Purine nucleotide cycle

Phosphagen system (ATP-PCr) and purine nucleotide cycle (PNC)[1]

The Purine Nucleotide Cycle is a metabolic pathway in protein metabolism requiring the amino acids aspartate and glutamate. The cycle is used to regulate the levels of adenine nucleotides, in which ammonia and fumarate are generated.[2] AMP converts into IMP and the byproduct ammonia. IMP converts to S-AMP (adenylosuccinate), which then converts to AMP and the byproduct fumarate. 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.[2][3][4]

AMP is produced after strenuous muscle contraction when the ATP reservoir is low (ADP > ATP) by the adenylate kinase (myokinase) reaction.[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.[7]

  1. ^ Lewis AL, Guicherit OM, Datta SK, Hanten GR, Kellems RE (September 1996). "Structure and expression of the murine muscle adenylosuccinate synthetase gene". J Biol Chem. 271 (37): 22647–56. doi:10.1074/jbc.271.37.22647. PMID 8798436.
  2. ^ a b Lowenstein J.M. (1972). "Ammonia Production in Muscle and Other Tissues: the Purine Nucleotide Cycle". Physiological Reviews. 52 (2): 382–414. doi:10.1152/physrev.1972.52.2.382. PMID 4260884.
  3. ^ Salway, J.G. (2004). Metabolism at a glance (3rd ed.). Malden, Mass.: Blackwell. ISBN 1-4051-0716-2. OCLC 53178315.
  4. ^ Voet, Donald (2011). Biochemistry. Voet, Judith G. (4th ed.). Hoboken, NJ: Wiley. ISBN 978-0-470-57095-1. OCLC 690489261.
  5. ^ Cite error: The named reference :8 was invoked but never defined (see the help page).
  6. ^ Cite error: The named reference :3 was invoked but never defined (see the help page).
  7. ^ "Purine Synthesis : Synthesis of Purine RiboNucleotides". 2022-04-29. Retrieved 2022-12-14.