Purine nucleotide cycle

The Purine Nucleotide Cycle is a metabolic pathway in which fumarate is generated from aspartate in order to increase the concentration of Krebs cycle intermediates. The pathway was first described by John Lowenstein, who demonstrated its role in increasing the rate of oxidative phosphorylation in skeletal muscle.

Outline
The cycle is composed of three enzyme-catalysed reactions. The first stage is the deamination of the purine nucleotide Adenosine monophosphate (AMP) to form inosine monophosphate (IMP), catalysed by the enzyme AMP deaminase:


 * AMP + H2O → IMP + NH4+

The second stage is the formation of adenylosuccinate from IMP and the amino acid aspartate, which is coupled to the energetically favourable hydrolysis of GTP, and catalysed by the enzyme adenylosuccinate synthetase:


 * Aspartate + IMP + GTP → Adenylosuccinate + GDP + Pi

Finally, Adenylosuccinate is cleaved by the enzyme adenylosuccinate lyase to release fumarate and regenerate the starting material of AMP:


 * Adenylosuccinate → AMP + Fumarate