Cyberlipid

 

 


MONOENOIC FATTY ACIDS

 

In his classic studies on fatty acids from pork fat, Chevreul (1823) recognized the nature of oleic acid but it was not prepared in pure condition for  a long time. Its structure was not definitively elucidated by a series of complex chemical reactions until later (Baruch J, Ber 1894, 27, 172). Much simpler proof of the now accepted structure of oleic acid was given by means of oxidation techniques (Edmed FG, J Chem Soc 1898, 73, 627). The  ozonisation method for the determination of the position of the unsaturated linkage was used for the first time in lipidology in 1903 (Molinari E, Annuario della Soc Chimica di Milano 1903, 9, 507). Oleic acid synthesis was realized in 1934 (Noller CR et al., J Am Chem Soc 1934, 56, 1563).

 

Mono-unsaturated normal fatty acids are widespread in the living world where they occur mostly as the cis-isomer.  Over a hundred naturally occurring monoene fatty acids have been identified. They have the general structure:

 

CH3(CH2)xCH=CH(CH2)yCOOH


The most frequently they have an even number of carbon atoms and the unique double bond may be in a number of different positions.
 The double bond can exist in two stereoisomeric forms : 

 

 

 

 

 

CIS-MONOENOIC FATTY ACIDS

 

The commonest cis-monoenes are of the n-9 series, as oleic acid from olive oil (cis-9-octadecenoic acid) and from quite all seed oils


Some important monoenoic acids are found below:

 

 

Systematic name

Trivial name

Shorthand designation

Molecular wt.

Melting point (°C)

cis-4-decenoic obtusilic 10:1 (n-6) 170.3  
cis-9-decenoic caproleic 10:1 (n-1) 170.3  
cis-5-dodecenoic 5-lauroleic (denticetic) 12:1 (n-7) 198.4  
cis-4-dodecenoic linderic 12:1 (n-8) 198.4  
cis-9-tetradecenoic

myristoleic

14:1 (n-5)

226.4

cis-5-tetradecenoic physeteric 14:1 (n-9) 226.4  
cis-4-tetradecenoic tsuzuic 14:1 (n-10) 226.4  
cis-9-hexadecenoic

palmitoleic

16:1 (n-7)

254.4

0.5

cis-6-hexadecenoic sapienic 16:1 (n-10) 254.4  
cis-6-octadecenoic

petroselinic

18:1 (n-12)

282.4

30

cis-9-octadecenoic

oleic

18:1 (n-9)

282.4

16.2

tr-9-octadecenoic  elaidic tr18:1 (n-9) 282.4 43.7
cis-11-octadecenoic

vaccenic (asclepic)

18:1 (n-7)

282.4

39

cis-9-eicosenoic

gadoleic

20:1 (n-11)

310.5

25

cis-11-eicosenoic

gondoic

20:1 (n-9)

310.5

cis-11-docosenoic cetoleic 22:1 (n-11) 338.6  
cis-13-docosenoic

erucic

22:1 (n-9)

338.6

33.4

cis-15-tetracosenoic

nervonic

24:1 (n-9)

366.6

39

 

 

  • Oleic acid is probably the most common fatty acid (olive oil has a high content of this acid: about 60-70%, but it is also found in a large range of nuts). It is found also in seeds such as in Moringa oleifera seeds, a tree cultivated in all tropical and subtropical regions such as Pakistan, Arabia, Central America, North and the South Philippines, Cambodia, Caribbean Islands, and Africa (Saa RW et al., Food Sci Nutr 2019, 7, 1911).
    The major sources for human food are palm, rapeseed, soybean, butter, lard and tallow.

oleic acid

 


While this common fatty acid is mainly found acylated in glycerides, it may be found sometimes as ethyl esters in organs of animal treated with ethanol (Hungund BL et al., J Chem Pharmacol 1988, 37, 3001) and may serve as markers of ethanol intake. (Laposata M, Prog Lipid Res 1998, 37, 307).
The first synthesis of oleic acid appeared in the literature in 1934 (Noller CR et al., J Am Chem Soc 1934, 56, 1563).
Ethyl oleate was identified as a primer pheromone in honey bees in causing a delayed onset of foraging in younger individuals (Leoncini I et al., PNAS 2004, 101, 17559).

