Purine nucleotide cycle
The fumarate goes on to produce ATP (energy) via oxidative phosphorylation as it enters the Krebs cycle and then the electron transport chain.
Lowenstein first described this pathway and outlined its importance in processes including amino acid catabolism and regulation of flux through glycolysis and the Krebs cycle.
[5][6] AMP is also produced from adenine and adenosine directly; however, AMP can be produced through less direct metabolic pathways, such as de novo synthesis of IMP or through salvage pathways of guanine (a purine) and any of the purine nucleotides and nucleosides.
IMP is synthesized de novo from glucose through the pentose phosphate pathway which produces ribose 5-P, which then converts to PRPP that with the amino acids glycine, glutamine, and aspartate (see Purine metabolism) can be further converted into IMP.
The first stage is the deamination of the purine nucleotide adenosine monophosphate (AMP) to form inosine monophosphate (IMP), catalysed by the enzyme AMP deaminase: 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: Finally, adenylosuccinate is cleaved by the enzyme adenylosuccinate lyase to release fumarate and regenerate the starting material of AMP: A recent study showed that activation of HIF-1α allows cardiomyocytes to sustain mitochondrial membrane potential during anoxic stress by utilizing fumarate produced by adenylosuccinate lyase as an alternate terminal electron acceptor in place of oxygen.
[7] The amino acid glutamate is used to neutralize the ammonia produced when AMP is converted into IMP.
Also, plasma glutamine (released from the kidneys) requires active transport into the muscle cell (consuming ATP).
When skeletal muscle is at rest (ADP
Without this enzyme, the excessive AMP buildup is initially due to the adenylate kinase (myokinase) reaction which occurs after a muscle contraction.
In AMP deaminase deficiency, excess adenosine is converted into uric acid in the following reaction: Myogenic hyperuricemia, as a result of the purine nucleotide cycle running when ATP reservoirs in muscle cells are low (ADP > ATP), is a common pathophysiologic feature of glycogenoses such as GSD-III, GSD-V and GSD-VII, as they are metabolic myopathies which impair the ability of ATP (energy) production within muscle cells.
In these metabolic myopathies, myogenic hyperuricemia is exercise-induced; inosine, hypoxanthine and uric acid increase in plasma after exercise and decrease over hours with rest.
