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
- Glycogen metabolism
- Fatty acid β-oxidation
- Krebs cycle (citric acid cycle)
- Electron transport chain and oxidative phosphorylation
Related conditions
- McArdle disease (glycogen storage disease type V)
- Tarui disease (muscle phosphofructokinase deficiency)
- Carnitine palmitoyltransferase II (CPT-II) deficiency
- Type 2 diabetes mellitus
- Lactic acidosis
Related
- AMP-activated protein kinase (AMPK)
- Glycogen phosphorylase
- Lactate
- Cori cycle
- ATP (adenosine triphosphate)
- Adrenaline
- Fed, fasting and starvation states
- Insulin signalling
- 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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Exercise and Physical Fitness: MedlinePlus (MedlinePlus, US National Library of Medicine, 2026); Physical activity (World Health Organization, 2026); PRKAA2: 5'-AMP-activated protein kinase catalytic subunit alpha-2 (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.