Monoacylglycerols (or "monoglycerides") are esters of the trihydric alcohol glycerol in which only one of the hydroxyl groups is esterified with a long-chain fatty acid. They can exist in three stereochemical forms as illustrated. Our web page on triacylglycerols describes the stereospecific numbering system.
Using most chromatographic separation systems, the 1/3-isomers are not distinguished from each other and are termed 'α-monoacylglycerols', while the 2‑isomers are 'β‑monoacylglycerols'. They tend to be minor components only of most plant and animal tissues, and indeed would not be expected to accumulate because their strong detergent properties would have a disruptive effect on membranes.
One particular monoacylglycerol, i.e. 2-arachidonoylglycerol, is of special biological importance as an endocannabinoid and is more appropriately discussed under that heading in this website, but other monoacylglycerols have specific functions in cells. From a technological standpoint, synthetic monoacylglycerols are important as constituents of commercial detergents. Monoolein has become one of the most important lipids in the fields of drug delivery, emulsion stabilization and protein crystallization, where its physical properties as an amphiphile in aqueous emulsions are so distinctive that it has been termed a ‘magic lipid’, but here the biological properties only of monoacylglycerols are discussed.
Formation and function: 2-Monoacylglycerols are a major end product of the intestinal digestion of dietary fats in animals by the enzyme pancreatic lipase. They are taken up directly by the intestinal cells and converted to triacylglycerols via the monoacylglycerol pathway before being transported in lymph to the liver (see our web pages on triacylglycerols for further details). Within tissues, monoacylglycerols are produced by lipolysis, as has been studied especially in relation to triacylglycerols in adipose tissue. Although it is known that 2-monoacylglycerols can spontaneously isomerize to the 1/3-isomers, which are thermodynamically more stable, the precise conditions under which this occurs in vivo are not clear.
Monoacylglycerols are also produced in bacteria, fungi, plants and animals from diacylglycerols, but not from triacylglycerols, by the action of diacylglycerol lipases. 1,2-Diacyl-sn-glycerols released by the action of phospholipase C on membrane phospholipids in brain and nervous tissue are used to generate 2-arachidonoylglycerol especially by this means. In plants such as Arabidopsis, 2-monoacyl-sn-glycerols are generated for cutin synthesis via an intermediate 2-lysophosphatidic acid produced by specific glycerol-3-phosphate acyltransferases (GPATs). While the bacterial diacylglycerol lipases can also hydrolyse diacylglycerols to glycerol and free fatty acids via monoacylglycerol intermediates, the mammalian enzyme has little monoacylglycerol lipase activity.
It is now recognized that 2-monoacylglycerols and 2-oleoylglycerol in particular have a signalling function in the intestines by activating a specific G-protein coupled receptor GPR119, sometimes termed the ‘fat sensor’, which is believed to be the only receptor responsible for fat-induced release of the gut hormones glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY) and neurotensin. When stimulated, this causes a reduction in food intake and body weight gain in rats and regulates glucose-stimulated insulin secretion. The receptor was at first thought to be located at the apical membrane facing the intestinal lumen, but recent evidence suggests that it my be located at the basolateral membrane. Oleoylethanolamide and 1-oleoyl-lysophosphatidylcholine act in the same manner, but 2‑oleoylglycerol is the most abundant of the potential agonists. Whether these 2-monoacylglycerols have signalling functions in other tissues has yet to be determined. Glycerol monolaurate in human milk is reported to have antimicrobial and anti-inflammatory activity. In the fruit fly Drosophila melanogaster, 2-linoleoyl-glycerol has signalling activities akin to the endocannabinoids.
1-Monoacylglycerol species containing long-chain saturated fatty acids bind to the C1-domain of a protein Munc13-1, which interacts with SNARE proteins to facilitate the priming of insulin granules and consequently to stimulate insulin secretion in pancreatic β-cells. In addition, 1-monoacylglycerol are believe to play an important role in brown adipose activation and energy expenditure by activating PPARα and PPARγ. Acylglycerol kinases that can phosphorylate both 1- and 2‑monoacyl-sn-glycerols to form the important signalling molecule lysophosphatidic acid have been described from brain and other tissues.
Catabolism: In animal cells, monoacylglycerols are catabolized mainly by the action of a monoacylglycerol lipase with formation of free fatty acids and glycerol, although a ubiquitously expressed serine hydrolase α/β-hydrolase domain 6 (ABHD6) is believed to be especially important in regulating the signalling activities of monoacylglycerols. The monoacylglycerol lipase is currently of considerable biological interest as it is highly expressed in aggressive human cancer cells and primary tumours. It appears that the resulting high lipolytic activity increases free fatty acid levels in cancer cells, and these feed into a diverse network of pro-tumorigenic signalling lipids, which promote migration, survival and tumour growth in vivo supporting malignancy. In consequence, a considerable effort is going into development of specific inhibitors of the enzyme. Inhibition of monoacylglycerol lipase is also of potential benefit to a number of other disease states, and for example inhibition of the hydrolysis of 2-arachidonoylglycerol may reduce the release of arachidonic acid for synthesis of pro-inflammatory prostaglandins.
Analysis: During extraction of tissues for analysis, monoacylglycerols undergo acyl migration very rapidly to form a mixture that contains more than 80% of the 1/3‑form. They can be stabilized and purified by chromatography on adsorbents impregnated with boric acid, provided that great care is taken to avoid polar solvents and elevated temperatures. By following appropriate derivatization procedures, stereoisomers monoacylglycerols can be resolved by chiral chromatography (see our webpage on stereospecific analysis of triacyl-sn-glycerols), but it is more usual to analyse them as a total monoacylglycerol fraction isolated by TLC, for example by gas chromatography of the methyl ester derivatives of the fatty acid components.
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|Credits/disclaimer||Updated: May 17th, 2021||Author: William W. Christie|