Leucine and mTORC: between acne and biceps. The benefits and importance of leucine, the most important amino acid for the human body: How to take leucine for medicinal purposes

Sirtuin

The sirtuin protein (Silent Information Regulator Transcript (SIRT)) is a NAD+ dependent enzyme that is sensitive to the cellular NAD+/NADH ratio and thus to the energy status of the cell. Of these, SIRT1 is a histone deacetylase that can alter the signaling of nuclear p53 proteins (cell cycle regulatory transcription factor), NF-kB (nuclear factor kappa-bi) and FOXO (class O forkhead box transcription factors) and can induce the mitochondrial biogenesis factor PGC-1α. Activation of SIRT1 is thought to be the most common. resveratrol) has a positive effect on longevity. Studies in rats have shown that leucine is responsible for the beneficial properties of dairy proteins, and this has a positive effect on longevity, improved health and a reduced risk of premature death. Results from blood serum data of patients who consumed large amounts of dairy products. showed that such a diet increases SIRT1 activity by 13% (adipose tissue) and 43% (muscle tissue). Both leucine metabolites (alpha-ketoisocaproic acid and hydroxymethylbutyrate monohydrate (HMB) are SIRT1 activators in the range of 30-100%, which is comparable to the effectiveness of resveratrol (2-10μM), but requires a higher concentration (0.5 mM). It has been noted that that mitochondrial biogenesis and leucine incubation occurs in fat and muscle cells, and disruption of SIRT1 reduces (but does not eliminate) leucine-induced mitochondrial biogenesis. Leucine metabolites are able to stimulate SIRT1 activity, and this mechanism underlies mitochondrial biogenesis. This mechanism is of moderate potency. .

Interaction with glucose metabolism

Glucose absorption

Leucine can promote the activation of insulin-induced protein kinase B (Akt), but phosphoinositol 3-kinase PI3K is required to first attenuate and inhibit it. This is the only way leucine preserves insulin-induced Akt activation). Since leucine also stimulates insulin secretion from the pancreas (insulin then activates PI3K), this is essentially of no practical importance. Under conditions where insulin is absent, 2 mM leucine and (to a lesser extent) its metabolite α-Ketoisocaproate appear to promote glucose uptake via PI3K/aPKC (atypical protein kinase C) and independently of mTOR (blocking MTOR does not affect the effect produced). In this study, stimulation is only 2-2.5mM for 15-45 minutes (resistance developed at 60 minutes) and is comparable in strength to physiological concentrations of basal insulin, but 50% less in strength (100 nM insulin). This mechanism of action is similar to that of isoleucine and has similar potency. However, leucine can also interfere with cellular glucose uptake, which is thought to be due to activation of mTOR signaling, which suppresses AMP-dependent kinase (AMPK) signaling (AMPK signaling mediates glucose uptake during periods of low cellular energy and exercise) and acts in concert with mTOR signaling to influence ribosomal protein S6 kinase (S6K). Signaling by MTOR/S6K causes degradation of IRS-1 (the first protein that carries the “signal” of the insulin-induced effect), through activation of proteasomal degradation of IRS-1 or by direct binding to IRS-1. This forms a negative closed-loop control system with insulin signaling feedback. Minimizing the negative effects on IRS-1 promotes leucine-induced glucose absorption, and this negative feedback explains why glucose is absorbed within 45-60 minutes and then suddenly inhibited. Since isoleucine does not have as much effect on mTOR activation and is thus a negative feedback pathway, it is isoleucine that mediates significant glucose uptake into muscle cells. Initially, leucine promotes the uptake of glucose into muscle cells for approximately 45 minutes, and then the process stops abruptly, somewhat reducing the overall effect. This sudden cessation is negative feedback that typically occurs after MTOR activation. Isoleucine is better than leucine at promoting glucose uptake due to less activation of mTOR.

