Muscle contraction and fatigue. The role of adenosine 5'-diphosphate and inorganic phosphate

Sports Med. 1997 May;23(5):287-305. doi: 10.2165/00007256-199723050-00003.


Though many explanations are offered for the fatigue process in contracting skeletal muscle (both central and peripheral factors), none completely explain the decline in force production capability because fatigue is specific to the activity being performed. However, one needs to look no further than the muscle contraction crossbridge cycle itself in order to explain a major contributor to the fatigue process in exercise of any duration. The byproducts of adenosine 5'-triphosphate (ATP) hydrolysis, adenosine 5'-diphosphate (ADP) and inorganic phosphate (Pi) are released during the crossbridge cycle and can be implicated in the fatigue process due to the requirement of their release for proper crossbridge activity. Pi release is coupled to the powerstroke of the crossbridge cycle. The accumulation of Pi during exercise would lead to a reversal of its release step, therefore causing a decrement in force production capability. Due to the release of Pi with both the immediate (phosphagen) energy system and the hydrolysis of ATP, Pi accumulation is probably the largest contributor to the fatigue process in exercise of any duration. ADP release occurs near the end of the crossbridge cycle and therefore controls the velocity of crossbridge detachment. Therefore, ADP accumulation, which occurs during exercise of extended duration (or in ischaemic conditions), causes a slowing of the rate constants (and therefore a decrease in the maximal velocity of shortening). in the crossbridge cycle and a reduced oscillatory power output. The combined effects of these accumulated hydrolysis byproducts accounts for a large amount of the fatigue process in exercise of any intensity or duration.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Adenosine Diphosphate / physiology*
  • Adenosine Triphosphate / physiology
  • Humans
  • Muscle Contraction*
  • Muscle Fatigue / physiology*
  • Muscle, Skeletal / physiology*
  • Phosphates / physiology*
  • Physical Education and Training


  • Phosphates
  • Adenosine Diphosphate
  • Adenosine Triphosphate