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NPPA β-AR GNAS Thyrotropin receptor TSH LIPE PLIN1 CIDEC ATGL CGI-58 Adenylate cyclase type 1 PKA Neuropeptide Y receptor type 1 Gi Prostaglandin E2 receptor EP3 subtype Adenosine receptor A1 IRS Akt complex AdPLA PDE3B PP2A LIPE MGLL NPPA NPR1 LIPE Aquaporin-7 Putative aquaporin-7B Insulin receptor Prostaglandin E2 receptor EP3 subtype aFABP aFABP MGLL aFABP COX ATGL CGI-58 CIDEC PLIN1 Adenylyl cyclase complex PRKACA PI3K PRKG1 cGMP cAMP Norepinephrine Epinephrine Corticosterone cAMP Adenosine Prostaglandin E2 Insulin Arachidonic acid Corticosterone Glycerol Glycerol Fatty acid Fatty acid Insulin Prostaglandin E2 Triglyceride Diglyceride Monoglyceride Fatty acid Fatty acid AMP Pi Triglyceride Diglyceride ATP Pi Pi Magnesium Fasted Physical alteration of the lipid droplet surface Fed The FAs and Glycerol generated during lipolysis can be released into the circulation for use by other organs In the fed state, insulin binding to the insulin receptor (IR), results in decreased lipolysis. Insulin also suppresses expression of ATGL. PKA phosphorylates HSL resulting in its translocation from the cytosol to the lipid droplet where it can hydrolyze DAG. PKA phosphorylates the lipid droplet associated protein perilipin to provide lipases greater access to the lipid droplet ATGL initiates lipolysis by hydrolyzing triacylglycerol (TAG) to diacylglycerol (DAG). Hormone-sensitive lipase (HSL) hydrolyzes DAG to monoacylglycerol (MAG), which is subsequently hydrolyzed by MAG lipase to generate glycerol and three fatty acids (FAs). Cytosol Extracellular During the fed state insulin binds to its receptor in adipocytes and initiates a signaling event that, via phosphorylation and activation of phosphodiesterase 3B (PDE3B), decreases cAMP and ultimately inhibits lipolysis Cytosol Extracellular PKA inhibit HSL to decrease lipolysis Lipid Droplet Lipid Droplet