Biochemistry of Exercise



The human body responds rapidly to the increased energy demands of exercise, in particular, the utilization of carbohydrates (sugars) and lipids (fats) as substrates that are oxidized to provide energy to muscle cells. Energy turnover in muscle increases more than 100-fold during exercise. Oxidation of glucose and fatty acids for muscle energy increases in proportion to the intensity of the exercise. The metabolic pathways that provide the energy for muscle contraction are controlled by complex interrelationships among hormones and other signaling molecules.

During moderate-to-hard endurance exercise, carbohydrates supply about 50% of energy requirements, primarily from glycogen stored in muscle tissue. Glycogen is the storage form of glucose, the primary carbohydrate utilized by the human body. Glycogen is broken down to glucose. Glycolysis is the breakdown of glycogen and glucose to supply cellular energy. As muscle glycogen stores become depleted, the liver releases more glucose into the bloodstream to fuel glycolysis in muscle.

The remaining energy is derived from the oxidation of fatty acids, including those already in the bloodstream as well as those mobilized from fat stores. As the intensity of the exercise decreases, for example, to a pace where a conversation could be held, less carbohydrate is used, and fat becomes the principal energy source.

When carbohydrates are limited, certain amino acids from muscle protein can be converted to glucose to be consumed as fuel. Although their energy contribution during short-term intense exercise is negligible, during prolonged exercise, amino acids provide 3–6% of the body's energy requirements. When carbohydrate availability is limited, amino acids may provide as much as 10% of the body's fuel.


The human body evolved for far more physical activity than is engaged in by most people in twentyfirst-century industrialized societies. Nevertheless, exercise probably puts more metabolic stress on the human body and affects more physiological systems than any other everyday activity.


The energy for muscle contraction comes from ATP (adenosine triphosphate). ATP is formed by aerobic (oxygen-dependent) respiration in the mitochondria of muscle cells, using energy released by glycolysis. Breaking of a high-energy bond in ATP releases ADP (adenosine diphosphate), inorganic phosphate (Pi), and one proton or hydrogen ion (Hþ). The protons are utilized by the mitochondria.

The final step of glycolysis yields two molecules of pyruvate along with protons from the splitting of ATP. Under conditions of sufficient oxygen, pyruvate is further metabolized in the mitochondria; however, under conditions of insufficient oxygen availability, as is common during intense exercise, lactate (lactic acid) builds up in muscle. Until recently, it was thought that this buildup of lactic acid caused acidosis, characterized by muscle soreness and fatigue, but it is now recognized that acidosis or muscle burn results from the release of more protons than can be utilized by the mitochondria. Pyruvate absorbs the protons to form lactate, temporarily slowing the development of acidosis and muscle fatigue. Lactate is metabolized within 15–30 minutes after exercise. Muscle cells also store energy in phosphate bonds in compounds such as phosphocreatine, which is known as the phosphagen system. Release of phosphate from these compounds to provide energy also produces protons that contribute to acidosis.

If insufficient oxygen is available for glucose metabolism, an oxygen debt is created. This can occur during intensive exercise or when sedentary people initiate even modest exercise. As heart and lung function improve, more oxygen becomes available for mitochondrial respiration, and glycogen and other substrates are metabolized more efficiently, increasing the capacity for exercise. Athletes consume oxygen and regenerate ATP more efficiently through mitochondrial respiration. Weightlifting and other anaerobic exercise creates an oxygen debt because the ATP demand in specific muscles outstrips their ability to aerobically produce ATP. High-intensity resistance exercise also utilizes fast-twitch muscle units that have fewer mitochondria for cellular respiration and proton uptake than slow-twitch or aerobic-endurance muscle fibers. The energy for fast-twitch muscles comes primarily from phosphagen and glycolytic anaerobic metabolism, creating an oxygen debt and possibly acidosis or muscle ache.

Fat and protein metabolism

Synthesis of new protein decreases during exercise; however, both glycogen synthesis and protein synthesis typically increase following exercise. Post-exercise protein synthesis in trained muscle tends to be specifically directed toward making more muscle fiber proteins, leading to muscle growth or hypertrophy. This response lasts for 24–48 hours after resistance exercise. However, protein synthesis decreases with age, leading to muscle loss, especially in women.


Although many different signaling molecules and pathways are involved in exercise biochemistry, AMPK (adenosine monophosphate-activated protein kinase) is considered to be a particularly important regulator of energy pathways in skeletal muscle. AMPK is an enzyme that senses fuel requirements and is highly activated in skeletal muscle during exercise. It also may be activated in adipose (fat) tissue, liver, and other organs. During exercise, activated AMPK initiates a cascade of complex effects that shift cellular biochemistry from nutrient storage to generation of ATP for energy. Activated AMPK stimulates glucose uptake, the breakdown of glycogen to glucose, and fatty-acid oxidation for generating energy. It also suppresses protein and lipid synthesis—including the synthesis of cholesterol, fatty acids, and triglycerides—and suppresses cell growth and proliferation to conserve energy.

AMPK is suspected of having a wide range of other biochemical effects during exercise. It helps regulate food intake and energy expenditure throughout the body and may stimulate glycolysis in heart muscle. AMPK also affects insulin sensitivity and gene and protein expression in various body tissues.

