Isoleucine occupies a special function in protein metabolism. The essential amino acid is predominantly involved in building new tissues and is very effective for enhanced protein biosynthesis in muscles and liver.Isoleucine plays an essential role in:
- Strength and endurance sports
- Stress
- Diseases and diet
Isoleucine as an energy supplier in strength and endurance sportsIsoleucine enters the hepatocytes (liver cells) after absorption via the portal vein. By splitting off ammonia (NH3), isoleucine is converted into alpha-keto acids. Alpha-keto acids can be used for energy production. On the other hand, since isoleucine is both a glucogenic and ketogenic amino acid, alpha-keto acids can be used as a precursor for the synthesis of succinyl-coenzyme A as well as acetyl-coenzyme A. The intermediate of the citrate cycle succinyl-CoA serves as a substrate for gluconeogenesis (new glucose formation) in liver and muscles. Acetyl-CoA is an essential starting product of lipo- and ketogenesis (formation of fatty acids and ketone bodies). Glucose as well as fatty acids and ketone bodies represent important energy suppliers for the body – especially during physical exertion. The erythrocytes (red blood cells) and the renal medulla are completely dependent on glucose for energy. The brain only partially, because in starvation metabolism it can obtain up to 80% of energy from ketone bodies. When glucose and fatty acids are broken down in the muscles, ATP (adenosine triphosphate) is formed, the cell’s most important energy carrier. When its phosphate bonds are hydrolytically cleaved by enzymes, ADP or AMP is formed. The energy released in this process enables chemical, osmotic or mechanical work, such as muscle contractions. Due to its essential function in energy production, a deficiency of isoleucine is associated with muscle weakness, listlessness and fatigue, among other symptoms. After processing in the liver, almost 70% of all amino acids entering the blood are BCAAs. They are rapidly absorbed by the muscles. In the first three hours after a high-protein meal, isoleucine, leucine, and valine account for about 50-90% of the muscles’ total amino acid intake. Isoleucine is extremely important for muscle tissue regeneration and maintenance. BCAAs are a component of about 35% of the contractile proteins – actin and myosin – in muscle. Isoleucine stimulates the release of insulin from the beta cells of the pancreas (pancreas). High insulin concentrations in the blood accelerate amino acid uptake into myocytes (muscle cells). Increased transport of amino acids into myocytes leads to the following processes:
- Increased protein buildup in the muscles
- Rapid decrease in the concentration of the stress hormone cortisol, which promotes muscle breakdown and inhibits amino acid uptake into muscle cells
- Better storage of glycogen in the myocytes, maintenance of muscle glycogen.
Finally, an intake of foods rich in isoleucine, leucine and valine results in optimal muscle growth and maximum accelerated recovery. In addition to isoleucine, the amino acids arginine and phenylalanine, leucine and valine also exhibit insulin-stimulating effects, with leucine being the most potent. Biotin, vitamin B5 (pantothenic acid) and vitamin B6 (pyridoxine) are essential for the breakdown and conversion of BCAAs. Only as a result of a sufficient supply of these vitamins can the branched-chain amino acids be optimally metabolized and used. Several studies show that both endurance sports and strength training require an increased protein intake. To maintain a positive nitrogen balance – corresponding to tissue regeneration – the daily protein requirement is between 1.2 and 1.4 g per kg body weight for endurance athletes and 1.7-1.8 g per kg body weight for strength athletes. During endurance sports, isoleucine, leucine and valine in particular are used for energy production. The supply of energy from these amino acids increases when the glycogen stores in the liver and muscles become increasingly depleted as sporting activity progresses. Strength athletes should also ensure a high intake of branched-chain amino acids, especially before training. In this way, the body does not draw on its own BCAAs from the muscles during physical exertion and protein catabolism is prevented. The supply of BCAAs is also recommended after training.Isoleucine quickly raises insulin levels after the end of exercise, stops protein breakdown caused by previous exercise, and initiates renewed muscle growth. In addition, BCAAs result in greater fat loss. To get the most out of BCAAs in terms of muscle building, they should all be taken together and in conjunction with other protein. Isolated intake of isoleucine or leucine or valine may temporarily disrupt protein biosynthesis for muscle building. Consumption of BCAAs alone should be viewed critically, especially prior to endurance training, due to oxidation under stress and urea attack. The breakdown of 1 gram of BCAAs produces about 0.5 grams of urea. Excessive urea concentrations put a strain on the organism. Therefore, in connection with BCAAs intake, increased fluid intake is crucial. With the help of plenty of fluid, the urea can be quickly eliminated via the kidneys. Finally, an increased intake of isoleucine, leucine, or valine should be weighed during endurance exercise. Performance improvements for the endurance athlete only occur when BCAAs are used during altitude training or training in high heat. As a result of a high protein intake or physical stress, high amounts of nitrogen in the form of ammonia (NH3) are produced as a result of protein breakdown. This has a neurotoxic effect in higher concentrations and can result, for example, in hepatic encephalopathy. This condition is a potentially reversible brain dysfunction that results from inadequate detoxification function of the liver. Most importantly, isoleucine and leucine can increase the breakdown of toxic ammonia in the muscles-a significant benefit for the athlete. In the liver, arginine and ornithine perform this task. Scientific studies have shown that the administration of 10-20 grams of BCAAs under stress can delay mental fatigue. However, there is still no evidence that branched-chain amino acids lead to improved performance. Similarly, improved adaptation to exercise has not been demonstrated.