 

  • Myristoleic acid is found in most animal depot fats from marine or terrestrial origin. It represents a major component of seed oil from Myristicaceae, some plant species containing up to 30 per cent of this fatty acid in addition to more important amounts of myristic acid. An isomeric form of myristoleic acid was discovered in dolphin and whale head oils (Tsujimoto M, Chem Umschau 1925, 32, 202) and was proved to be the 5-tetradecenoic acid. This uncommon (n-9) fatty acid was more recently described in the retina, acylating an NH2 terminus  of a protein (recoverin) related to signal transduction in photoreceptors (Dizhoor AM et al., J Biol Chem 1992, 267, 16033). Furthermore, more recently, the presence of this fatty acid in plasma was shown to be of diagnostic value in patients with defects of long-chain fatty acid oxidation (Onkenhout W et al., Clin Chem 1995, 41, 1467).   
  • Palmitoleic acid is found mainly in animal fats, particularly in fish and marine mammals. This acid was first noticed in 1854 by Hofstädter PG (Ann 1854, 91, 177) in sperm whale oil and named physetoleic acid. Its exact molecular composition (C16H30O2) was proposed in 1906 by Bull H (Ber 1906, 39, 3570) at the time when its actual name was given by Lewkowitsch. Its structure was established in 1925 (Armstrong EF et al., J Soc Chem Ind 1925, 44, 180T). It has been determined to be abundant in the Asclepediaceae Asclepis syriaca seed oil (10%) (Chisholm MJ et al., Can J Chem 1960, 38, 2500), in the Australian Macademia ternifolia seed oil (20%) (Bridge RE et al., J Chem Soc 1950, 2396), and in the Connaraceae Roureopsis obliquifoliata (32%) seed oil (Spencer GF et al., JAOCS 1978, 55, 689). Later, it was  shown to characterized the seeds of all plants of the Proteaceae family (Badami RC et al., Prog Lipid Res 1981, 19, 119). The berry oil of Hippophae rhamnoides (Sea buckthorn) is known to be rich in palmitoleic acid (16-22%). These plants have potential as sustainable feedstocks for producing industrially important octene via metathesis chemistry. 1-Octene is a high-demand feedstock with a global consumption of over half a million tons per year that is primarily used as a comonomer in the expanding production of linear low density polyethylene. Unfortunately, their low yields and poor agronomic properties preclude their commercial use. Metabolic engineering has been done to achieve high levels of n-7 FA accumulation in Arabidopsis (Arabidopsis thaliana) (Nguyen HT et al., Plant Physiol 2010, 154, 1897).Palmitoleic acid was demonstrated to be an adipose tissue-derived hormone (a lipokine) that strongly stimulates in mice muscle insulin action and suppresses hepatosteatosis. Adipose tissue would be able to use lipokines to communicate with distant organs and regulate systemic metabolic homeostasis (Cao H et al., Cell 2008, 134, 933). The amount of palmitoleic acid in serum cholesterol ester reflects the hepatic pool of carbon flux from carbohydrates to fatty acids (Lands W et al., Am J Clin Nutr 1995, 61, 721). Furthermore, as a product of endogenous lipogenesis, palmitoleic acid is reported to correlate with indexes of adiposity and insulin concentrations (Kunesova M et al., Lipids 2002, 37, 27). The present literature seems to suggest that palmitoleic acid is a good marker for excessive carbohydrate consumption, which may reflect a carbohydrate shunt and predict metabolic disease. In fact, an increase in the level of palmitoleic acid around the age of 50 was shown to be associated with an increase in the level of highly sensitive CRP, a marker of inflammation, about twenty years later.
    On the other hand, palmitoleic acid has been used as a biomarker to trace dairy products intake in human (Mozaffarian D et al., Am J Clin Nutr 2013, 97, 854).  
     
