver. In brown adipose tissue, SCDI activity is significantly increased during long-term cold exposure, and by stimulating the release of norepinephrine, this sustains thermogenesis. Insulin-signalling components are upregulated in SCD1 deficiency with effects upon glycogen metabolism in insulin-sensitive tissues. SCD1 stimulates AMP-activated protein kinase, an enzyme that phosphorylates and deactivates acetyl-CoA-carboxylase, which regulates both fatty acid synthesis and oxidation in a reciprocal manner, i.e., by promoting fatty acid synthesis but decreasing oxidation. In the heart, loss of SCD1 is protective under conditions of a high-fat diet as it reduces fatty acid oxidation and increases glucose oxidation, but it can predispose individuals to atherosclerosis under conditions of hyperlipidemia.

thistle The range and sequence of cellular events are 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, leading to inactivation of acetyl-CoA carboxylase and thence to promotion of fatty acid oxidation and inhibition of fatty acid synthesis. Genetically modified mice that are deficient in the SCD1 isoform appear to be protected from cellular lipid accumulation and obesity, and they have increased insulin sensitivity. It has been reported that in hepatocytes, but not adipocytes, oleic acid feeding increases the number and size of lipid droplets while simultaneously inhibiting lipogenesis.

Unesterified oleic acid is an endogenous ligand for the orphan nuclear receptor TLX/NR2E1, which governs neural stem and progenitor cell self-renewal and proliferation, and as a result, it is essential for the survival of neural stem cells. This fatty acid can also block the calcium-activated chloride channel TMEM16A/ANO1 in membranes with the potential for a beneficial impact on the cardiovascular system; in brown adipose tissue, it is a ligand for GPR3, which promotes thermogenesis. Indeed, oleic is known to interact with a wide range of receptors, including GPR40 (FFAR1), GPR120 (FFAR4), PPARγ, LXR and EGFR, and it is apparent that as a non-chiral molecule with rotatable bonds, it can adopt a range of diffuse conformations when bound to different macromolecules to influence their behaviour. High expression of oleoyl-ACP hydrolase is a major factor in life-threatening respiratory viral diseases, including influenza, COVID-19 and respiratory syncytial virus.

It has long been known that cancer cells and tumours synthesise lipids at a high rate with an aberrant pattern of fatty acids, including a preponderance of saturated and monoenoic species, and constitutive activation of fatty acid synthesis with Δ9-desaturation de novo is a metabolic hallmark in most cancer cells. This is driven by a requirement for lipids, especially phospholipids, for new membranes and is accomplished by a dynamic sequence of reactions utilizing all the enzymes for fatty acid synthesis including SCD1. SCD1 is also a factor in the molecular pathways of cell survival, especially towards autophagy and apoptotic and non-apoptotic cell death. As it is believed that SCD1 is a central regulator of the complex metabolic and signalling events that control the development of cancer cells, it has been suggested that the development of SCD1 inhibitors might be an alternative treatment for various forms of cancer such as the chemo-resistant malignancies.

Likewise, pharmaceutical companies are seeking drugs that will inhibit SCD1 with the hope of producing anti-obesity effects in patients, and there are potential benefits for intervention in the treatment of non-alcoholic fatty liver disease and diabetes. SCD1 is a factor in autoimmunity, and by suppressing the differentiation of regulatory T cells, it is hope that pharmacological inhibitors of SCD1 may have further value for inhibition of autoimmunity and to reduce neuroinflammation.

SCD2 is crucial for mouse development and metabolism, but influences the pathology of obesity, chronic kidney disease and various neurological diseases. The gene for the synthesis of SCD5 is located on a different chromosome from that for SCD1, so presumably there is some different requirement. Palmitic acid may be the preferred substrate in brain, but not in all tissues, and SCD5 is believed to be a special factor for brain development in infants, and there is evidence of some involvement in disease states.

Certain amide derivatives of oleate, such as oleamide and oleoylethanolamine, have well defined functions in animal tissues, while 2‑oleoylglycerol is a signalling molecule in the intestines, as discussed elsewhere on this site. 1,2-Dioleoyl-phosphatidylinositol is signalling lipid, derived from the action of the stearoyl-CoA desaturase (SCD1), and acts as a lipokine to respond to stresses that promote protein degradation, apoptosis and autophagy.

From studies largely with mice, it has been suggested that adipose tissue uses lipokines such as 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 hepatic lipogenesis in steatosis (or 'fatty liver') by the inhibition of SCD1 and triacylglycerol synthesis. Higher concentrations in plasma from exogenous administration are strongly associated with insulin sensitivity, independently of age, sex and adiposity in healthy humans, but they are not associated with decreased obesity; rather its concentration is elevated in plasma of obese patients. In macrophages, palmitoleate generation is reported to alleviate lipotoxicity-induced stress in the endoplasmic reticulum with a reduction in apoptosis and benefits towards the progression of atherosclerosis. Oral supplements reportedly improve the skin barrier. It may be relevant that palmitoleic acid is linked to a conserved serine residue in the Wnt family of proteins necessary for tissue development, and it is essential if they are to carry out their role in tissues. Its elongation product, cis-vaccenic acid, is reported to have its own functions, and other 16:1 isomers are reported to be beneficial to consumers.

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, possibly because they enhance intracellular signalling pathways that induce inflammation and cell death under conditions of metabolic stress. That said, there is a school of thought that natural trans-fatty acids such as those found in ruminant meat and dairy products are broadly neutral towards health, possibly because the main isomer, vaccenic acid (11t-18:1) can be converted in tissues to conjugated linoleic acid (octadec-9-cis,11-trans-dienoic or 9c,11t-18:2). Similarly, trans-palmitoleic acid (9t-16:1), possibly formed by retroconversion of vaccenic acid, is reported to be protective towards the risk of type 2 diabetes. Detailed discussion of this topic is best left to nutritional experts of whom I am not one.