Sandbox Reserved 919: Difference between revisions
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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]. It is the most abundant endocannabinoid found in the brain, and it is believed to possess analgesic, anti-inflammatory, immunomodulating, neuroprotective, and hypotensive effects, as well as being capable of inhibiting growth of cancer cells in prostate and breast tissue. <ref name="labar" /> <ref name="nomura" /> | 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]. It is the most abundant endocannabinoid found in the brain, and it is believed to possess analgesic, anti-inflammatory, immunomodulating, neuroprotective, and hypotensive effects, as well as being capable of inhibiting growth of cancer cells in prostate and breast tissue. <ref name="labar" /> <ref name="nomura" /> | ||
Studies have shown that around 85% of 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"> PMID:18096503 </ref> This evidence indicates that MGL is the primary enzyme for the metabolism of 2-AG in humans, making it a highly desirable target molecule for the modulation of 2-AG concentration in the body. Most MGL is found in the cell membrane, although it has been discovered in the cytosol as well. <ref name=" | Studies have shown that around 85% of 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"> PMID:18096503 </ref> This evidence indicates that MGL is the primary enzyme for the metabolism of 2-AG in humans, making it a highly desirable target molecule for the modulation of 2-AG concentration in the body. Most MGL is found in the cell membrane, although it has been discovered in the cytosol as well. <ref name="labar" /><ref name="bert" /><ref name="shalk" /> 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" /> | ||
Three general MGL [http://en.wikipedia.org/wiki/Enzyme_inhibitor inhibitor] classes have been observed: noncompetitive, partially irreversible inhibitors such as [http://en.wikipedia.org/wiki/URB602 URB602]; irreversible serine-reactive inhibitors such as [http://en.wikipedia.org/wiki/JZL184 JZL184] and | Three general MGL [http://en.wikipedia.org/wiki/Enzyme_inhibitor inhibitor] classes have been observed: noncompetitive, partially irreversible inhibitors such as [http://en.wikipedia.org/wiki/URB602 URB602]; irreversible serine-reactive inhibitors such as [http://en.wikipedia.org/wiki/JZL184 JZL184] and <scene name='57/573134/Sar629/1'>SAR 629</scene>; and cysteine-reactive inhibitors such as [http://www.chemspider.com/Chemical-Structure.24774833.html N-arachidonoylmaleimide] (NAM). <ref name="bert" /> Despite the existence of such compounds, there is a strong demand for the creation of more highly-specific and more potent inhibitors that could be used as anti-pain drugs for their ability to keep 2-AG active in the neuronal synapses. <ref name="labar" /> | ||
MGL is an enzyme of immense interest for cancer research, with the potential to help distinguish the role of fatty acids in [http://en.wikipedia.org/wiki/Malignancy malignancy], the varying efficacy of endocannabinoids as anti-cancer agents in different body tissues, and the multifarious influences on the PI-3k/Akt signaling pathway in [http://en.wikipedia.org/wiki/Carcinogenesis carcinogenesis]. | MGL is an enzyme of immense interest for cancer research, with the potential to help distinguish the role of fatty acids in [http://en.wikipedia.org/wiki/Malignancy malignancy], the varying efficacy of endocannabinoids as anti-cancer agents in different body tissues, and the multifarious influences on the PI-3k/Akt signaling pathway in [http://en.wikipedia.org/wiki/Carcinogenesis carcinogenesis]. | ||