Pharmacological characterization of human monoglyceride lipase cystein mutants

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Julie Kařízková Supervisors: Docent Jarmo T. Laitinen, Ph.D., Juha R. Savinainen, Ph.D., PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Pharmacological characterization of human monoglyceride lipase cystein mutants The therapeutic and psychotropic potential of Cannabis Sativa has been known for ages but the biochemical basis of physiological processes behind the scene was only recently revealed. The most psychotropic constituent of the plant, tetrahydrocannabinol (Δ 9 -THC), hits the function of the endocannabinoid system which includes the endocannabinoids, metabolic enzymes for the biosynthesis and degradation, and cannabinoid receptors which all were discovered and described quite recently. Through the past 20 years, more and more chemical compounds are being classified or at least studied as the endogenous ligands of the cannabinoid receptors, although the two most famous, explored and plentiful compounds are anandamide (AEA) and the primary endocannabinoid 2-arachidonoylglycerol (2-AG). The most frequent manner of 2-AG-degradation is enzymatic hydrolysis by monoglyceride lipase (MGL) and α/β-hydrolase domain-containing proteins ABHD6 and ABHD12. MGL has several critical..