154 V. Marzo et al.
of 2-alkenyl glyceryl ethers from the corresponding fatty acyl alcohols; and (3)
although similar enzymes had been previously identified, these had a stringent
specificity for thesn-1 position of glyceryl ethers with short-medium chain, satu-
rated fatty acids (Nagan and Zoeller 2001). Oka et al. (2003), using MS techniques,
could not confirm the presence of 2-AGE in the brain of several mammalian species
including pig and rat. These contradictory data might be explained by the use of
different extracting procedures, or with the possibility of a “false-positive” MS sig-
nal, i.e. an endogenous compound structurally related but not identical to 2-AGE
(i.e. with the same molecular weight and similar mass spectrometric fragmenta-
tion pattern), which cannot be picked up by all MS techniques. This compound,
however, cannot be the 2-AGE isomer 1-arachidonyl glyceryl ether, which can be
distinguished from 2-AGE simply on the basis of its chromatographic properties.
Clearly, if the existence of 2-AGE were to be confirmed by future studies carried
out in other laboratories using exactly the same procedures used by Hanus et
al. (2001) and Fezza et al. (2002), some as-yet-unknown biosynthetic pathway,
different from that leading to plasmalogens, may exist for this compound. Neurob-
lastoma N18TG2 intact cells are not capable of converting arachidonate-containing
phospholipids into 2-AGE when stimulated with ionomycin, i.e. under conditions
where high levels of 2-AG are produced (Fezza et al. 2002). This might suggest a
Ca2+-independent or a non-phospholipid-mediated pathway for the formation of
this putative endocannabinoid in neurons.
Fig. 3.Major biosynthetic pathways and enzymes for the endocannabinoid 2-arachidonoyl-glycerol (2-AG).
DAG, di-acyl-glycerol lipase;PA, phosphatidic acid;PI, phosphoinositide;PLC, phospholipase C. P represents a
phosphate group