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anandamide degradation

Anandamide, a member of the endocannabinoid class of signaling lipids, is the amide of ethanolamine and arachidonate. It is part of the endocannabinoid system, a neural signaling pathway consisting of endogenous cannabinoids (endocannabinoids), cannabinoid receptors, and the enzymes that biosynthesize and degrade endocannabinoids. Studies suggest that the function of the endocannabinoid system is related to pain modulation, the immune system, neuroprotection, and addiction. Models have been proposed for endocannabinoid regulation of endogenous reward mechanisms in the brain. Anandamide is biosynthesized in the membrane from the phospholipid precursor N-arachidonoylphosphatidylethanolamine. Calcium activated phospholipase D releases it into the synapse. Anandamide is thought to interact with the G-protein coupled CB1 cannabinoid receptor in the central nervous system. Activation of CB1 receptors by enodcannabinoids (or by exogenous cannabinoids) suppresses neurotransmission. Its action at the CB1 receptor is terminated by a comnbination of transport (by an as yet unidentified mechanism), followed by hydrolysis by fatty acid amino hydrolase (FAAH). This enzyme has been studied as a potential therapeutic target and inhibitors of its activity have been developed. FAAH knockout mice have been produced that show CB1-dependent behavioral responses . A single nucleotide polymorphism in the human gene encoding FAAH has been found to be strongly associated with drug and alcohol abuse . This polymorphism results in an enzyme with increased sensitivity to proteolysis. The arachidonate product of the enzyme can be oxidized as shown by the pathway link, or it can be converted to biologically active eicosanoids (prostaglandins, prostacyclins, thromboxanes, leukotrienes, and lipoxins). Ethanolamine can be used in the biosynthesis of phosphatidylethanolamine, as shown by the pathway link. In and reviewed in .

from BIOCYC source record: HUMAN_PWY6666-1
Type: pathway
Taxonomic scope
organism-specific biosystem
Homo sapiens

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