Isoleucine in situations of stress-induced exercise
During increased physical and exercise stress, such as injury, illness, and surgery, the body breaks down protein at an increased rate. Increased intake of isoleucine-rich foods can counteract this. Protein catabolism is stopped by isoleucine rapidly raising insulin levels, promoting amino acid uptake into cells and stimulating protein buildup. Protein anabolism is important for the formation of new body tissue or for the healing of wounds and to increase resistance to infections. Finally, isoleucine helps to regulate metabolism and the body’s defenses. In this way, important muscle functions can be supported during increased physical stress.
Isoleucine in diseases and diets
Acutely ill or convalescent patients have an increased need for essential amino acids. Due to a frequently inadequate intake of high-quality protein and restricted food intake, increased intake of isoleucine, leucine, and valine in particular is recommended. BCAAs can accelerate convalescence – recovery. Specific benefits of isoleucine occur in the following conditions:
- Cirrhosis of the liver
- Coma hepaticum
- Schizophrenia
- Phenylketonuria (PKU)
- Dystones syndrome
Coma hepaticum is the most severe form of hepatic encephalopathy – stage 4 – a reversible brain dysfunction resulting from inadequate detoxification function of the liver. Nerve damage in the central nervous system results in, among other things, unconsciousness without reaction to pain stimuli (coma), extinction of muscle reflexes and muscle rigidity with flexion and extension posture. Liver hypofunction leads to insulin excess, which provides for increased transport of amino acids, including isoleucine, to the muscles. Consequently, the isoleucine concentration in the blood is lowered. Since BCAAs and the essential amino acid tryptophan use the same transport system in the blood, i.e. the same carrier proteins, tryptophan can occupy many free carriers due to the low serum isoleucine level and be transported toward the blood-brain barrier.L-tryptophan competes with 5 other amino acids at the blood-brain barrier for entry into the nutrient fluid of the brain – namely with the BCAAs and aromatic amino acids phenylalanine and tyrosine. Due to the excess of tryptophan in the brain, phenylalanine, the precursor of catecholamines, such as the stress hormones epinephrine and norepinephrine, is also displaced in addition to tyrosine and the BCAAs. Finally, tryptophan can cross the blood-brain barrier unhindered. Because of phenylalanine displacement, sympathetic activation in the brain is absent, limiting catecholamine synthesis in the adrenal medulla. In the central nervous system, tryptophan is converted to serotonin, which functions as a tissue hormone or neurotransmitter in the central nervous system, intestinal nervous system, cardiovascular system, and blood. Increased levels of tryptophan eventually result in increased serotonin production. In cases of liver dysfunction, excessive amounts of serotonin cannot be broken down, which in turn leads to severe fatigue and even unconsciousness. Increased intake of isoleucine prevents increased production of serotonin via the mechanism of tryptophan displacement both in the blood and at the blood-brain barrier and inhibition of tryptophan uptake into the nutrient fluid of the brain. In this way, isoleucine counteracts the occurrence of coma hepaticum. By reducing the level of tyrosine in the blood, BCAAs, isoleucine can be used in orthomolecular psychiatry, for example in schizophrenia. Tyrosine is the precursor of dopamine, a neurotransmitter in the central nervous system from the catecholamine group. An excessively high concentration of dopamine in certain brain areas leads to central nervous hyperexcitability and is associated with the symptoms of schizophrenia, such as ego disorders, thought disorders, delusion, motor restlessness, social withdrawal, emotional impoverishment and weakness of will. Isoleucine, leucine and valine can also provide specific benefits in the treatment of phenylketonuria (PKU). PKU is a congenital metabolic disorder in which the amino acid phenylalanine cannot be broken down. In affected individuals, phenylalanine accumulates in the organism, which can lead to nerve damage and subsequently to a severe mental development disorder with epilepsy – spontaneously occurring seizures. A high