MONOACYLGLYCEROLS

These lipids (known also as monoglycerides) are fatty acid monoesters of glycerol and thus, due to the orientation of that molecule, two isomeric forms exist:

R is a saturated or an unsaturated hydrocarbon chain. The external carbons are frequently named a and the central one b.
Some monoglycerides are monoesters of terpenic or phenolic acids, in animals or vegetals, respectively.


Monoacylglycerols are found in very low amounts in cell extracts but are intermediates in the degradation of triacylglycerols or diacylglycerols (lipolysis). When diacylglycerols are hydrolyzed by lingual and pancreatic lipases, sn-2-monoacylglycerols are formed but an important proportion is isomerized in the duodenum in sn-1 and sn-3-monoacylglycerols which again can be hydrolyzed (the sn-2 position is lipase resistant). This physiological mechanism is based on the acyl migration from the sn-2 position to the sn-1 or 3 position, migration which is also commonly observed experimentally during purification and in acidic medium. The use of borate ions, added in solvents or on silica gel plates, tends to prevent such artefact.

Some monoacylglycerols may have precise biological properties. Thus, it was demonstrated that a specific monoacylglycerol molecular species, 2-arachidonoylglycerol, is an endogenous ligand for cannabinoid receptors (CB1 and CB2) in brain tissue (Sugiura T et al., Biochem Biophys Res Comm 1995, 215, 89) and in gut (Mechoulam R et al., Biochem Pharmacol 1995, 50, 83). 

Previously believed to be simply an intermediate in tri- and diglyceride metabolism or an alternative source of arachidonic acid, 2-arachidonoylglycerol has lately attracted renewed interest from lipid biochemists and pharmacologists. This is due to the finding of its cannabimimetic activity. The amount of this species was recently shown to be about 5 nmol/g tissue, this being about half of the total monoacylglycerols in the nervous tissue (Kondo S et al., FEBS Letters 1998, 429, 152).  A complete review on this lipid is found in the web site of Biochimica (Moscow) and in review papers (Di Marzo V et al., Lipids 1999, 34 supl, S319; (Howlett AC, Prost Lipid Med 2002, 68-69, 619). Its metabolism has been reviewed by Bisogno T et al. (Bisogno T et al., Pharmacol Biochem Behav 2005, 81, 224). Briefly, the most likely biosynthetic pathway of 2-arachidonoylglycerol involves the hydrolysis of phosphatidylinositol (4,5)-bisphosphate by phospholipase C which generates 1,2-diacylglycerol, which is hydrolyzed to 2-arachidonoylglycerol by diacylglycerol lipase. 
An overview of the biochemistry and pharmacology of 2-arachidonoylglycerol has been released (Hansen HS et al., Eur J Lipid Sci Technol 2006, 108, 877).
Because of their low abundance in living tissues, quantification of 2-arachidonoylglycerol presents numerous technical challenges. A purification using a C18 solid-phase column and a GC/MS analysis permit precise and reproducible quantification in tissue samples (Hardison S et al., Prost Lipid Mediat 2006, 81, 106).
Other fatty acid substitutes, 2-palmitoylglycerol, 2-linoleoylglycerol, 1(3)-palmitoylglycerol and 1(3)-stearoylglycerol fail to bind to CB1 or CB2 receptors with reasonable affinity or mimic 2-arachidonoylglycerol’s biological effects.
Among the various acyl glycerol analogues, an ether-linked analog of 2-arachidonoylglycerol (2-arachidonoyl glyceryl ether or noladin) was described. Noladin was identified in relatively high amounts in dissected thalamus.

Another monoacylglycerol species (2-sciadonoylglycerol) with cannabimimetic activity has been found in seeds of a higher plant (Umbrella pine, Sciadopitys verticillata). This molecule contains a rare unsaturated fatty acid, 5,11,14-eicosatrienoic acid (or sciadonic acid)  (Nakane S et al., Biol Pharm Bull 2000, 23, 758). Its role in the vegetal has not been determined. Another species, 1-butyrylglycerol, is produced during adipocyte differentiation and seems to be a key regulatory molecule in angiogenesis (Dobson DE et al. Cell 1990, 61, 223).    

