[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Purine nucleotide cycle (muscle)

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# 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

- [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/)
- [Purine degradation and salvage](https://durgical.com/en/biochemistry/pathways/purine-degradation-and-salvage/)

## Related conditions

- [Myoadenylate deaminase deficiency (AMP deaminase deficiency)](https://durgical.com/en/conditions/myoadenylate-deaminase-deficiency/)
- [McArdle disease (glycogen storage disease type V)](https://durgical.com/en/conditions/mcardle-disease/)

## Related

- [IMP (inosine monophosphate)](https://durgical.com/en/biochemistry/molecules/imp/)
- [Purine degradation and salvage](https://durgical.com/en/biochemistry/pathways/purine-degradation-and-salvage/)
- [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/)
- [ATP (adenosine triphosphate)](https://durgical.com/en/biochemistry/molecules/atp/)
- [Ammonia (ammonium)](https://durgical.com/en/biochemistry/molecules/ammonia/)
- [Creatine, phosphocreatine and creatinine](https://durgical.com/en/biochemistry/topics/creatine-phosphocreatine-and-creatinine/)
- [Exercise metabolism](https://durgical.com/en/biochemistry/topics/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Adenosine monophosphate deaminase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/adenosine-monophosphate-deaminase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [AMPD1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/ampd1/) (MedlinePlus, US National Library of Medicine, 2026); [AMPD1: AMP deaminase 1 (human)](https://www.uniprot.org/uniprotkb/P23109/entry) (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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