serum isoleucine level decreases the binding of phenylalanine to transport proteins in the blood and its concentration at the blood-brain barrier, reducing phenylalanine uptake into the brain. Thus, with the help of BCAAs, an abnormally high phenylalanine concentration can be normalized both in the blood and in the brain. Furthermore, with the help of branched-chain amino acids, there are advantages for people with so-called dystonic syndrome (dyskinesia tarda). This disorder is characterized, among other things, by involuntary movements of the facial muscles, for example, spasmodic sticking out of the tongue, spasms of the gullet, spasmodic reclination of the head and hyperextension of the trunk and extremities, torticollis, as well as torsion-like movements in the neck and shoulder girdle area while maintaining consciousness. Diet-conscious individuals, who often have an inadequate supply of protein or consume primarily foods low in isoleucine, have an increased need for BCAAs. The intake of isoleucine, leucine and valine should eventually be increased so that the body does not draw on its own protein reserves, such as those from the liver and muscles, in the long term. Protein loss in the muscles leads to a decrease in metabolically active muscle tissue. The more a dieting person loses muscle mass, the more the basal metabolic rate decreases and the body consumes fewer and fewer calories. Ultimately, a diet should aim to preserve muscle tissue or even increase it through exercise. At the same time, the percentage of body fat should be reduced. During a diet, BCAAs help to prevent protein breakdown and thus a drop in the basal metabolic rate, as well as to increase fat breakdown. Immune defense is largely maintained. A new study at Arizona State University suggests that a diet high in branched-chain amino acids can increase basal metabolic rate by 90 kilocalories daily. Extrapolated over a year, this would mean a weight loss of about 5 kg without calorie reduction or exercise.
Isoleucine as a starting building block for the synthesis of nonessential amino acids
Reactions by which amino acids are newly formed are called transaminations. In this process, the amino group (NH2) of an amino acid, such as isoleucine, alanine, or aspartic acid, is transferred to an alpha-keto acid, usually alpha-ketoglutarate. Alpha-ketoglutarate is thus the acceptor molecule. The products of a transamination reaction are an alpha-keto acid, such as pyruvate or oxaloacetate, and the nonessential amino acid glutamic acid or glutamate, respectively. In order for transaminations to take place, special enzymes are required – the so-called transaminases. The two most important transaminases include alanine aminotransferase (ALAT), also known as glutamate pyruvate transaminase (GPT), and aspartate aminotransferase (ASAT), also known as glutamate oxaloacetate transaminase (GOT). The former catalyzes the conversion of alanine and alpha-ketoglutarate to pyruvate and glutamate. ASAT converts aspartate and alpha-ketoglutarate to oxaloacetate and glutamate. Coenzyme of all transaminases is the vitamin B6 derivative pyridoxal phosphate (PLP). PLP is loosely bound to the enzymes and is essential for optimal transaminase activity. Transamination reactions are localized in liver and other organs. The transfer of alpha-amino nitrogen from isoleucine to an alpha-keto acid by transaminases with the formation of glutamate occurs in muscle. Glutamate is considered the “hub” of amino nitrogen metabolism. It plays a key role in the formation, conversion and breakdown of amino acids. Glutamate is the starting substrate for the synthesis of proline, ornithine and glutamine. The latter is an essential amino acid for nitrogen transport in the blood, protein biosynthesis, and for the excretion of protons in the kidney in the form of NH4. Glutamate the major excitatory neurotransmitter in the central nervous system. It binds to specific glutamate receptors and can thus control ion channels. In particular, glutamate increases the permeability of calcium ions, an important prerequisite for muscle contractions. Glutamate is converted to gamma-aminobutyric acid (GABA) by splitting off the carboxyl group – decarboxylation. GABA belongs to the biogenic amines and is the most important inhibitory neurotransmitter in the gray matter of the central nervous system. It inhibits neurons in the cerebellum.