Adenosine 5′-monophosphate-activated protein kinase (AMPK)
Adenosine 5′-monophosphate-activated protein kinase (AMPK) now appears to be a metabolic master switch, phosphorylating key target proteins that control flux through metabolic pathways of hepatic ketogenesis, cholesterol synthesis, lipogenesis, and triglyceride synthesis, adipocyte lipolysis, and skeletal muscle fatty acid oxidation. AMPK is an evolutionarily conserved signaling molecule that is emerging as one of the most important energy sensors in the body. AMPK monitors cellular energy status and is activated via phosphorylation when energy stores are low. This allows for maintenance of energy homeostasis by promoting catabolic pathways for ATP production and limiting processes that consume ATP. Growing number of stimuli have been shown to activate AMPK, and AMPK has been implicated in many diverse biological processes, including cell polarity, autophagy, and senescence.
Adenosine monophosphate-activated protein kinase is involved in the insulin-sensitizing action of adipocyte hormones, adiponectin and leptin and antidiabetic drugs. One important novelty is that adenosine monophosphate-activated protein kinase is part of the regulation cascade of food intake by hormones and substrates at the hypothalamic level. A global energy shortage stimulates adenosine monophosphate-activated protein kinase in hypothalamic nuclei, which then transmits a message of hunger to the organism. Finally, an adenosine monophosphate-activated protein kinase has been discovered. This kinase (LKB1) phosphorylates and activates adenosine monophosphate-activated protein kinase and 11 adenosine monophosphate-activated protein kinase-related kinases. LKB1 is continuously active and the activation of adenosine monophosphate-activated protein kinase by LKB1 is then secondary to an action of adenosine monophosphate on adenosine monophosphate-activated protein kinase rather than on LKB1.
Acetyl coenzyme A (CoA) carboxylase (ACC) is an important regulator of fatty acid oxidation in the heart, since it produces malonyl CoA, a potent inhibitor of mitochondrial fatty acid uptake. Under conditions of metabolic stress, 5'adenosine monophosphate-activated protein kinase (AMPK), which is highly expressed in cardiac muscle, can phosphorylate and decrease ACC activity. Insulin, acting through inhibition of AMPK and stimulation of ACC, is capable of inhibiting myocardial fatty acid oxidation.