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[Biochemistry](https://durgical.com/en/biochemistry/) · Topic

# Exercise metabolism

Muscle switches fuel with intensity and duration: phosphocreatine, glycogen with lactate, and then oxidised glucose and fat.

Updated 2026-11-01

## Key facts

- First seconds: ATP and phosphocreatine (creatine kinase). Maximal effort up to 1–2 minutes: anaerobic glycolysis with lactate.
- Prolonged moderate exercise: oxidation of glycogen, glucose and more and more fatty acids.
- Contraction Ca²⁺ and AMP activate muscle glycogen phosphorylase; adrenaline adds to it through cAMP.
- AMPK moves GLUT4 to the membrane during exercise without needing insulin.
- Endurance training adds mitochondria, capillaries and capacity to oxidise fat.

## In detail

- Phosphocreatine regenerates ATP instantly (creatine kinase) but runs out in about 10 seconds of maximal effort.
- In a sprint, fast glycolysis makes pyruvate faster than mitochondria can use it: lactate leaves for the blood and the liver turns it back into glucose (Cori cycle).
- As intensity rises, the share of carbohydrate oxidised rises; at moderate intensity and in long efforts fat contributes more (respiratory quotient 1.0 with carbohydrate and about 0.7 with fat).
- During exercise insulin falls and glucagon, adrenaline, cortisol and GH rise: the liver delivers glucose and adipose tissue releases fatty acids.
- AMPK, activated by falling ATP, inhibits acetyl-CoA carboxylase, lowers malonyl-CoA and lets fatty acids into the mitochondrion (CPT1).
- Fatigue in long efforts coincides with muscle glycogen depletion; acidity and inorganic phosphate contribute in short, intense efforts.

## Clinical notes

- McArdle disease: without muscle phosphorylase, cramps appear early in exercise with no lactate rise, and a 'second wind' comes when glucose and fatty acids arrive in the blood.
- CPT2 deficiency causes muscle pain and dark urine (myoglobinuria) in long exercise or fasting.
- Exercise improves insulin sensitivity and is a central part of type 2 diabetes care.
- Creatine kinase rises in blood after hard exercise and far more in rhabdomyolysis.

## Pathways

- [Glycolysis](https://durgical.com/en/biochemistry/pathways/glycolysis/)
- [Glycogen metabolism](https://durgical.com/en/biochemistry/pathways/glycogen-metabolism/)
- [Fatty acid β-oxidation](https://durgical.com/en/biochemistry/pathways/fatty-acid-oxidation/)
- [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/)
- [Electron transport chain and oxidative phosphorylation](https://durgical.com/en/biochemistry/pathways/electron-transport-chain-and-oxidative-phosphorylation/)

## Related conditions

- [McArdle disease (glycogen storage disease type V)](https://durgical.com/en/conditions/mcardle-disease/)
- [Tarui disease (muscle phosphofructokinase deficiency)](https://durgical.com/en/conditions/tarui-disease/)
- [Carnitine palmitoyltransferase II (CPT-II) deficiency](https://durgical.com/en/conditions/carnitine-palmitoyltransferase-ii-deficiency/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)
- [Lactic acidosis](https://durgical.com/en/conditions/lactic-acidosis/)

## Related

- [AMP-activated protein kinase (AMPK)](https://durgical.com/en/biochemistry/enzymes/amp-activated-protein-kinase/)
- [Glycogen phosphorylase](https://durgical.com/en/biochemistry/enzymes/glycogen-phosphorylase/)
- [Lactate](https://durgical.com/en/biochemistry/molecules/lactate/)
- [Cori cycle](https://durgical.com/en/biochemistry/topics/cori-cycle/)
- [ATP (adenosine triphosphate)](https://durgical.com/en/biochemistry/molecules/atp/)
- [Adrenaline](https://durgical.com/en/biochemistry/molecules/adrenaline/)
- [Fed, fasting and starvation states](https://durgical.com/en/biochemistry/topics/fed-fasting-and-starvation-states/)
- [Insulin signalling](https://durgical.com/en/biochemistry/topics/insulin-signalling/)
- [Carnitine shuttle](https://durgical.com/en/biochemistry/topics/carnitine-shuttle/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which system supplies energy in the first 10 seconds of maximal effort?

Stored ATP and phosphocreatine, which creatine kinase uses to regenerate ATP.

## How does exercising muscle take up glucose when insulin is low?

Contraction and AMPK move GLUT4 to the membrane through an insulin-independent route.

## Why does lactate not rise with exercise in McArdle disease?

Because without muscle glycogen phosphorylase, glycogen is not broken down and does not feed glycolysis.

## Which respiratory quotient means mostly fat is being oxidised?

A value near 0.7; pure carbohydrate gives 1.0.

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

Sources: [Exercise and Physical Fitness: MedlinePlus](https://medlineplus.gov/exerciseandphysicalfitness.html) (MedlinePlus, US National Library of Medicine, 2026); [Physical activity](https://www.who.int/news-room/fact-sheets/detail/physical-activity) (World Health Organization, 2026); [PRKAA2: 5'-AMP-activated protein kinase catalytic subunit alpha-2 (human)](https://www.uniprot.org/uniprotkb/P54646/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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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/topics/exercise-metabolism/
