Leucine (symbol Leu or L) is an

essential amino acid An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...

that is used in the biosynthesis of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s. Leucine is an α-amino acid, meaning it contains an α-

amino group In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...

(which is in the protonated −NH₃⁺ form under biological conditions), an α- carboxylic acid group (which is in the deprotonated −COO⁻ form under biological conditions), and a side chain isobutyl group, making it a

non-polar In chemistry, polarity is a separation of electric charge leading to a molecule or its chemical groups having an electric dipole moment, with a negatively charged end and a positively charged end. Polar molecules must contain one or more polar ...

aliphatic In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, ...

amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Human dietary sources are foods that contain protein, such as meats, dairy products, soy products, and beans and other legumes. It is

encoded In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ...

by the codons UUA, UUG, CUU, CUC, CUA, and CUG. Like

valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotona ...

and isoleucine, leucine is a

branched-chain amino acid A branched-chain amino acid (BCAA) is an amino acid having an aliphatic side-chain with a branch (a central carbon atom bound to three or more carbon atoms). Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine, and ...

. The primary metabolic end products of leucine metabolism are acetyl-CoA and acetoacetate; consequently, it is one of the two exclusively ketogenic amino acids, with lysine being the other. It is the most important ketogenic amino acid in humans. Leucine and

β-hydroxy β-methylbutyric acid β-Hydroxy β-methylbutyric acid (HMB), otherwise known as its conjugate base, , is a naturally produced substance in humans that is used as a dietary supplement and as an ingredient in certain medical foods that are intended to promote wou ...

, a minor leucine metabolite, exhibit

pharmacological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...

in humans and have been demonstrated to promote protein biosynthesis via the phosphorylation of the

mechanistic target of rapamycin The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. ...

(mTOR).

Dietary leucine

As a food additive, L-leucine has E number E641 and is classified as a

flavor enhancer A flavoring (or flavouring), also known as flavor (or flavour) or flavorant, is a food additive used to improve the taste or smell of food. It changes the perceptual impression of food as determined primarily by the chemoreceptors of the gust ...

Requirements

The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for

s in 2002. For leucine, for adults 19 years and older, 42 mg/kg body weight/day.

Sources

Health effects

As a dietary supplement, leucine has been found to slow the degradation of muscle tissue by increasing the synthesis of muscle proteins in aged rats. However, results of comparative studies are conflicted. Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men. More studies are needed, preferably ones based on an objective, random sample of society. Factors such as lifestyle choices, age, gender, diet, exercise, etc. must be factored into the analyses to isolate the effects of supplemental leucine as a standalone, or if taken with other branched chain amino acids (BCAAs). Until then, dietary supplemental leucine cannot be associated as the prime reason for muscular growth or optimal maintenance for the entire population. Both L-leucine and D-leucine protect mice against

epileptic seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

. D-leucine also terminates seizures in mice after the onset of seizure activity, at least as effectively as diazepam and without sedative effects. Decreased dietary intake of L-leucine lessens adiposity in mice. High blood levels of leucine are associated with insulin resistance in humans, mice, and rodents. This might be due to the effect of leucine to stimulate

mTOR The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. ...

signaling. Dietary restriction of leucine and the other BCAAs can reverse diet-induced obesity in wild-type mice by increasing energy expenditure, and can restrict fat mass gain of hyperphagic rats.

Safety

Leucine toxicity, as seen in decompensated

maple syrup urine disease Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine and ear ...

, causes delirium and neurologic compromise, and can be life-threatening. A high intake of leucine may cause or exacerbate symptoms of

pellagra Pellagra is a disease caused by a lack of the vitamin niacin (vitamin B3). Symptoms include inflamed skin, diarrhea, dementia, and sores in the mouth. Areas of the skin exposed to either sunlight or friction are typically affected first. Over t ...

in people with low

niacin Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...

status because it interferes with the conversion of L-tryptophan to niacin. Leucine at a dose exceeding 500 mg/kg/d was observed with

hyperammonemia Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to brain injury and death. It may be primary or secondary. Ammonia is a substance that contains nitrogen. It i ...

. As such, unofficially, a tolerable upper intake level (UL) for leucine in healthy adult men can be suggested at 500 mg/kg/d or 35 g/d under acute dietary conditions.