Monoacylglycerol were shown to be important in the constitution of cutin polymer (Graca J et al., Phytochemistry 2002, 61, 205). Cutin is the structural component of the plant cuticle, the outermost layer of aerial organs of higher plants. Waxes embedded in the cutin make the cuticle an efficient barrier against desiccation and gas exchange and pathogen attack. Cutin polyester is typically composed of esterified hydroxy-fatty acids with 16, 18 and 22 carbon-chains and one terminal hydroxyl (w-position) and other hydroxyl groups in secondary positions. The cutin polymer has been found to be based on the inter-esterification of hydroxyacids (head-to-tail in a linear form or cross-linked) and of glycerol esterified with various hydroxy-fatty acids. Similar structures were described for suberin which is a lipidic polyester present in tree barks, tuber skins and abscisic tissue of falling leaves. It is also formed in plant after wounding. Upon depolymerization, cork suberin releases a mixture of monomers and oligomers, including monoacylglycerols of monoacid (C22), of w-hydroxyacids (C16, 18:1, 22, 24), and of a,w-diacids (C16, 18, 18:1, 22) (Graça J et al., Chem Phys Lipids 2006, 144, 96). Glycerol is a major compound of this polyester, constituting up to 20% by weight of suberin in oak, cotton and potato (Graça J et al., Agric Food Chem 2000, 48, 5476). The current model describes
A monoglyceride containing 26-hydroxy-26:0 fatty acid has been isolated from the root bark of Pentaclethra eetveldeana, used in Zairian traditional medicine for the treatment of hemorrhoids, malaria and epilepsy (Byla B et al., Phytochemistry, 1996, 42, 501). 

Monoacylglycerols are the most polar components of simple lipids (they have only one hydrocarbon chain and 2 alcohol groups) and, thus, need care to prevent their loss in hydrophilic solutions and on chromatographic columns. Furthermore, they have detergent properties, hence they easily form micelles in water solutions.

Monoacylglycerols with saturated or unsaturated fatty acids are by far the most commonly used food surfactants. Surfactants are used in the food industry to prepare food products and increase their shelf life. They give to emulsions their stability and the required viscosity. The first use of monoacylglycerols on an industrial scale was, more than 50 years ago, for making margarine where they emulsify the water phase in oil and fat phase. They are now currently included in low-calorie spreads, peanut butter, ice cream to control their texture, starch-base food (macaroni, noodles, potato products...) and baking industry.
Monoacylglycerols are used also as raw materials for making more lipophilic or more hydrophilic molecules utilized in cosmetics and food industry. Esters are made with acetic, lactic, succinic and citric acids to emulsify commercial products.

  These food additives are permitted for use in foods after they have been tested in toxicological studies and are assigned an E number by a EEC Council Directive or a GRAS number after regulation by the US Food and Drug Administration. Thus, monoacylglycerols, their acetic, lactic and citric esters are labeled as E471, E472a, E472b, and E472c, respectively. In the US, only monoacylglycerols are generally recognized as safe. No established acceptable daily intakes are defined for these surfactants.
Acetic acid esters of monoglyceride, called acetylated monoglyceride, can improve the quality of fats, for example, margarine and are available as a solvent, lubricant, plasticizer for vinylacetate, etc. Although they have no function as emulsifiers, they are usable for foaming fats and oils by themselves or in combination with other emulsifiers.
Lactic acid esters of monoglyceride, called lactylated monoglyceride, are used in shortening for cakes, desserts and foaming for cream by themselves or in combination with monoglycerides.
Succinic Acid esters of monoglyceride, called succinylated monoglyceride, form a complex with starch which is able to react with protein. They are used as dough modifying agents and emulsifiers for shortening.
Citric acid esters of monoglyceride, called citrated monoglyceride, are highly hydrophilic emulsifiers and are  used for margarine, dairy products such as, coffee whitener and cream. They are also used as emulsion stabilizer for mayonnaise and dressing.

