7. Metabolism of Muscle Tissue


1. Metabolism of muscle tissue
2. Diagnostics in muscle diseases


Metabolism of muscle tissue

Muscle tissue is a significant consumer of nutrients and oxygen. Its consumption is unquestionably dependent on how intensively the muscle is working. During intense exercise muscles alone account for 60 % of total oxygen consumption. Muscle cells are also able to function effectively for a period of time without oxygen supplies -  anaerobically. For that reason muscle cell contains notable amounts of muscle glycogen and phosphocreatine.

Energy sources in muscle tissue

Sarcoplasm contains an amount of ATP that is sufficient for 1 second of intensive exercise. ATP is replenished from the following sources:

1) Phosphocreatine

2) Muscle glycogen: activation of glycogen phosphorylase by an increase in intracellular concentration of Ca2+ is replenished during muscle relaxation

3) Nutrients from circulation: glucose, fatty acids, ketones

4) Amino acids (from circulation and internal muscle amino acids)

In addition to the individual metabolic pathways, two other enzymes are important for ATP production:

1) Creatine kinase (CK)

Phosphocreatine + ADP ↔ creatine + ATP

2) Adenylate kinase


Types of muscle fibers and their metabolic differences

Fibers of striated muscle can be divided into two basic types – red and white:

Red muscle fibers („slow“, first type fibers)

Red muscle fibers are characterized by a high content of myoglobin (oxygen binding protein), mitochondria and a rich vascular supply. This predetermines the red fibers to specialize in aerobic metabolism during aerobic exercise (e.g. cycling, swimming, marathon running, maintaining muscle tone – back muscles). Their fundamental energy source is β-oxidation of fatty acids. As exercise intensity increases so does the muscles dependence on carbohydrates for energy.

White muscle fibers („fast“, second type fibers)

White muscle fibers contain less myoglobin and mitochondria and have a poor blood supply compared to red muscle fibers. On the contrary, they are rich in glycogen and enzymes of glycolysis. Therefore they are very effective for powerful and rapid contraction of short duration fueled by anaerobic metabolism. As the fibers contract the pace of glycogenolysis and anaerobic glycolysis increases rapidly. Nascent lactate accumulates in the muscle and results in pain and muscle fatigue – therefore they are ideal for an anaerobic load, which can be  executed „in one breath” like a leap, weightlifting or sprint. Lactate is released from muscle into the bloodstream, which carries it to the liver. In the liver, lactate is converted to glucose by gluconeogenesis. . The glucose then travels back to the muscle through the bloodstream – the so-called Cori cycle. Lactate also serves an energetic substrate for heart.

The majority of striated muscles in the human body are formed by the combination of both types of fibers. Their operation depends on oxygen supply – anaerobic and aerobic metabolism is alternated according to the intensity and length of exercise. Some muscles have a prevalence of one type of fiber.

The effect of hormones on muscle metabolism

Muscle metabolism is modulated by numerous hormones. Insulin increases the entry of glucose (GLUT-4) and fatty acids into muscle cells. Concurrently insulin also activates anabolic processes – formation of glycogen, triglycerides and proteins. Catecholamines activate muscle glycogenolysis and lipolysis .

Muscle fatigue

Intensive muscle exercise causes muscle fatigue. The degree of fatigue is subject to a local increase in lactate concentration and pH decrement. This is an important protective mechanism, which should alert an individual of the danger of a muscle cells damage. Muscle fatigue can be decreased by sympathetic activation (or catecholamines). Trained individuals have a shifted threshold of muscle fatigue because their muscle are habituated to greater loads of stress (e.g. higher energy stores).

Metabolism of amino acids in muscle

Striated muscle is capable of metabolising branched-chain amino acids (BCAA – Val, Leu, Ile). Their carbon backbones are utilized in energy metabolism, their amino groups serve to synthesize alanine, glutamate and glutamine. Alanine and glutamine are released into the bloodstream (alanine concentration is approximately 0.3 mmol/l, concentration of glutamine is  approximately 0.6 mmol/l). Glutamine serves as the primary transport form for ammonia in an organism. Alanine and glutamine are deaminated in the liver and the nascent ammonia is transformed here into urea. The liver is capable of resynthesizing alanine into glucose – the alanine cycle is complete.

Amino acids become an important source of energy during intense exercise or prolonged fasting. Glucocorticoids (cortisol) stimulate protein catabolism of muscle proteins – released amino acids are utilized as substrates for gluconeogenesis.

Creatine and phosphocreatine

Creatine is synthesized in kidney and liver from glycine, arginine, and S-adenosylmethionine  (SAM). In muscle, creatine is phosphorylated (ATP consumption , catalyzed by creatine kinase) to phosphocreatine. Non-enzymatic cyclization of creatine forms creatinine – a waste product excreted in the urine.


Diagnostics in muscle diseases

The following markers are used to diagnose muscle disease:

1) Creatine kinase (CK) –  in order to differentiate lesion sites the following creatine kinase isoenzymes activities are measured:

a) CK-MM – located in skeletal muscles

b) CK-MB – located in the myocardium

2) Troponin I and T – currently the most specific cardiac markers, peak concentrations are reached about 14 hours after myocardial infarction

3) Myoglobin – released into the bloodstream after damage to skeletal or cardiac muscle  (e.g. crush syndrome), its massive release into the bloodstream can cause kidney failure. As a cardiac marker its specificity is low, but it reaches peak concentration in just 6 hours after myocardial infarction.

Subchapter Authors: Josef Fontana and Petra Lavríková