AMP-activated protein kinase system

At the molecular level, precise target recep-tor(U)ave not been identified. Metformin has been reported to activate the AMP-activated protein kinase system (AMPK) in primary hepatocytes (131). AMPK has been proposed as a key regulatory enzyme of carbohydrate and fat metabolism (132). This kinase is activated through an allosteric mechanism by binding 5 -AMP and also by phosphorylation. Activation of AMPK by phosphorylation is 5 -AMP dependent because the binding of AMP to the enzyme makes it a better substrate for AMPK kinase, which phosphorylates AMPK, and a poorer substrate for protein phosphatase 2C, which dephosphorylates it. AMPK kinase is also activated by 5 -AMP. These actions of 5 -AMP are antagonized by high concentrations of ATP, and thus the system... 

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