Monoacylglycerol hydrolase

Anandamide amidase recognizes and hydrolyzes 2-AG (Goparaju, 1999 Di Marzo, 1999 Lang, 1999) however, there is evidence for the existence of another specific hydrolase [monoacylglycerol (MAG) lipase] that hydrolyzes 2-AG (D. Piomelli and A. Makriyannis, 2000, personal communication). In addition to this pathway, 2-AG diffuses rapidly into the cell membrane where it could be either hydrolyzed to arachidonic acid and glycerol or esterified back to phosphoglycerides (Di Marzo, 1999b). 

R. Mentlein, H. Rix-Matzen, E. Heymann, Subcellular Localization of Nonspecific Carboxylesterases, Acylcarnitine Hydrolase, Monoacylglycerol Lipase and Palmitoyl-CoA Hydrolase in Rat Liver , Biochim. Biophys. Acta 1988, 964, 319-328. 

Abstract Tissue concentrations of the endo cannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are regulated by both synthesis and inactivation. The purpose of this review is to compile available data regarding three inactivation processes fatty acid amide hydrolase, monoacylglycerol lipase, and cellular membrane transport. In particular, we have focused on mechanisms by which these processes are modulated. We describe the in vitro and in vivo effects of inhibitors of these processes as well as available evidence regarding their modulation by other factors. 

Keywords Fatty acid amide hydrolase Monoacylglycerol lipase Transporter Carrier Anandamide 2-Arachidonoylglycerol N-Arachidonoylethanolamine... 

Monoacylglycerol lipase Long-chain acyl-CoA hydrolase... 

Fig. 2. Targeted lipidomics of 2-AG metabolism. Postulated pathways for 2-AG metabolism. Abbreviations PLC, phospholipase C DAG, diacylglycerol DGL, diacylglycerol lipase MGL, monoacylglycerol lipase PLA, phospholipase A AT, acyltransferase TAGL, triacylglycerol lipase PIP2, phosphatidylinositol bisphosphate ABHD-6/12 hydrolase lyso-PL, lysophospholipid lyso-PA, lysophosphatidic acid PA, phosphatidic add P, phosphatase COX, cydooxygen-ase LOX, lipoxygenase CYP450, cytochrome P450 CDP, cytidine diphosphate.

Pancreatic lipase, in the presence of bile salts and coUpase, acts at the oil-water interface of the triglyceride emulsion to produce fatty acids and 2-monoacylglycerols. Cohpase is secreted in pancreatic juice as an inactive proenzyme, which is converted to the active form by trypsin. Other significant enzymes involved in the breakdown of fats within the intestinal lumen are cholesterol ester hydrolase, phospholipase A, and a nonspecific bile salt-activated lipase. 

AA arachidonic acid, 2-AG 2-arachidonoyl glycerol, DHA docosahexaenoic add, FAAH fatty add amide hydrolase, DAGL sn-1-selective diacylglycerol lipase, MAGL monoacylglycerol lipase, NAPE-PLD N-acylphosphatidylethanolamine-selective phospholipase D... 

Ghafouri N, Tiger G, Razdan RK, Mahadevan A, Pertwee RG, Martin BR, Fowler CJ (2004) Inhibition of monoacylglycerol lipase and fatty acid amide hydrolase by analogues of 2-arachidonoylglycerol. Br J Pharmacol 143 774-784... 

Vandevoorde, S., Saha, B., Mahadevan, A., Razdan, R. K., Pertwee, R. G., Martin, B. R. and Fowler, C. J., Influence of the degree of unsaturation of the acyl side chain upon the interaction of analogues of 1-arachidonoylglycerol with monoacylglycerol lipase and fatty acid amide hydrolase, Biochem Biophys Res Commun, 337 (2005) 104-109. 

The source of TG used for assembly with apo B has been proposed to originate primarily (-70%) from the cytosolic TG storage pool rather than from the pool of TG made by de novo synthesis in the ER [10]. One model for the assembly of TG with apo B is that cytosolic TG is hydrolyzed, perhaps by the microsomal TG hydrolase (R. Lehner, 1999), to diacylglycerol/monoacylglycerol, which are subsequently re-esterified in the ER lumen to TG which assembles with apo B. However, many questions remain regarding the topology of this proposed lipolysis/re-esterification cycle and the molecular identity of the players. For example, it is not known if the active site of the enzyme that makes TG for assembly with apo B resides on the lumenal or cytosolic side of the ER membrane. If the formation of TG by re-esterification occurred within the ER lumen, one would also need to explain how fatty acids entered the ER lumen. 

This chapter discusses the current state of description of the genes encoding CBRs, from their serendipitous identification to the existence of an EPCS. This previously unknown but ubiquitous EPCS consists of the membrane cannabinoid receptors, their hgands, endocannabinoids that are known to act as retrograde messengers, and the associated proteins for their biosynthesis, e.g., phospholipase D, and for their inactivation, e.g., fatty add amide hydrolase (FAAH) and monoacylglycerols. 

De Jong, B. J., and Hulsmann, B. C. (1978) Monoacylglycerol Hydrolase Activity of Isolated Rat Small Intestinal Cells, Biochim. Biophys. Acta 27, 36-46. 

True lipases from plants will hydrolyze these partial glycerides, but other enzymes that attack monoacylglycerols (but not triacylglycerols) have been described. However, in most cases the full substrate specificities of these enzymes have not been studied. In one case a lipolytic acyl hydrolase from potato tubers was shown to hydrolyze mono- and diacylglycerols in addition to a range of polar lipids. Thus, to avoid introducing a class of hydrolytic... 

Enzymes that cleave the acyl residues of mono-and digalactosyl-diacylglycerides are localized in green plants. A substrate specificity study for such a hydrolase from potato (Table 3.25) shows that plants also contain enzymes that are able to hydrolyze polar lipids in general. The potato enzyme preferentially cleaves the acyl residue from monoacylglycerols and lysolecithin, whereas triacylglycerols, such as triolein, are not affected. 

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