Creatine phosphate shuttle

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The creatine phosphate shuttle is an intracellular energy shuttle which facilitates transport of high energy phosphate from muscle cell mitochondria to myofibrils. This is part of phosphocreatine metabolism.

In mitochondria, ATP levels are very high as a result of glycolysis, TCA cycle, oxidative phosphorylation processes, whereas creatine phosphate levels are low. This makes conversion of creatine to phosphocreatine a highly favored reaction. Phosphocreatine is a very-high-energy compound. It then diffuses from mitochondria to myofibrils.

In myofibrils, during exercise (contraction) ADP levels are very high, which favors resynthesis of ATP. Thus phosphocreatine breakdown to creatine giving its inorganic phosphate for ATP formation.

At the onset of exercise PCr is broken down to provide ATP for muscle contraction. ATP hydrolysis results in products of ADP and inorganic phosphate. The inorganic phosphate will be transported into the mitochondrial matrix, while the free creatine passes through the outer membrane where it will be resynthesised into PCr. The antiporter transports the ADP into the matrix, while transporting ATP out. Due to the high concentration of ATP around the mitrochondrial creatine kinase, it will convert ATP into PCr which will then move back out into the cytoplasm to be converted into ATP (by cytoplasmic creatine kinase) to be used as energy for muscle contraction.

In some vertebrates, arginine phosphate plays a similar role.


  • Biochemistry, 3rd edition, Mathews, van Holde & Ahern.