Insulin secretion

Leucine is able to induce insulin secretion from the pancreas through its metabolite KIK. This insulin release is inhibited by other ARCs and two similar amino acids: norvaline and norleucine. Leucine is involved in the induction of insulin secretion, either as a supplement or in combination with glucose (for example, when taking leucine and glucose, there is an increase of 170% and 240%, respectively, and an increase of up to 450% when taking the combination). Despite the comparable potential of leucine and yohimbine, they are not combined due to their parallel mechanisms of action. Leucine is known to stimulate insulin secretion from the pancreas and is therefore the most potent ARC. On an equimolar basis (the same concentration of the molecule inside the cell), leucine has about the same potency as yohimbine, and two-thirds the potency of glucose. Leucine is a positive allosteric regulator of glutamate dehydrogenase (GDH), an enzyme that can convert some amino acids to ketoglutarate (α-ketoglutarate). This increases the cellular concentration of ATP (relative to ADP). An increase in ATP concentration levels causes an increase in insulin secretion through mechanisms that are independent of mTOR activation. The KIC metabolite can inhibit KATP channels and cause calcium fluctuations in pancreatic beta cells. Calcium release may also affect mTOR (a common target of leucine), and mTOR activation may suppress α2A receptor expression. Since α2A receptors suppress insulin secretion when activated, and overexpression induces diabetes, less expression of these receptors causes a relative increase in insulin secretion. This route is probably the most important from a practical point of view, since the mTOR antagonist of rapamycin can abolish leucine-induced insulin secretion and suppress insulin secretion itself. To stimulate insulin secretion from pancreatic beta cells, leucine works in two ways, the main of which is to reduce the influence of the negative regulator (2a receptors). A decrease in the influence of the negative regulator causes an increase in activity that is not treatable.

Leucine in bodybuilding

Protein synthesis

The main mechanism of action of leucine is stimulation of mTOR activity, and then stimulation of p70S6 kinase activity through PDK1. The p70S6 kinase then positively regulates protein synthesis. In addition, leucine is able to induce the activity of eukaryotic initiation factor (eIF, particularly eIF4E) and inhibits its inhibitory binding protein (4E-BP1), which increases protein translation, which has been confirmed after oral administration of leucine. Modulation of eIF thus enhances muscle protein synthesis driven by p70S6 kinase. Activation of mTOR is a well-known anabolic pathway, the action of which is associated with exercise (activation with a 1-2 hour time delay), insulin and caloric excess. Like other APCs, but unlike insulin, leucine does not stimulate protein kinase B (Akt/PKB) activity, which occurs between the insulin receptor and mTOR, (Akt and protein kinase B/PKB are interchangeable terms). Akt is able to upregulate eIF2B, which also positively promotes muscle protein synthesis driven by p70S6 kinase and, based on the lack of activation of Akt by leucine, is theoretically not as strong as if Akt signaling was activated in the same way as insulin. Activation of mTOR by leucine in humans has been confirmed following oral supplementation, as well as activation of p70S6K kinase. Akt activation studies have failed to detect any changes in human muscle functionality, implying that leucine-induced insulin release from the pancreas (a process that occurs in humans and Akt activation occurs through insulin) may not be relevant. Leucine is able to stimulate mTOR activity and its subsequent signaling of protein synthesis. Although Akt/PKB has a positive effect on mTOR activity (so when Akt is activated, it activates mTOR), leucine can act through a different pathway and activates mTOR without affecting Akt. Regardless, anything that activates mTOR will also affect p70S6 kinase and subsequently muscle protein synthesis. This anabolic effect of leucine has a greater effect on skeletal muscle than on liver tissue; physical exercise (muscle contractions) complements its beneficial effects. Some studies have shown that taking leucine before exercise is more effective than taking it at other times (for dramatically increasing protein synthesis). Leucine is the most powerful of all amino acids in stimulating muscle protein synthesis.

Atrophy/Catabolism

Leucine is known to promote muscle protein synthesis at low concentrations in vitro; when taken at higher concentrations, leucine can attenuate muscle wasting even though the rate of synthesis is stopped. This effect persists in the muscle and has been noted in diseases that have a negative impact on the muscle, such as cancer, as well as sepsis, burns and trauma. In these cases, the benefits of taking it depend on the dose.

Hyperaminoacidemia

Hyperaminoacidemia is a term used to refer to excess (hyper) amino acids in the blood (-emia), similarly, hyperleucinemia refers to excess leucine. Studies have shown that in older adults, leucine increases muscle protein synthesis independent of hyperaminoacidemia.