  • Petroselinic acid is present as a major component (from 15 to 60%) in many species of Umbelliferae (parsley or coriander oilseeds) and Araliaceae (Hedera helix). Its presence was first noted in 1909 in parsley seed oil (Vongerichten et al., Ber deutsch chem Ges 1909, 42, 1638) and in the seeds of ivy (Hedera) (Steger A et al., Rec Trav Chim 1928, 47, 471) and its exact structure was determined. Within the Umbelliferae, it was shown that the genus Thapsia should be regarded as a useful source of petroselinic acid, which represents an important oleochemical material for the food, cosmetics, chemistry and pharmaceutical industries (Avato P et al., Lipids 2001, 36, 845). Petroselinic acid was also shown to be an important constituent of Geranium sanguineum (Geraniaceae) seed oil (about 48%) (Tsevegsuren N et al., Lipids 2004, 39, 571) and of sweet cicely (Myrrhis odorata, Umbelliferae) (82%). 
  • Vaccenic acid (from Vacca : cow), named also asclepic acid, was discovered in 1928 (Bertram SH, Biochem Z 1928, 197, 433) in animal fats and butter.  
  • Gadoleic acid was first noted in cod liver oil (Bull H, Ber 1906, 39, 3570), present in marine fish, it originates from dietary crustacea. Its structure was given in 1933 (Takano M J, Soc Chem Ind Japon 1933, 36, 1317). A shorter fatty acid of the n-11 family, 16:1 n-11, is abundant in psychrophile bacteria, such as Bacillus (Kaneda T, Biochem Biophys Res Commun 1971, 43, 298) and thermophile bacteria, such as Chthonomonas (Vyssotski M et al., Lipids 2011, 46, 1155). 
  • Nervonic acid, with 24 carbon atoms, was first believed to be characteristic of fats of Elasmobranch fish (first name: selacholeic acid) where it was discovered (Tsujimoto M, J Soc Chem Ind Japon 1927, 30, 868). In the same year, Klenk E (Z physiol Chem 1927, 166, 287) isolated this fatty acid from cerebrosides of brain tissue, and established its structure. This acid is also present in a Cruciferae (Lunaria annua) in high amounts (22-25%) where it can be suitable (together with erucic acid) for production of high-temperature lubricants and engineering nylons.
     
  • Erucic acid, with 22 carbon atoms,  is found in high amounts (up to 50%) in seed oils of the Cruciferae such as Nasturtium, rape, mustard, Lunaria (38-48%) and of the Tropaeolaceae. Other species have been proposed as sources of erucic acid for nonfood applications, crambe (Crambe abyssinica)(about 60%) and meadowfoam (Limnanthes alba) (about 15%) but there has been no sustained production of these plants. This acid is used in the manufacture of polyethylene film. Tests on animals have shown that ingesting oils containing erucic acid over time can lead to a heart condition called myocardial lipidosis. This is temporary and reversible. Other potential effects observed in animals – including changes in the weight of the liver, kidney and skeletal muscle – occur at slightly higher doses. EFSA’s Panel on Contaminants in the Food Chain established a tolerable daily intake of 7 milligrams per kilogram of body weight (mg/kg bw) per day. For most consumers, especially for toddlers (1-2 years old) and other children (3-10), the main contributors to erucic acid exposure in the diet are pastries, cakes and biscuits. For infants (0-12 months), infant formulae is the main source.Erucic acid is not a safety concern for most consumers as average exposure is less than half the safe level. But it may be a long-term health risk for children up to 10 years of age who consume high amounts of foods containing this substance. 

 

N-3 monoenes : An unusual isoform, the lauroleic acid (9-dodecenoic acid, 12:1 n-3) has been described as a natural metabolite of lauric acid (12:0) in rat hepatocytes (Legrand P et al., Lipids 2002, 37, 569)

 

N-5 monoenes : Seeds of Androsace septentrionalis (Primulaceae) were shown to contain an unusual fatty acid : 16:1 n-5 (Tsevegsuren N et al., Lipids 2003, 38, 1173). That fatty acid, together with 18:1 n-5, were describeed in deep-sea Foraminifera (Kharlamenko VI et al., Lipids 2017, 52, 345).

 

N-7 monoenes : The 5-dodecenoic acid (denticetic acid, 12:1 n-7) is present in sperm whale oil. This compound was formerly known to be present in milk lipids. 
The rare 21:4 n-7 has been described in some animal species (crab, sponge, protist), but it was found in high amount (about 9 % of the total fatty acids) in a opisthobranch mollusc, Scaphander lignarius (Vasskog T et al., Mar Drugs 2012, 10, 2676). That fatty acid was shown to be cytotoxic against human cancer cell lines normal lung fibroblasts, more than EPA and arachidonic acid.

 

N-8 monoenes : An isomer (12:1 n-8, linderic acid) has been found as the major fatty acid (47%) in the seed oil of a Lauraceae, Lindera umbellata (Hopkins CY et al., Lipids 1961, 1, 118). This fatty acid is not known to occur in any other plant family.

