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

Vandevoorde, Séverine; Saha, Bijali; Mahadevan, Anu; Razdan, Raj K.; Pertwee, Roger G.; Martin, Billy R.; Fowler, Christopher J.

doi:10.1016/j.bbrc.2005.09.015

Cited by 47 publications

(46 citation statements)

References 37 publications

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“…5). The reversal of cardanol's sensitizing effect on neuronal cell death by NAE 16:0 begins well below its reported IC 50 of 5.1 M for anandamide hydrolysis by rat brain FAAH (44,45), which may indicate that cardanol-EA does not affect binding of NAE 16:0 to rat FAAH in the same way that it does with anandamide (3.1-fold increase in K m ; Fig. 6).…”

Section: Discussionmentioning

confidence: 67%

Synthesis of Phenoxyacyl-Ethanolamides and Their Effects on Fatty Acid Amide Hydrolase Activity

Faure

Nagarajan

Hwang

et al. 2014

Journal of Biological Chemistry

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Background: Fatty acid amide hydrolase (FAAH) belongs to the family of amidase signature proteins and is involved in N-acylethanolamine (NAE) metabolism. Results: New synthetic phenoxyacyl-ethanolamide compounds increased the amidohydrolase activity of FAAH. Conclusion: Phenoxyacyl-ethanolamide compounds increased the activity of the FAAH enzyme in plants and animals. Significance: New properties of FAAH proteins were revealed with these phenoxyacyl-ethanolamide compounds, and the potential for their applications in vivo was demonstrated.

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Section: Discussionmentioning

confidence: 67%

Synthesis of Phenoxyacyl-Ethanolamides and Their Effects on Fatty Acid Amide Hydrolase Activity

Faure

Nagarajan

Hwang

et al. 2014

Journal of Biological Chemistry

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“…MGL is expressed in many other tissues as well, including brain, liver, skeletal muscle, adipose, and intestine ( 10-13 ). Within cells, MGL localizes to both the cytosolic and membrane fractions and hydrolyzes sn -1 and sn -2 MGs of varying acyl chain lengths and degrees of unsaturation, with almost no activity toward other lipids, such as TG and lyso-phospholipids ( 10,(14)(15)(16)(17)(18).MGL is involved in energy balance through two important functions. Abbreviations: AA, arachidonic acid; AEA, arachidonoyl ethanolamide; 2-AG, 2-arachidonoyl glycerol; AUC, area under the curve; CB, cannabinoid; EC, endocannabinoid; HFD, high-fat diet; HOMA-IR, homeostatic model assessment of insulin resistance; iMGL, mice that overexpress monoacylglycerol lipase specifi cally in the intestinal mucosa; LFD, low-fat diet; MG, monoacylglycerol; MGL, monoacylglycerol lipase; OFTT, oral fat tolerance test; OGTT, oral glucose tolerance test; RER, respiratory exchange ratio .…”

mentioning

confidence: 99%

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confidence: 99%

Global deletion of MGL in mice delays lipid absorption and alters energy homeostasis and diet-induced obesity

Douglass

Zhou

et al. 2015

Journal of Lipid Research

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energy storage, membrane components, and signaling. Extracellular hydrolysis of dietary TG in circulating lipoproteins yields FFAs and sn -2 MG, which are then taken up by cells ( 1,2 ). MGs are also produced intracellularly from membrane phospholipids and the consecutive action of phospholipase C and diacylglycerol lipase, or from the hydrolysis of stored TG by adipose TG lipase (ATGL) and hormone sensitive lipase (HSL) ( 2-5 ). The ultimate fate of intracellular MGs is hydrolysis to FFAs and glycerol or reesterifi cation by acyltransferases into diacylglycerol and TG ( 6, 7 ).MG lipase (MGL) is considered the rate-determining enzyme in MG catabolism. MGL accounts for roughly 85% of MG hydrolysis in the brain, with the remainder being catalyzed by the enzymes ABHD6 and ABHD12 ( 8,9 ). MGL is expressed in many other tissues as well, including brain, liver, skeletal muscle, adipose, and intestine ( 10-13 ). Within cells, MGL localizes to both the cytosolic and membrane fractions and hydrolyzes sn -1 and sn -2 MGs of varying acyl chain lengths and degrees of unsaturation, with almost no activity toward other lipids, such as TG and lyso-phospholipids ( 10,(14)(15)(16)(17)(18).MGL is involved in energy balance through two important functions. Abbreviations: AA, arachidonic acid; AEA, arachidonoyl ethanolamide; 2-AG, 2-arachidonoyl glycerol; AUC, area under the curve; CB, cannabinoid; EC, endocannabinoid; HFD, high-fat diet; HOMA-IR, homeostatic model assessment of insulin resistance; iMGL, mice that overexpress monoacylglycerol lipase specifi cally in the intestinal mucosa; LFD, low-fat diet; MG, monoacylglycerol; MGL, monoacylglycerol lipase; OFTT, oral fat tolerance test; OGTT, oral glucose tolerance test; RER, respiratory exchange ratio .

