AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing protein k inase responsible for coordinating metabolism and energy demand. In rodents , exercise accelerates fatty acid metabolism, enhances glucose uptake, and stimulates nitric oxide (NO) production in skeletal muscle. AMPK phosphoryl ates and inhibits acetyl-coenzyme A (CoA) carboxylase (ACC) and enhances GL UT-4 translocation. It has been reported that human skeletal muscle malonyl -CoA levels do not change in response to exercise, suggesting that other me chanisms besides inhibition of ACC may be operating to accelerate fatty aci d oxidation. Here, we show that a 30-s bicycle sprint exercise increases th e activity of the human skeletal muscle AMPK-alpha1 and -alpha2 isoforms ap proximately two- to threefold and the phosphorylation of ACC at Ser(79) (AM PK phosphorylation site) similar to8.5-fold. Under these conditions, there is also an similar to5.5-fold increase in phosphorylation of neuronal NO sy nthase-mu (nNOS mu) at Ser(1451). These observations support the concept th at inhibition of ACC is an important component in stimulating fatty acid ox idation in response to exercise and that there is coordinated regulation of nNOS mu to protect the muscle from ischemia/metabolic stress.