 

N-10 monoenes : Sapienic acid (16:1 n-10), a 16-carbon fatty acid with a single cis double bond at the sixth carbon from the carboxyl end, is the most abundant fatty acid in human wax sebum, and among hair-bearing animals is restricted to humans (Nicolaides N, Science 1974, 186, 19). Sapienic acid has been also identified in in human hair and nail samples beside 18:1n-10 (Destaillats F et al., J Chromatogr A 2011, 1218, 9384). Thus this fatty acid is truly unique to sebum, hair and nail and is not found anywhere else in the human body.
Notably, this fatty acid has been implicated in the pathogenesis of acne (Downing DT et al., J Am Acad Dermatol 1986, 14, 221) but was shown to be effective against gram-positive bacteria in human skin sebum (Wille JJ et al.., Skin Pharmacol Physiol 2003, 16, 176). Further works characterized its biosynthesis by a Δ-6 desaturase acting on palmitic acid  (Ge L et al., J Invest Dermatol 2003, 120, 707). Sapienic acid has been detected in deep-sea Foraminifera (Kharlamenko VI et al., Lipids 2017, 52, 345).

 

N-12 fatty acids : 16:1 n-12 has been detected in lipid extracts from deep-sea Foraminifera (Kharlamenko VI et al., Lipids 2017, 52, 345).

 

N-14 fatty acids : 21:1 n-14 has been detected in lipid extracts from deep-sea Foraminifera (Kharlamenko VI et al., Lipids 2017, 52, 345).

 

N-15 fatty acids : An unusual 20 carbon fatty acid (20:1 n-15) is found in high concentration (about 60%) in seeds of Limnanthes alba (meadowfoam), an herbaceous winter annual plant native to the pacific Northwest area of the United States. 



No fatty acid exists naturally with the double bond close to the terminal methyl group, only one is chemically synthesized from ricinoleic acid, the undecylenic acid (11:1 n-10).

 

rule1.gif (1033 octets)

 

TRANS-MONOENOIC FATTY ACIDS

 


One geometrical and several positional isomers of oleic acid exist with a trans double bond. Among the naturally occurring  trans isomers, the double bond is in the (n-13), (n-12), (n-9) or (n-7) position.
Vegetable oils and fats are almost trans free, if not warmed at high temperature in the presence of active components. In contrast, trans fatty acids occur in most animal fats especially in butter and ruminant fats. 

 

Among the most common, Elaidic acid (t9-octadecenoic acid) and t-Vaccenic acid (t11-octadecenoic acid) are found in the rumen and in lipids of ruminant animals. trans-Vaccenic acid which is the major trans-monounsaturated fatty acid present in several food products (milk, yoghurt, cheese, butter and meats) results from the bio-hydrogenation of rumenic acid. 

 

The elaidinization reaction was first obtained by a French pharmacist and chemist, Jean-Joseph-Étienne Poutet (1779-1858) (Ann Chim Phys 1819, 12, 58), who observed that trioleine could be converted to the consistency of pork lard when treated with the oxides of nitrogen derived from mercurous nitrate (mainly nitrous acid).

 

 

Later, Boudet F (Ann Chim Phys 1832, 50, 391; J Pharm 1832, 18, 469) studied accurately the reaction and isolated after saponification of “elaidine” (obtained from triolein) a fatty acid melting at 36°C which he named “acide élaidique” (elaïdic acid), from the Greek name of olive (elais, elaidos).

 

 

Until 1952, elaidic acid was known only as a laboratory isomerization product of oleic acid. This trans fatty acid was demonstrated by infrared analysis to be present in substantial quantities in beef fat (Swern D et al., JAOCS 1952, 29, 44). Later, it was shown that trans fatty acids arise in the first stomach of ruminants as products of catalytic hydrogenation of dietary unsaturated fatty acids (conjugated by an isomerase) during bacterial fermentation. As a result, butter, cheese, milk, beef and mutton fats contain approximately 2-8% transfatty acids by weight. 
Trans-fatty acids are also formed in varying amounts during the industrial hydrogenation of plant or fish oils. This hydrogenation improves the thermal stability and prevents any oxidative process in very unsaturated oils. The natural kick found in cis-fatty acids disappears and the molecule becomes linear and thus has physical properties similar to saturated fatty acids as it was observed by Poutet in 1819.

Trans-fatty acids are also formed under the action of thiyl radicals.

 

 

Saturated fatty acids

 

trans-Fatty acid

 

cis-Fatty acid


An unusual trans fatty acid, t3-hexadecenoic acid (trans-16:1 n-13), occurs in eukaryotic photosynthetic membranes (mainly in phosphatidylglycerol) from higher plants and green algae. As this fatty acid is absent from etiolated tissue, it has been inferred that it has a specific role associated with the light reactions of photosynthesis (Gounaris K et al., Biochem J 1986, 237, 313).

