Monoglyceride lipase: Difference between revisions

<StructureSection load='' size='450' side='right' scene='58/580298/Overall_structure/2' caption='Secondary structure of MGL'>

2-AG activates the same cannabinoid receptors (CB1 and CB2) for both [http://en.wikipedia.org/wiki/Anandamide anandamide] and the main psychoactive compound found in Cannabis sativa, [http://en.wikipedia.org/wiki/Tetrahydrocannabinol Δ9-Tetrahydrocannabinol] (THC), via [http://en.wikipedia.org/wiki/Retrograde_signaling retrograde signaling]. <ref name="bert" /><ref name="labar" /> In the brain, endocannabinoids (ECs) are released from postsynaptic neurons, causing the retrograde suppression of synaptic transmission. <ref name="Taschler"/> In peripheral tissues,  endocannabinoids (ECs) are active in autonomic nervous system.  EC signalling affects processes such as learning, motor control, cognition, and pain <ref name="Taschler" />. EC signalling is also able to regulate lipid metabolism and food intake. 2-AG is the most abundant endocannabinoid found in the brain, possessing analgesic, anti-inflammatory, immunomodulating, neuroprotective, and hypotensive effects.<ref name="labar" /><ref name="nomura" />  MGL degrades 2-AG, preventing 2-AG from remaining bound to the cannabinoid receptor and therefore terminating the pain signal.  Without the degradation of 2-AG by MGL, 2-AG levels would increase which would lead to a prolonged nociceptive effect <ref name="Clemente" />

Approximately 85% of the 2-AG in the rat brain is metabolized by MGL, while other lipases such as [http://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase fatty acid amide hydrolase] (FAAH) process the remainder of the metabolite.<ref name="blank" /> Based on these studies, MGL has been assigned as the primary enzyme for the metabolism of 2-AG in humans, making it a highly desirable target enzyme for the modulation of 2-AG concentration in the body. <ref name="labar" /><ref name="bert" /><ref name="shalk" /> A deficiency in MGL in animals led to the buildup of 2-AG <ref name="Taschler" />.  The endocannabinoid 2-AG has a nociceptive effect in pain signalling <ref name="Clemente" />. Although the most-studied role of MGL is the degradation of 2-AG in the brain, MGL may also play a role in adipose tissue, completing the hydrolysis of triglycerides into fatty acids and glycerol, as well as working in the liver to mobilize triglycerides for secretion. <ref name="labar" /><ref name="shalk" />