Sarcopenia

Sarcopenia is characterized by a decrease in protein content and an increase in fat content in skeletal muscle that occurs with age. One of the reasons for the occurrence of sarcopenia is a decrease in the metabolic response to the preservation of the muscle effect of L-leucine, which occurs with cellular aging. The negative impact of this effect can be minimized by adding L-leucine to foods containing protein.

Interactions with nutrients

Carbohydrate (carbohydrate)

When the insulin receptor is activated, it can activate mTOR indirectly through Akt. While Akt has a positive effect on protein synthesis driven by S6K1 kinase (which is activated during mTOR activation), leucine supplementation does not directly affect Akt activation the way insulin does in vitro. It has been noted that leucine infusion in humans does not significantly affect Akt activation in skeletal muscle, i.e., leucine-induced insulin secretion is not sufficient to stimulate Akt. Leucine interacts with metabolized glucose and lowers blood glucose levels and then affects the secretion of insulin from the pancreas. Interestingly, leucine does not combine with yohimbine in inducing insulin secretion due to parallel mechanisms of action. Leucine interacts with dietary carbohydrates and affects the activity of insulin secretion from the pancreas, and also interacts with insulin, which affects muscle protein synthesis.

Resveratrol

Resveratrol is a phenolic substance that is known to interact with sirtuin (mainly SIRT1), which is identical to leucine. The 0.5 mM KIC and HMB metabolites can induce SIRT1 to 30-100% of baseline levels, which is comparable to the activity of resveratrol at 2-10 μM. This is despite the fact that the combination of leucine (0.5 mM) or HMB (0.5 µM) and resveratrol (200 nM) is able to synergistically induce SIRT1 and SIRT3 activity in adipocytes (fat cells) and skeletal muscle cells. KIC is a more potent stimulant than HMB and interacts better with leucine than with HMB (possibly indicating KIC metabolism). When rats are fed a mixture of leucine (24 g/kg, up to 200% of the basal diet) or HMB (2 or 10 g/kg) with resveratrol (12.5 or 225 mg/kg) and then sacrificed in the fasted state, there is a decrease in fat mass and body weight is also synergistic. It was noted that incubation of resveratrol with leucine or HMB actually increased AMP-dependent kinase activity (42-55%, respectively) and promoted a small (18%) increase in fat oxidation, despite incubation with 5 µM glucose. The interaction of resveratrol and leucine (incubated or ingested) through activation of SIRT1 has a positive effect on mitochondrial biogenesis.

Citrulline

Citrulline may restore the rate of muscle protein synthesis and muscle function during aging and poor nutrition in rats, which is mediated through the mTORC1 pathway and is disrupted by the mTORC1 inhibitor known as rapamycin). It was not possible to significantly change the rate of leucine oxidation or protein synthesis in humans by supplementing with 0.18 g/kg citrulline for a week, but in other cases the same dose improves nitrogen balance in the human body in a fed state. The reason for this discrepancy is unknown. There is not much evidence for a direct activating effect of citrulline on mTOR, but it weakly induces proteins downstream of mTOR activation (including 4E-BP1) to levels below leucine. Citrulline has not yet been clinically proven to increase mTOR signaling, as its benefit is dependent on mTOR, in which case citrulline should be synergistic with leucine. Citrulline may signal leucine through mTOR, suggesting that they are synergistic. The effect of using this mixture by weightlifters has not yet been studied, so synergism is currently only an unconfirmed hypothesis.

Safety and toxicity

In a small study in which 5 healthy subjects were given stepwise doses of up to 1,250 mg/kg leucine (25 times the expected average body requirement for leucine), it was noted that oral doses of 500-1,250 mg caused an increase in serum ammonia, from -which is why the upper limit limit was set at 500 mg/kg (for a person weighing 150 pounds (68 kg) - 34 g).

Food supplement

As a food additive, L-leucine has an E number of E641 and is classified as a flavor enhancer.

Availability:

List of used literature:

Nutr Metab (Lond). 2012 Aug 22;9(1):77. doi:10.1186/1743-7075-9-77. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice. Bruckbauer A1, Zemel MB, Thorpe T, Akula MR, Stuckey AC, Osborne D, Martin EB, Kennel S, Wall JS.