Sulfated derivatives of monoglycerides from coconut oil (cocomonoglyceride sulfate - CMGS) have been known for a long time in cosmetic industry. To day CMGS are obtained directly from coconut oil in a solvent-free two-stage process. In the first stage coco-monoglycerides are obtained by simple transesterification of coconut oil with glycerol. This raw material is converted to CMGS by reaction with sulfur trioxide gas. The product is then neutralized with aqueous sodium hydroxide. Because of its technical application properties CMGS is predestined for use in cosmetic products such as shower gels and foam baths or shampoos. In these products, they are used in combinations of alkyl polyglycosides (Behler A et al. Fett/Lipid 1998, 98, 309).

Several terpenoic monoacylglycerols have been isolated from the mollusk nudibranch Archidoris odhneri (Andersen RJ et al., Tetrahedron Lett 1980, 21, 797). The acylated group was a sesquiterpene, farnesic acid.

Farnesic acid monoglyceride

In another nudibranch, Archidoris montereyensis, the acylated group is a diterpenoic acid (Gustafson K et al., Tetrahedron Lett 1984, 25, 11).

Diterpenoic acid monoglyceride

In the same mollusk species, another monoglyceride with a sesquiterpenoic acid of the drimane type was isolated. All these compounds may be a part of the cutaneous chemical used as antifeedants by these animals.

In vegetals, phenolic monoacylglycerols have been isolated. Thus, p-coumaroyl monoglycerides have been described in the medullae of Juncus effusus (Dong-Zhe J et al., Phytochemistry 1996, 41, 545). This plant material is used as a traditional medicine in the Chinese pharmacopoeia. The coumaroyl group was determined to be acylated in sn-1 or in sn-2 position.

2-O-p-Coumaroyl monoglyceride

MONOALKYL ETHERS

The major monoalkyl ethers are: 1-O-hexadecylglycerol (16:0 alkyl or chimyl alcohol), 1-O-octadecylglycerol (18:0 alkyl or batyl alcohol) and 1-O-octadec-9-enyl glycerol (18:1 alk-9-enyl or selachyl alcohol).  The trivial names are based on the fish species from which they have originally isolated. These components are found free in small quantities in various marine oils but are most frequently found either as alkyl-diacylglycerols (similar to triacylglycerols) in elasmobranch fish or as constituents of particular phospholipids in all kinds of cell membranes.
In a few liver oils of elasmobranch these ether lipids form a relatively large proportion of the total unsaponifiable matter (about 10 per cent in Squalus acanthias, 37 per cent in Chimoera monstrosa  and 50-80 per cent in Centrophorus sp or Scymnorhinus sp).

The first evidence of the existence of these lipids seems to have been reported by Dorée C (1909) in England and Kossel A et al. (1915) in Germany. They isolated an unsaponifiable fraction of lipids from starfish they named "astrol", which appeared later to be batyl alcohol and the occurrence of three similar alcohols was demonstrated in 1922 (Tsujimoto M et al., Chem Umschau 1922, 29, 27; 1924, 31, 13). The complete proof of their chemical structure was provided in England by Davies WH et al (1933). Later, it was demonstrated that these compounds are present in the form of fatty acid esters, each of the free hydroxyl groups being combined with a higher fatty acid (André E et al., Compt Rend 1932, 195, 627).

Among the various acyl glycerol analogues, 2-arachidonoyl glyceryl ether, a monoalkyl ether analog of 2-arachidonoylglycerol was first used as a tool to explore in vivo the biological activities of 2-arachidonoylglycerol (Sugiura T et al., J Biol Chem 1999, 274, 2794). This ether lipid, which is resistant to lipases, was later reported to be present in pig brain and to be a specific CB1 agonist. It was named noladin ether (Hanus L et al., PNAS 2001, 98, 3662).

Noladin ether has much greater selective for CB1 over CB2 receptors; however, its activity as a CB1 agonist may be less than that exhibited by 2-arachidonoylglycerol.