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“…For cell-free preparations, MAGL and FAAH were assayed as described previously (see Vandevoorde et al, 2005), although for the experiments run in Sweden a different extraction protocol (Boldrup et al, 2004) was used for the three highest concentrations of URB602 and for FAAH; data shown as an inset to Figure 1a. For intact cells, a modification of the assay described by Jonsson et al (2001) was used.…”

Section: Assay Of Magl and Faahmentioning

confidence: 99%

“…Methanol (400 ml) was added and the cells were collected by scraping the wells. Aliquots (400 ml) were transferred to glass tubes, chloroform (200 ml) was added, and the assays completed as described for the cell-free preparations (Vandevoorde et al, 2005). Results are expressed as percentage of controls treated with the same concentration of vehicle.…”

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confidence: 99%

Lack of selectivity of URB602 for 2‐oleoylglycerol compared to anandamide hydrolysis in vitro

Vandevoorde

Jonsson

Labar

et al. 2007

British J Pharmacology

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Background and purpose: Two compounds, URB602 and URB754, have been reported in the literature to be selective inhibitors of monoacylglycerol lipase, although a recent study has questioned their ability to prevent 2-arachidonoyl hydrolysis by brain homogenates and cerebellar membranes. In the present study, the ability of these compounds to inhibit monoacylglycerol lipase and fatty acid amide hydrolase has been reinvestigated. Experimental approach: Homogenates and cell lines were incubated with test compounds and, thereafter, with either3 H]-anandamide. Labelled reaction products were separated from substrate using chloroform: methanol extraction. Key results: In cytosolic fractions from rat brain, URB602 and URB754 inhibited the hydrolysis of 2-oleoylglycerol with IC 50 values of 25 and 48 mM, respectively. Anandamide hydrolysis by brain membranes was not sensitive to URB754, but was inhibited by URB602 (IC 50 value 17 mM). Hydrolysis of 2-oleoylglycerol by human recombinant monoacylglycerol lipase was sensitive to URB602, but not URB754. The lack of selectivity of URB602 for 2-oleoylglycerol compared to anandamide hydrolysis was also observed for intact RBL2H3 basophilic leukaemia cells. C6 glioma expressed mRNA for monoacylglycerol lipase, and hydrolyzed 2-oleoylglycerol in a manner sensitive to inhibition by methyl arachidonoyl fluorophosphonate but not URB754 or URB597. MC3T3-E1 mouse osteoblastic cells, which did not express mRNA for monoacylglycerol lipase, hydrolyzed 2-oleoylglycerol in the presence of URB597, but the hydrolysis was less sensitive to methyl arachidonoyl fluorophosphonate than for C6 cells. Conclusions and implications:The data demonstrate that the compounds URB602 and URB754 do not behave as selective and/or potent inhibitors of monoacylglycerol lipase.

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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

Cited by 47 publications

References 37 publications

Synthesis of Phenoxyacyl-Ethanolamides and Their Effects on Fatty Acid Amide Hydrolase Activity

Synthesis of Phenoxyacyl-Ethanolamides and Their Effects on Fatty Acid Amide Hydrolase Activity

Global deletion of MGL in mice delays lipid absorption and alters energy homeostasis and diet-induced obesity

Lack of selectivity of URB602 for 2‐oleoylglycerol compared to anandamide hydrolysis in vitro

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