Pharmacology

Pharmacodynamics

Leucine is a

dietary In nutrition, diet is the sum of food consumed by a person or other organism. The word diet often implies the use of specific intake of nutrition for health or weight-management reasons (with the two often being related). Although humans are o ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

with the capacity to directly stimulate

myofibrillar A myofibril (also known as a muscle fibril or sarcostyle) is a basic rod-like organelle of a muscle cell. Skeletal muscles are composed of long, tubular cells known as muscle fibers, and these cells contain many chains of myofibrils. Each myofibr ...

muscle protein synthesis. This effect of leucine results from its role as an activator of the

(mTOR), a serine-threonine protein kinase that regulates protein biosynthesis and cell growth. The activation of mTOR by leucine is mediated through Rag GTPases, leucine binding to

leucyl-tRNA synthetase Leucyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the ''LARS'' gene. Function This gene encodes a cytosolic leucine-tRNA synthetase, a member of the class I aminoacyl-tRNA synthetase family. The encoded enzyme catal ...

, leucine binding to sestrin 2, and possibly other mechanisms.

Metabolism in humans

Leucine metabolism occurs in many tissues in the human body; however, most dietary leucine is metabolized within the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...

, and

muscle tissue Muscle tissue (or muscular tissue) is soft tissue that makes up the different types of muscles in most animals, and give the ability of muscles to contract. Muscle tissue is formed during embryonic development, in a process known as myogenesis. ...

. Adipose and muscle tissue use leucine in the formation of sterols and other compounds. Combined leucine use in these two tissues is seven times greater than in the liver. A small fraction of metabolism – less than 5% in all tissues except the

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...

where it accounts for about 33% – is initially catalyzed by leucine aminomutase, producing β-leucine, which is subsequently metabolized into (β-KIC), β-ketoisocaproyl-CoA, and then acetyl-CoA by a series of uncharacterized enzymes.

Synthesis in non-human organisms

Leucine is an essential amino acid in the diet of animals because they lack the complete enzyme pathway to synthesize it ''de novo'' from potential precursor compounds. Consequently, they must ingest it, usually as a component of proteins. Plants and microorganisms synthesize leucine from pyruvic acid with a series of enzymes: *

Acetolactate synthase The acetolactate synthase (ALS) enzyme (also known as acetohydroxy acid or acetohydroxyacid synthase, abbr. AHAS) is a protein found in plants and micro-organisms. ALS catalyzes the first step in the synthesis of the branched-chain amino acids ( ...

* Acetohydroxy acid isomero reductase *

Dihydroxyacid dehydratase The enzyme dihydroxy-acid dehydratase () catalyzes the chemical reaction :2,3-dihydroxy-3-methylbutanoate \rightleftharpoons 3-methyl-2-oxobutanoate + H2O This enzyme participates in valine, leucine and isoleucine biosynthesis and pantothenat ...

* α-Isopropylmalate synthase * α-Isopropylmalate

isomerase Isomerases are a general class of enzymes that convert a molecule from one isomer to another. Isomerases facilitate intramolecular rearrangements in which bonds are broken and formed. The general form of such a reaction is as follows: A–B � ...

* Leucine

aminotransferase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid co ...

Synthesis of the small, hydrophobic amino acid

also includes the initial part of this pathway.

Chemistry

Leucine is a branched-chain amino acid (BCAA) since it possesses an

side-chain that is not linear.

Racemic In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

leucine had been subjected to circularly polarized synchrotron radiation to better understand the origin of biomolecular asymmetry. An enantiomeric enhancement of 2.6% had been induced, indicating a possible photochemical origin of biomolecules'

homochirality Homochirality is a uniformity of chirality, or handedness. Objects are chiral when they cannot be superposed on their mirror images. For example, the left and right hands of a human are approximately mirror images of each other but are not their ow ...

. Meierhenrich: ''Amino acids and the asymmetry of life'', Springer-Verlag, 2008, .

Notes

References

External links

Leucine biosynthesis
{{Amino acid metabolism intermediates Proteinogenic amino acids Ketogenic amino acids Branched-chain amino acids Essential amino acids E-number additives