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MAGL

MAGL is an enzyme that belongs to the serine hydrolase family. It participates in lipid metabolism and in the regulation of the ECS. This enzyme preferentially catalyzes the hydrolysis of monoglycerides (versus di- or triglycerides) into glycerol and fatty acids and specifically degrades the endocannabinoid 2-AG, turning into the main enzyme responsible for the control and regulation of the levels of this endocannabinoid. This catalytic activity has led to a huge interest in its structural characterization, its function, and in the development of new compounds able to regulate its activity. They consisted of 303 amino acids with a molecular weight of 33.4 kDa. A high sequence similarity was observed among the three enzymes: 92% identity between rat and mouse and 83.8 and 84.2%, respectively, for mouse and rat with human MAGL. The catalytic site is formed by the triad Ser-Asp-His commonly found in the serine hydrolase family, which in the human MAGL is constituted by Ser122, Asp239, and His269. In cancer cells, MAGL hydrolyses monoacylglycerols into free fatty acids maintaining tonically elevated levels of these molecules, which are further converted into different pro-tumorigenic lipids such as lysophospatidic acid (LPA), PGE2, lysophosphatidyl choline, lyosphosphatidyl ethanolamine or monoalkylglycerol ether.

References

1.Gil-Ordó?ez A,et al. Biochem Pharmacol. 2018;157:18–32.

Metabolic Enzyme/Protease

11β-HSD(15) 15-PGDH(1) ACC(10) ACE(9) AChE(29) Adenylate Cyclase(10) ALDH(14) Aldose Reductase(5) Aminopeptidase(17) BACE(18) Casein Kinase(41) CAT(5) Cathepsin(8) CETP(10) COMT(2) CPG2(1) CYPs(6) Decarboxylase(3) Dehydrogenase(87) DGAT(4) Dopamine beta-hydroxylase(2) DPP(28) Elastase(6) FAAH(19) Factor Xa(22) Fatty Acid Synthase(16) Ftase(2) FXR(22) Glucokinase(1) GSNOR(2) Guanylate Cyclase(9) HMGCR(17) IDH(7) IDO(20) IMPDH(2) LDH(2) LDL(5) Lipase(13) Lipid(9) Lipoxygenase(0) MAGL(3) MAO(51) MMP(48) NAMPT(7) Neprilysin(6) NKCC(0) Other Targets(8) P450(87) PAI-1(7) Phosphatase(49) Phospholipase(42) PPAR(86) Protein Phosphatase/PTP(6) Renin(7) Retinoid Receptor(23) SCD(6) Steroid Sulfatase (STS)(2) Thioredoxin(1) TPH(5) Transferase(24) Vitamin(39) Xanthine Oxidase (XAO)(6)