Yeh YY. Ketone body synthesis from leucine by adipose tissue from different sites in the rat. Arch Biochem Biophys. (1984)

Van Koevering M, Nissen S. Oxidation of leucine and alpha-ketoisocaproate to beta-hydroxy-beta-methylbutyrate in vivo. Am J Physiol. (1992)

Dann SG, Selvaraj A, Thomas G. mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer. Trends Mol Med. (2007)

Nobukuni T, et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci U S A. (2005)

Greiwe JS, et al. Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle. Am J Physiol Endocrinol Metab. (2001)

Hannan KM, Thomas G, Pearson RB. Activation of S6K1 (p70 ribosomal protein S6 kinase 1) requires an initial calcium-dependent priming event involving the formation of a high-molecular-mass signaling complex. Biochem J. (2003)

Mercan F, et al. Novel role for SHP-2 in nutrient-responsive control of S6 kinase 1 signaling. Mol Cell Biol. (2013)

Fornaro M, et al. SHP-2 activates signaling of the nuclear factor of activated T cells to promote skeletal muscle growth. J Cell Biol. (2006)

Inoki K, et al. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. (2003)

Properties of leucine.

Leucine performs a number of important functions necessary for the human body, these include:

1. Necessary for the normal functioning of the liver;
2. In the postoperative period, it is used to restore skin and bones. Promotes rapid healing of wounds;
3. Reduces blood sugar levels. Leucine breaks down into glutamine and alanine, which maintain blood glucose levels;
4. Stimulates the growth of muscle tissue and prevents protein destruction. This function of leucine is important for athletes to build muscle.
5. Participates in carbohydrate metabolism.
6. To strengthen the immune system;
7. Prevents the onset of fatigue;
8. Effective in the fight against excess weight.

Daily value of leucine is 5000 mg for an adult, according to Skurikhin I.M.

What foods contain leucine?

This is found in protein foods.

To get the daily requirement of leucine you need to eat 200g of millet porridge + 115g of rabbit meat.

At leucine deficiency there is a mental disorder.

The reason for the lack of leucine is insufficient intake of vitamin B6 in the body.

Excess leucine causes excess ammonia in the body.

To a woman for wound healing, received during childbirth, you need to eat foods rich in leucine.

Leucine for nursing mothers.Feeding her husband, keeping the house in order, taking care of the baby - all this tires a young mother and leads to constant fatigue and lack of sleep. The easiest way to relieve fatigue is to eat foods containing essential amino acids, including leucine.

Leucine for children. Every mother is interested in how to protect her child from infections. Nutrition plays an important role in strengthening a child’s immunity, and may even be the first. A child must receive all essential substances from food, including leucine, in order to be healthy and successful.

Liked my article: Leucine amino acid for women and children", leave a comment.

Leucine is an essential amino acid. Discoveries in the field of chemistry had a significant impact on the development of science, industry, medicine, and sports. In recent years, the consumption of various supplements containing essential amino acid leucine. The fact is that it is necessary for protein synthesis in the body. First of all, that's why leucine and became widely known In sports. In addition, it is used for the recovery of patients after operations and the treatment of sports injuries. Meanwhile, leucine is still little known to most ordinary people. The time has come to correct this situation and talk in detail about this substance. In this article we will talk about beneficial properties of leucine, the use of this compound in various fields.

Leucine in optimal natural form and dosage is found in beekeeping products - such as pollen, royal jelly and drone brood, which are part of many natural vitamin and mineral complexes of the Parapharm company: Leveton P, Elton P, Leveton Forte ", "Apitonus P", "Osteomed", "Osteo-Vit", "Eromax", "Memo-Vit" and "Cardioton". That is why we pay so much attention to each natural substance, talking about its importance and benefits for a healthy body.

Leucine: a history of the important
scientific discovery

Let's touch on the history of this important scientific discovery. The French scientist Joseph Proust first encountered the effects of leucine in 1818, when he studied spoiled cheese. Already in 1820, the Frenchman Henri Braconneau managed to isolate this substance from rotten meat and wool. He also came up with this name. As you know, leucine (Latin name leucine) is an essential amino acid. This means that the human body does not know how to synthesize it independently. It is part of the body of all animals and most plants. Leucine also belongs to the group of branched chain amino acids (BCAA). It is precisely this feature of the chemical structure that makes it unique. The metabolism of this compound occurs not only in the liver, but also widely involves muscle tissue.