 

trans Fatty acids are formed by some bacteria (predominantly gram negative and under anaerobic conditions) via double-bond migration and isomerization.
The predominant 18:1 trans isomers in partially hydrogenated vegetal oils have their double bond in position t9, t10, t11 and t12, but their distribution (10-22% for t8, t9, t10, t11, t12 or t13 isomer) is distinct from that of milk fat, which contains (2-6% of the total fatty acids) vaccenic acid (t11-18:1) as the predominant isomer (about 60% of t11 and 4-8% for each of the others). The trans-18:1 acid contents of beef meat fat and tallow are about 2 % and 5 %, respectively. Its presence in ruminant fats is explained by a biohydrogenation of linoleic acid occurring in the rumen.
The trans isomers account for about 4.5 % of total fatty acids in ewe milk fat and 3 % in goat milk fat. While the contribution of these two milk sources may be estimated as negligible in most EEC countries, in Greece ewe and goat milk fat contribute for about 45 % of the daily consumption of vaccenic acid. 
The daily per capita intake of trans-18:1 acids from ruminant fats was estimated to be about 1.5 g for people from most countries of the EEC, Spain and Portugal being exceptions (about 0.8 g/person/day) (review in Wolff RL, AOCS 1995, 72, 259). An estimation of the trans fatty acid content of foods and intake levels in France has been reported in 2007 (Laloux L et al., Eur J Lipid Sci Technol 2007, 109, 918). The trans fatty acid intakes and their food sources have been determined in the U.S. population (Kris-Etherton PM et al., Lipids 2012, 47, 931).
It is not yet known what effect continuous consumption and exposure to trans fatty acids isomers will have on human health, specifically those present in ruminant fats, deodorized vegetable oils, frying oils, and those present in synthesized products (Aldai N et al., Eur J Lipid Sci technol 2013, 115, 1378). In rats, it was demonstrated that there is a direct retroconversion of dietary trans-vaccenic acid into trans-palmitoleic acid. As it was shown that circulating trans-palmitoleic acid level is associated in man with a lower risk of metabolic syndrome (Kalergis M et al., Front Endocrinol 2013, 4:90), there is a need of deeper knowledge about the origin of that fatty acid and its impact on health.
The relationships between eighteen‑carbon trans fatty acids and inflammation in the context of atherosclerosis has been reviewed (Valenzuela CA et al., Prog Lipid Res 2019, 76, 101009). Briefly, the evidence associating industrial trans fatty acids with cardiovascular diseases risk factors is fairly consistent, in humans there is a clear a relation between these trans fatty acids and higher levels of inflammatory markers. In contrast, studies in humans, animals and in vitro suggest that ruminant (natural) trans fatty acids have null or mildly beneficial effects in cardiovascular health, metabolic parameters and inflammatory markers.
A review focuses on the mechanisms that underlie the deleterious effects of trans fatty acids by comparing the effects of trans fatty acids to those of cis-unsaturated fatty acids and saturated fatty acids (Oteng AB et al., Adv Nutr 2019 Nov 29). This review also carefully explores the argument that ruminant trans fatty acids have differential effects from industrial trans fatty acids. New data on the molecular mechanisms of action of trans fatty acids may lead to new therapeutic ways for the treatment of diseases characterized by disrupted lipid metabolism. A review has focused on the mechanisms that underlie the deleterious effects of trans fatty acids by juxtaposing effects of trans fatty acids against those of cis-unsaturated fatty acids and saturated fatty acids (Oteng AB et al., Adv Nutr 2020, 11, 697). This review also carefully explores the argument that ruminant trans fatty acids have differential effects from industrial trans fatty acids.

Vaccenic acid has been shown to attenuate complications observed in the metabolic syndrome, including dyslipidemia, fatty liver disease, and low-grade inflammation. An explanation of that property could be that vaccenic acid lowers intestinal inflammation by increasing the production of anandamide and related N-acylethanolamines (Jacome-Sosa M et al., J Lipid Res 2016, 57, 638).
A review of the diversity of adverse health effects of individual trans fatty acid isomers may be consulted (Gebauer SK et al., Lipids 2007, 42, 787). A review of the possible effects of trans fatty acids on heart health and the recommendations for the UK population has been reported (Denny AR, Nutr Bull 2008, 33, 124).

 

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