AMPK is activated when AMP (adenosine monophosphate) increases relative to ATP as the energy from ATP is used up for muscle contraction. During very intense exercise, large increases occur in the AMP concentration, and AMP binds to and activates AMPK in skeletal muscle. Exercise activates AMPK to a greater degree in men than in women. High levels of muscle glycogen inhibit AMPK activation during exercise; however, when glycogen stores are low, exercise increases the amount of AMPK in cells. Endurance training also may increase the amount of AMPK in muscles.


Hormones play major roles in the biochemistry of exercise.

Role in human health


Exercise can also:

Effects on gene expression

Research indicates that metabolites—the end products of converting carbohydrates, fats, proteins, and amino acids into energy—differ significantly following exercise, depending on an individual's fitness. It has been suggested that metabolites detectable after exercise may stimulate the expression of genes that affect the biochemistry of exercise. For example, a gene called nur77, which helps control the burning and storage of sugar and fat, is activated by exercise.

Excess acidity in muscle due to an accumulation of protons from ATP hydrolysis, causing muscle soreness and fatigue.
Adenosine diphosphate; a nucleotide with two phosphate groups that is converted to and from ATP to store and release cellular energy, respectively.
Activity that increases the body's requirement for oxygen, thereby raising respiration and heart rate.
Adenosine monophosphate; a nucleotide with one phosphate group that can be converted to and from ADP and ATP.
Adenosine monophosphate-activated protein kinase; an enzyme that is activated by AMP and that has a wide variety of physiological effects, including complex roles in the regulation of energy metabolism in muscle during exercise.
Activity that results in an oxygen debt.
Adenosine triphosphate; a nucleotide with three phosphate groups that supplies cellular energy by undergoing enzymatic hydrolysis to ADP and AMP.
Energy transformations and exchanges in the body.
Sugars, starches, celluloses, and gums that are a major source of calories and energy from foods.
A fat-soluble steroid alcohol found in animal fats and oils and produced in the body from saturated fats. Low-density lipoprotein (LDL), or “bad” cholesterol, has a high proportion of cholesterol and increases the risk of coronary heart disease. High-density lipoprotein (HDL), or “good” cholesterol, is primarily protein with small amounts of triglyceride and cholesterol and helps protect against heart disease.
Hydrocortisone; a corticosteroid stress hormone produced by the adrenal gland and released during exercise.
A nitrogen-containing organic acid that supplies muscles with energy.
A protein hormone produced by the pancreas that increases the rate of glycogen breakdown in the liver to raise blood sugar levels.
Animal starch; the form in which glucose is stored in the liver and muscle.
The breakdown of glucose or glycogen to pyruvate to supply cellular energy.
A substance, such as a protein, that is produced in one part of the body and travels through the bloodstream to affect another part of the body.
A protein hormone synthesized in the pancreas that is required for the metabolism of carbohydrates, lipids, and proteins and that regulates blood sugar levels.
Lactic acid; an end-product of anaerobic metabolism.
Fats; organic compounds that are stored in the body as energy reserves and that are important components of cell membranes.
The organelles in cells that produce energy through respiration.
Oxygen debt—
A cumulative deficiency of oxygen for metabolism that develops during intense exercise and must be replenished during rest.
Compounds such as phosphocreatine that supply muscles with energy during the initial stages of exercise and during high-intensity exercise.
Chains of amino acids that form enzymes, hormones, antibodies, and structural components of cells.
An elementary particle identical to the nucleus of a hydrogen atom (Ht).
Resistance exercise—
Strength training; exercise performed with weights or other resistance to muscle contraction.
Neutral fats; lipids formed from glycerol and fatty acids that circulate in the blood as lipoprotein. Elevated triglyceride levels contribute to the development of cardiovascular disease.
An end-product of protein degradation that is excreted in the urine.

Researchers have found that resistance exercise decreases age-related genetic abnormalities in the mitochondria of muscle cells. These abnormalities contribute to age-related muscle loss. Resistance exercise may stimulate the production of new muscle cells with normal mitochondria.

Exercise is well-known to help protect against stress-induced depression and brain injury. A 2014 study reported that exercise training causes the production of enzymes in skeletal muscle that can clear the blood of a harmful metabolite that accumulates during stress. This may be a biochemical mechanism by which exercise protects against and counteracts depression.

Common diseases and disorders

The biochemistry of exercise is a primary concern of serious athletes and sports physiologists. Exercise biochemistry, however, has important implications for sedentary individuals, as well as for those who engage in only moderate exercise. Exercise also has profound, and potentially dangerous, effects on the biochemistry of people with diabetes and other disorders of carbohydrate metabolism.

Since liver glycogen is important for maintaining normal blood sugar levels and can become depleted overnight, carbohydrates should probably be ingested before morning exercise. Too much food or sugar before exercising, however, can reduce the rate at which fluids leave the stomach to replace those lost through sweat.

See also Carbohydrates ; Exercise .




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American College of Sports Medicine, 401 W. Michigan St., Indianapolis, IN, 46202-3233, (317) 6379200, Fax: (317) 634-7817, .

Margaret Alic, PhD

  This information is not a tool for self-diagnosis or a substitute for professional care.