In its pure form, leucine is a colorless crystalline powder that is poorly soluble in water. It is part of certain dietary supplements and is also used in the treatment of many diseases. In addition, it is used for the recovery of patients after operations and the treatment of sports injuries. The substance is used not only in sports and medicine, but also in the food industry. Based on amino acids, scientists have created L-leucine – food additive E 641, which is classified as a flavor enhancer. In our body, this amino acid is mostly found in the muscles and liver. The total amount of BCAA in muscle tissue is about 35%.

Beneficial properties of leucine:
excellent immunomodulator and anti-catabolic

Meaning leucine for our body is huge, since it has many useful properties. Firstly, it is the main component for the construction of protein. Without leucine, the formation of our muscles would be impossible. It helps the athlete prevent muscle loss after exercise. Why is this happening? This amino acid stops catabolic reactions in the body. The regenerative capabilities of the body also increase, which helps recovery from injuries. Secondly, leucine - excellent immunomodulator.

Another important property of leucine is that it is one of the intermediate links for the formation of cholesterol and steroids. This substance is necessary for the synthesis of such an important enzyme as leptin, which is a fat burner. Leucine is also involved in the formation of hormones that have an anabolic effect. It is necessary for the production of insulin. That is, without this amino acid, muscles will not be built and sexual function will not function.

It should also be said about the stimulating effect of leucine on the central nervous system. This property is used to treat mental illness. In addition, the amino acid is necessary for the synthesis of growth hormone, which is so important for the child’s body. Therefore, children need to be given foods rich in leucine: cheeses, nuts, fish.

We can highlight the main beneficial properties of leucine:

• participates in protein synthesis;
• maintains the level of serotonin in the body, thanks to which we do not get tired longer;
• causes the production of insulin, just like sugar. The greatest effect is obtained when taken together BCAA dietary supplement and sugars, this sharply increases the synthesis of insulin.
• promotes rapid healing of wounds;
• strengthens the immune system;
• reduces blood sugar levels;
• normalizes liver function.

Leucine in sports : A bodybuilder's true love.
BCAA food supplement

It must be said that leucine is the main component (more than 70%) of the popular food additives. Today leucine increasingly used In sports. It's no secret that special Love have feelings for her bodybuilders. But if an athlete takes only leucine, then he will need to eat it with spoons, and such volumes are harmful to the kidneys. In addition, complete absorption of amino acids occurs in the presence of B vitamins. It has also been found that two other branched chain amino acids, isoleucine and valine, greatly enhance the effect of leucine.

Interestingly, leucine, along with other BCAAs, causes the body to release serine and threonine, which form a phosphorylating current. This effect stimulates protein synthesis, which is necessary for muscle growth. That's why this amino acid is so loved by bodybuilders and weightlifters. And indeed, correctly, using its capabilities, you can accelerate the growth of muscle mass. Companies producing BCAA food supplements, the most commonly used ratio of leucine to isoleucine and valine is 2:1:1. Trainers recommend taking this sports nutrition before and immediately after training to take advantage of the protein-carbohydrate window. A special effect can be achieved by consuming the supplement during the exercise itself - every 20 minutes.

Use of leucine in medicine

Due to its numerous properties leucine has long been used in medicine. It is part of medications that are used to treat liver diseases, anemia, and mental illness. Used as a corrector of amino acid imbalance in cancer patients. It is used in preoperative drug preparation, as well as to reduce the cytostatic effect of certain drugs. This is an excellent remedy for recovery after surgery and sports injuries.

Leucine is also given to patients to strengthen the immune system during radiotherapy and chemotherapy. This is a well-known remedy for the basic therapy of a wide variety of immunodeficiencies. It is often prescribed as a prophylactic for those who frequently take antibiotics. Can also be used to prevent colds.

In addition, leucine is used to treat Menkes disease, polio, and muscle degeneration. But leucine is not suitable for everyone; some patients have experienced side effects.

