Branched Chain Amino Acids: Definition, Benefits, Mechanism and List

Amino acid is the basic unit of protein and plays an important role in the body's tissue composition. It is an important part of the body's survival, nutrition, metabolic regulation, immunity, and information transmission. Branched-chain amino acids (BCAA) are essential nutrients for maintaining the growth of animals. They are the basic components of proteins and have special physiological and biological functions, such as anti-fatigue, promoting protein synthesis, improving immunity, anti-oxidation and regulating glucose metabolism.

What are Branched Chain Amino Acids?

Branched chain amino acid (BCAA) is an essential amino acid with a special side chain structure, including leucine (Leu), isoleucine (Ile) and valine (Val). They are not synthesized by our bodies and therefore must be obtained from diet. Approximately 35% of the essential muscle protein and 40% of the total amino acids required by mammals are composed of these branched chain amino acids. The three branched chain amino acids together or leucine alone can stimulate protein synthesis and also inhibit protein breakdown.

Unlike other amino acids, branched-chain amino acids are mainly catabolized in extrahepatic tissues. Branched-chain amino acids play a role in regulating protein synthesis and turnover and maintaining glutamate-glutamine levels in the body. Under strenuous and traumatic conditions, branched-chain amino acids are oxidized, which limits their availability in tissues. This condition affects glutamate-glutamine pools and protein synthesis machinery in the body. Therefore, BCCA supplementation is becoming a nutritional strategy to treat many diseases. Many studies have found that branched-chain amino acid administration improves the health of patients with different diseases, even if they don't work in some cases. There are also some reports showing that elevated branched-chain amino acids are associated with the pathogenesis of disease.

Branched Chain Amino Acids List

• Isoleucine

Isoleucine is one of the essential amino acids for the human body and originated from scientific research in the 19th century. It was originally isolated from plants and subsequently found in animal tissues. Early scientists' research on isoleucine mainly focused on its chemical properties and nutritional value. However, it was not until the early 20th century, with the development of biochemistry and genetics, that people began to have a deep understanding of the biosynthesis and metabolism of isoleucine.

• Leucine

Leucine was first discovered by scientists at the end of the 19th century. At that time, researchers conducted in-depth studies on the composition and properties of proteins, including the study of amino acids. In 1886, Dutch biologist Cornelis Bernardus Wieringa isolated leucine from muscle tissue. Due to its high solubility in water, Dutch chemist Emil Fischer identified leucine as the first neutral amino acid to be discovered.

• Valine

Valine was discovered in the early 20th century. In 1900, German chemist Adolf von Baeyer discovered valine while studying the chemical structure of phenylalanine. Because valine has a variety of important physiological functions, it is also widely used in the medical field. Valine can be used to treat certain diseases, such as liver disease, kidney disease, and neurological diseases. In addition, valine can be used to make nutritional supplements and treat certain genetic diseases.

How Do Branched Chain Amino Acids Work?

Although most amino acids are degraded in the liver, BCCA is primarily catabolized by extrahepatic tissues (muscle, fat, kidneys, and brain). First, BCAA undergoes a reversible transamination reaction under the catalysis of branched chain amino acid transaminase (BCAT) to form the corresponding branched chain ketoacids (BCKAs). BCKAs then undergo an irreversible oxidative decarboxylation reaction catalyzed by the branched chain ketoacid dehydrogenase complex (BCKDH) to generate the corresponding branched chain acyl-CoA ester. Branched-chain acyl-CoA esters undergo dehydrogenation and water addition to form β-hydroxyacyl-CoA, which then enters metabolic pathways such as the tricarboxylic acid cycle. Leu is a ketogenic amino acid, and its metabolite is acetoacetate and acetyl-CoA; Ile is a ketogenic and glycogenic amino acid, and its metabolite is propionyl-CoA; Val is a glycogenic amino acid, and its metabolite is succinyl-CoA. Therefore, BCAA mainly enters the tricarboxylic acid cycle through glucogenesis and ketogenesis, thereby participating in the conversion between sugar, fat and protein.

Benefits of Branched Chain Amino Acids

Experimental evidence suggests that sepsis, cancer, trauma, and burns enhance oxidation of BCAAs and decrease BCAA levels. In these cases, BCAA supplementation is necessary to maintain physiologically relevant levels of BCAAs in the body. Although BCCA supplementation has been reported to be beneficial in the treatment of certain diseases, there are also diseases for which branched-chain amino acids should be restricted. BCAA not only supplements nutrition, but also has many biological effects, such as regulating the balance between pro-inflammatory and anti-inflammatory cytokines, alleviating oxidative stress, improving the body's immunity, regulating glucose metabolism, etc.

