The purine nucleotide cycle occurs in the cytosol (a gel-like substance) of the sarcoplasm of skeletal muscle, and in the myocyte's cytosolic compartment of the cytoplasm of cardiac and smooth muscle. The cycle occurs when ATP reservoirs run low (ADP > ATP), such as strenuous exercise, fasting or starvation.
Proteins catabolize into amino acids, and amino acids are precursors for purines, nucleotides and nucleosides which are used in the purine nucleotide cycle. The amino acid glutamate is used to neutralize the ammonia produced when AMP is converted into IMP. Another amino acid, aspartate, is used along with IMP to produce S-AMP in the cycle. Skeletal muscle contains amino acids for use in catabolism, known as the free amino acid pool; however, inadequate carbohydrate supply and/or strenuous exercise requires protein catabolism to sustain the free amino acids.
When the phosphagen system (ATP-PCr) has been depleted of phosphocreatine (creatine phosphate), the purine nucleotide cycle also helps to sustain the myokinase reaction by reducing accumulation of AMP produced after muscle contraction in the below reaction.
During muscle contraction: 
: HO + ATP → H + ADP + P (Mg assisted, utilization of ATP for muscle contraction by ATPase)
: H + ADP + CP → ATP + Creatine (Mg assisted, catalyzed by creatine kinase, ATP is used again in the above reaction for continued muscle contraction)
: 2 ADP → ATP + AMP (catalyzed by adenylate kinase/myokinase when CP is depleted, ATP is again used for muscle contraction)  
Muscle at rest:
: ATP + Creatine → H + ADP + CP (Mg assisted, catalyzed by creatine kinase)
: ADP + P → ATP (during anaerobic glycolysis and oxidative phosphorylation)
AMP can dephosphorylate to adenosine and diffuse out of the cell; the purine nucleotide cycle may therefore also reduce the loss of adenosine from the cell since nucleosides permeate cell membranes, whereas nucleotides do not.