Biochemistry · Topic
Purine nucleotide cycle (muscle) !
In working muscle, AMP is deaminated to IMP and then rebuilt. The loop keeps ATP high, feeds the Krebs cycle and releases ammonia.
Updated 2026-11-01
Key facts
- Step 1: AMP deaminase (AMPD1 in muscle) turns AMP into IMP + NH₃.
- Step 2: adenylosuccinate synthetase joins IMP to aspartate using GTP → adenylosuccinate.
- Step 3: adenylosuccinate lyase releases fumarate and gives back AMP.
- Net: aspartate + GTP + H₂O → fumarate + GDP + Pi + NH₃; fumarate refills the Krebs cycle (anaplerosis).
- Removing AMP pulls adenylate kinase (2 ADP ⇌ ATP + AMP) toward ATP during intense exercise.
In detail
- 1. In hard exercise ATP is used faster than it is made; adenylate kinase rescues some ATP from ADP, forming AMP.
- 2. AMP deaminase keeps AMP low, so the adenylate kinase reaction keeps running toward ATP.
- 3. Muscle lacks a complete urea cycle and has little glutamate dehydrogenase activity; this cycle is a main source of ammonia in exercising muscle.
- 4. The fumarate produced enters the Krebs cycle as an intermediate, helping oxidative metabolism.
- 5. Brain also runs the cycle, and IMP links it with purine breakdown to hypoxanthine and uric acid (blood urate rises after heavy exercise).
- Also called
- AMP deaminase cycle, Lowenstein cycle
Clinical notes
- AMP deaminase deficiency (myoadenylate deaminase deficiency) is common and usually silent; some people have cramps and muscle pain with exercise.
- Forearm exercise test: in AMPD1 deficiency lactate rises but ammonia does not; in McArdle disease ammonia rises but lactate does not.
- Adenylosuccinate lyase deficiency is a rare neurological disease with succinyl-purines in urine.
Pathways
Related conditions
- Myoadenylate deaminase deficiency (AMP deaminase deficiency)
- McArdle disease (glycogen storage disease type V)
Related
- IMP (inosine monophosphate)
- Purine degradation and salvage
- Krebs cycle (citric acid cycle)
- ATP (adenosine triphosphate)
- Ammonia (ammonium)
- Creatine, phosphocreatine and creatinine
- Exercise metabolism
Test yourself
Think of the answer, then tap the question to see it.
What are the net products of one turn of the purine nucleotide cycle?
Fumarate and ammonia, using aspartate and GTP.
Which enzyme of the cycle is deficient in the most common inherited muscle enzyme defect?
AMP deaminase (AMPD1), causing myoadenylate deaminase deficiency.
How does the cycle help keep ATP available during intense exercise?
Removing AMP pulls the adenylate kinase reaction (2 ADP ⇌ ATP + AMP) toward ATP formation.
What does a forearm exercise test show in AMP deaminase deficiency?
A normal rise in lactate but no rise in ammonia.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Adenosine monophosphate deaminase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); AMPD1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); AMPD1: AMP deaminase 1 (human) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.