3-Guanidinopropionic Acid

3-Guanidinopropionic acid is a creatine analog that alters skeletal muscle energy expenditure. It reduces cellular ATP, creatine, and phosphocreatine levels and stimulates AMP-activated protein kinase (AMPK), activating PPARy coactivator 1a (PGC-1a).{27453,27454,27456,27452} PGC-1a activation results in enhanced expression of AMPK, as well as genes for oxidative phosphorylation, electron transport chain, and mitochondrial biogenesis, increasing oxidative muscle fibers, numbers of mitochondria, and motor performance.{27453,27455} 3-Guanidinopropionic acid evokes a shift from glycolytic to oxidative metabolism, increased cellular glucose uptake, and increased fatigue tolerance.{27454} In aged rats, reduced mitochondrial biogenesis in response to chronic activation of AMPK with 3-guanidinopropionic acid leads to metabolic insufficiency that can contribute to muscle loss.{27457,27455}