• Anti-fatigue Effects of BCAA

As an essential amino acid, BCAA has anti-central fatigue effects, can delay exercise-induced fatigue, speed up the body's recovery after exercise, and thereby improve body performance. In addition, BCAA can also be used as a sports nutrition preparation to promote the synthesis of protein and energy, enhance lactic acid metabolism, and improve the muscle strength and endurance of test subjects. In the weight-bearing swimming test of mice, supplementary feeding of BCAA (dose 2 g/kg body weight) can significantly extend the weight-bearing swimming time of mice; after heavy-load exercise, BCAA in the muscles is rapidly consumed, and the lactate dehydrogenase content increases. Feeding BCAA can reduce the damage to body cells, inhibit the production of lactate dehydrogenase, and improve the endurance and exercise ability of mice.

• BCAA Promotes Protein Synthesis

BCAA plays an important role in regulating protein synthesis and inhibiting protein breakdown. Research shows that supplementing with branched-chain amino acids helps build muscle by improving muscle protein synthesis. BCAA regulates protein synthesis mainly by activating the mammalian target of rapamycin (mTOR). mTOR belongs to the phosphatidylinositol-3-kinase-related kinase superfamily and is a central regulatory factor in the pathogenesis of various diseases. There are two different complexes, mTORC1 and mTORC2. BCAA can phosphorylate and activate the downstream signaling factors eukaryotic initiation factor 4E-binding protein (4E-BP1) and ribosomal S6 kinase 1 (S6K1) by activating mTORC1. Studies have shown that 3.6 mmol/L Leu can significantly increase the phosphorylation levels of 4E-BP1 and S6K1, the key downstream factors of the mTOR pathway in dairy pancreatic acinar cells.

• BCAA Improves Animal Immune Function

The immune system of the animal body is the third line of defense of the animal body, including immune organs, immune tissues, immune cells and immune active factors. It has the functions of defense, regulating physiology, protecting the body's steady-state balance, and removing foreign bodies and pathogens in time. Insufficient BCAA intake can cause abnormal immune function and lead to damage to your own tissues and organs. Supplementing BCAA can enable macrophages and lymphocytes in mesenchymal stem cells to regulate the immune function of cells by regulating immune active factors. The synthesis of glutamine from BCAA is a key factor in maintaining immune cell function and can provide raw materials for the synthesis of glutamine. Glutamine improves immune function by reducing the release of inflammatory cytokines and reducing lymphoid organ apoptosis in septic rats. In recent years, research on how BCAA improves the immune function of animals has become a research hotspot and is of great significance to ensuring animal health.

• Anti-oxidative Stress Effects of BCAA

When the body is exposed to harmful stimuli, the balance between oxidants and antioxidants in the body is destroyed, and the free radicals generated exceed the scavenging capacity of the body's antioxidant system, leading to oxidative stress in the body. BCAA plays a significant role in scavenging free radicals and enhancing the body's antioxidant capacity. BCAA can upregulate reactive oxygen species (ROS) defense system genes and reduce ROS production. BCKAs can also alleviate the oxidative damage caused by oxidative stress to cells by inhibiting cell necrosis and promoting mitochondrial energy metabolism. It can be seen that BCAA can effectively scavenge free radicals and increase the body's antioxidant enzyme content, thereby playing an antioxidant role. In addition, BCAA can also reduce the production of free radicals by reducing the calcium load within cells, thereby protecting antioxidant enzyme activity.

• BCAA Regulates Sugar Metabolism

BCAA can also serve as a signaling molecule to regulate the body's glucose metabolism, fat deposition, insulin sensitivity and maintain energy balance. It is of great significance to body health and livestock and poultry production. Among them, Leu's role in regulating glucose and lipid metabolism is more obvious. When maintaining energy balance in the body, BCAA can regulate glucose uptake and insulin sensitivity. But when there is too much energy, the ability of cells to degrade BCAA will be inhibited, leading to the accumulation of BCAA by inhibiting the expression of BCKDH. Many metabolic diseases in the body are closely related to BCAA imbalance. BCKDH is the rate-limiting enzyme for BCAA catabolism and is essential for maintaining BCAA homeostasis. Excessive intake of BCAA will activate the mTORC1 pathway, phosphorylate S6K1, thereby phosphorylating insulin receptor substrate 1 (IRS1), reducing the activity of IRS1, resulting in the inhibition of PI3K/Akt signaling, reducing insulin sensitivity and glucose original synthesis. On the contrary, BCAA deficiency can improve insulin sensitivity and glycogen synthesis.

Currently, branched-chain amino acids are used as supplements for various pathophysiological conditions. Although their role in protein synthesis is inconsistent across studies, it is clear that branched-chain amino acids can reduce negative nitrogen balance in living systems. There is evidence that branched-chain amino acids can prevent muscle loss in both young and old adults. In addition, branched-chain amino acid supplementation is beneficial for patients with cirrhosis and liver cancer. In separate studies, branched-chain amino acids have also been used in critically ill patients with severe burns, sepsis, surgery, and trauma.

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