The Lipid Library

MONOACYLGLYCEROLS

STRUCTURE, COMPOSITION, FUNCTION AND ANALYSIS

1.   Monoacylglycerols - as Components of Oils and Fats

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, and they can exist in three stereochemical forms.

Normally 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. Indeed synthetic monoacylglycerols are important as constituents of commercial detergents. 2-Monoacylglycerols are a major end product of the intestinal digestion of dietary fats in animals via 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).

Monoacylglycerols undergo acyl migration very rapidly indeed 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. It is more usual to analyse them as a 'total' monoacylglycerol fraction isolated by TLC by gas chromatography of the methyl ester derivatives of the fatty acid components..

2.  2-Arachidonoylglycerol

2-Arachidonoylglycerol is mainly a product of phosphatidylinositol catabolism, and is important in animal tissues as an endogenous ligand for cannabinoid receptors, i.e. it is an endocannabinoid. It was first detected in brain, where it occurs at levels of nmol/g tissue, but it is now known to be present in many other organs. When isomerized to the 1/3-isomer, it loses its biological potency, and this probably occurs fairly rapidly in vivo, although a monoacylglycerol lipase is also involved in its catabolism. As a neutral lipophilic molecule, it is possible that 2-arachidonoylglycerol can diffuse freely through membranes to reach the sites of activity, since no active transport system has been identified to date.

Like anandamide, 2-arachidonoylglycerol is synthesised upon demand from phospholipid precursors in cell membranes in response to a rise in intra-cellular calcium levels. Biosynthesis may occur by two routes. Diacylglycerols generated from phosphatidylinositol can be hydrolysed by a diacylglycerol lipase to yield 2-arachidonoylglycerol. Alternatively, a specific phospholipase A₁ may act upon phosphatidylcholine to generate 2-arachidonoyl-lysophosphatidylcholine, which is in turn acted upon by a lysophospholipase C to produce 2-arachidonoylglycerol.

Our web pages on anandamide discuss the general topic of the endogenous cannabinoids, although there is evidence to suggest that 2-arachidonoylglycerol is a more important natural ligand for both the CB1 and the CB2 cannabinoid receptors. While anandamide may only act as a partial agonist at these cannabinoid receptors, 2-arachidonoylglycerol usually acts as a full agonist. In addition, it has many activities distinct from those of anandamide. For example, amongst innumerable metabolic functions that have been reported, it is believed to be a messenger molecule that regulates the transmission of signals across synapses, and it is involved as a mediator of inflammatory reactions and immune responses. In brain and nervous tissue, it is believed to suppress the elevation of cyclooxygenase(COX)-2 expression in response to proinflammatory stimuli and may ameliorate neurodegenerative diseases. Recent findings that 2-arachidonoylglycerol has a role in the regulation of the proliferation and invasion of certain types of cancer cells and that it may be relevant to cardiovascular disease will no doubt stimulate much more interest.

2-Arachidonoylglycerol can also function as a precursor of glycerol-linked prostanoids, through a specific and efficientinteraction with the enzyme COX-2 followed by further downstream processing. These may constitute a new class of lipid mediator with distinctive biological properties in their own right.

Within cells, 2-arachidonoylglycerol has a short half-life and is rapidly hydrolysed to arachidonic acid and glycerol by either the fatty acid amide hydrolase (which also acts upon anandamide) or by the monoacylglycerol lipase.

The 2-glycerol ether analogue (termed ‘noladin ether’) has similar biological activity in vitro, and it has been reported to occur naturally in porcine brain.

It has recently been demonstrated that two metabolites of 2-arachidonoyl-glycerol, produced by the action of a cytochrome P450 enzyme, i.e. 2-(11,12-epoxyeicosatrienoyl)-glycerol and 2-(14,15-epoxyeicosatrienoyl)-glycerol, are produced in various animal tissues. They activate both cannabinoid receptors CB1 and CB2 with high affinity and elicit biological responses in cultured cells. They may be new members of the endocannabinoid family.

References

• Christie, W.W. Lipid Analysis - 3rd Edition. (Oily Press, Bridgwater) (2003).
• Kokotos, G. Endocannabinoids. In: Bioactive Lipids. pp. 245-264. (edited by A. Nicolaou and G. Kokotos, The Oily Press, Bridgwater) (2004).
• Sugiura, T., Kishimoto, S., Oka, S. and Gokoh, M. Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. Prog. Lipid Res., 45, 405-446 (2006).

Updated: 5/9/2008 Credits/disclaimer	Scottish Crop Research Institute (and MRS Lipid Analysis Unit), Invergowrie, Dundee (DD2 5DA), Scotland	Right click on the icon to open in a new window