Strengthen muscles - lose weight.
Leucine for weight loss

BCAA food supplement– this is a good help for all lovers of a healthy lifestyle. For example, leucine can be used for weight loss. Let's say a little about how this anti-excess weight supplement works. Muscles can be called peculiar power plants that use fats and carbohydrates as fuel. If a person does not exercise and eats abundantly, his muscles degrade. As a result, these “power plants” consume little energy, and calories go into fat folds. If you decide to become slimmer, then leucine will help you cope with the task because it will strengthen your muscles.

Leucine tricks the body's systems into thinking its caloric intake is normal. As a result, the body does not try to retain fat masses. In addition, leucine is involved in the formation of the enzyme leptin, which is an effective fat burner. This enzyme is also called the “satiety hormone.” It inhibits the work of neuropeptide Y in the hypothalamus, which causes a feeling of hunger.

In which products
contains leucine

The main sources of leucine are animal products. It is no coincidence that they were able to isolate it from meat for the first time. There is a lot of leucine in cow, sheep and camel milk and all dairy products. Leucine is found in large quantities in eggs, red and black caviar.. If you do not eat meat, then fish will help you compensate for the lack of leucine, and special attention should be paid to oceanic species. However, strict supporters of a plant-based diet need not worry, since there are a number of “kill-free” foods rich in leucine. Such people need to eat legumes, grains (wheat), nuts, pumpkin seeds. It is worth paying attention to such a product as brown rice. If this product is not on hand, then regular peanuts will do. Bakery products are also an excellent source of leucine.

Daily value of leucine

A person should receive from 4 to 6 grams of this amino acid per day. Some sources indicate the following norm: 31 mg/kg of weight, for small children – 425 mg/kg. Let's translate this figure into food: per day you should eat 3 eggs, 100 grams of cottage cheese, 200 grams of meat, drink 300 grams of milk. But if you seriously decide to fight for sports titles, then you will have to eat six eggs a day, half a kilo of chicken meat, 200 grams of cottage cheese, and also drink about a liter of milk. Of course, it is quite difficult to eat such a quantity of food, which is why athletes so appreciated the appearance of protein mixtures or amino acids in powder form.

Lack of leucine in the body

A deficiency of this amino acid in the body provokes a number of pathological changes. Firstly, a negative nitrogen balance occurs in the body, which is especially harmful for children. Secondly, internal organs suffer: kidneys, liver, thyroid gland. Often for this reason, metabolism is disrupted, hypoglycemia may occur, and immunity may weaken. Typical signs lack of leucine in the body: headaches, dizziness, nervousness, fatigue, weight loss, slowdown in child development.

Excess leucine in the body.
Side effects
use of leucine

A number of Western countries have conducted serious research on leucine. The US has been particularly successful in this regard. For example, Columbia University conducted a series of experiments on rodents. It turned out that leucine causes an increase in muscle mass in rats and stimulates the reduction of fat deposits. In the same time excess leucine in the body impairs the absorption of other amino acids. As a result, we will lack many useful substances, such as tryptophan. This can cause irritability, depression, and insomnia.

We can highlight the work of American scientists: Robert A. Harris, Mandar Joshi. They found that leucine plays a leading role in BCAA supplements. This amino acid promotes protein synthesis and also slows down the destruction of protein structures. At the same time, an overdose of leucine should not be allowed.

An American researcher like E. Bloomstrand also believes that excess leucine dangerous for the body. If you consume BCAAs in large quantities, the concentration of ammonia in the plasma will increase. In turn, this effect can lead to fatigue and reduce motor functions. Therefore, those who play sports that require good coordination should be careful when taking this drug. An overdose of leucine negatively affects the functioning of the kidneys, which can lead to diseases over time. Basic side effects of leucine: skin rashes, itching. You should be aware of the possibility of overdose and prevent it. Taking leucine in its pure form does not make much sense and may even cause a decrease in muscle mass. You can get the required amount of this amino acid by consuming the drug. One of its components contains leucine and other beneficial substances.

Summarizing all of the above, we can conclude: without leucine, our life would be simply impossible. It is necessary for human health and is used in medicine, industry, and sports. In addition, leucine can help everyone who intends to.