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 forms ...

that is used in the

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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

amino group In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

(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 (in which all ...

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

codon Genetic code is a set of rules used by living cells to translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets or codons) into proteins. Translation is accomplished by the ribosome, which links prote ...

s UUA, UUG, CUU, CUC, CUA, and CUG. Leucine is named after the

Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assumed last common ancestor of all kno ...

word for "white": ''λευκός'' (''leukós'', "white"), after its common appearance as a white powder, a property it shares with many other

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

. 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 deproton ...

and

isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...

, leucine is a

branched-chain amino acid A branched-chain amino acid (BCAA) is an amino acid having an aliphatic substituent, 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, isoleu ...

. The primary metabolic end products of leucine metabolism are

acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidation, o ...

and

acetoacetate Acetoacetic acid ( IUPAC name: 3-oxobutanoic acid, also known as acetonecarboxylic acid or diacetic acid) is the organic compound with the formula CHCOCHCOOH. It is the simplest beta-keto acid, and like other members of this class, it is unstable ...

; consequently, it is one of the two exclusively

ketogenic amino acid A ketogenic amino acid is an amino acid that can be degraded directly into acetyl-CoA, which is the precursor of ketone bodies and myelin, particularly during early childhood, when the developing brain requires high rates of myelin synthesis. This ...

s, with

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

being the other. It is the most important ketogenic amino acid in humans. Leucine and β-hydroxy β-methylbutyric acid, a minor leucine

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

, 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 Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the produc ...

via the

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

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 Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives, such as vinegar ( pickling), salt ( salting), smoke ( smoking) and sugar ( crystallization), have been used f ...

, L-leucine has

E number E numbers, short for Europe numbers, are codes for substances used as food additives, including those found naturally in many foods, such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...

E641 and is classified as a

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

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 A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...

, 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 stand-alone, or if taken with other

s (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 A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

. 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 a rare, inherited metabolic disorder that affects the body's ability to metabolize amino acids due to a deficiency in the activity of the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex. It parti ...

, 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 friction and radiation are typically affected first. Over tim ...

in people with low

niacin Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan. Nicotinic acid is also a prescription medication. Amounts f ...

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, or high ammonia levels, is a metabolic disturbance characterised by an excess of ammonia in the blood. Severe hyperammonemia is a dangerous condition that may lead to brain injury and death. It may be primary or secondary. Ammoni ...

. 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 ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 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 myofib ...

muscle

protein synthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critica ...

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

(mTOR), a serine-threonine protein kinase that regulates

and

cell growth Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

. 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 metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

adipose tissue Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

, and

muscle tissue Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to contract. ...

. Adipose and muscle tissue use leucine in the formation of

sterol A sterol is any organic compound with a Skeletal formula, skeleton closely related to Cholestanol, cholestan-3-ol. The simplest sterol is gonan-3-ol, which has a formula of , and is derived from that of gonane by replacement of a hydrogen atom on ...

s 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 ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone. The ...

, 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 nonhuman 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 Pyruvic acid (CH3COCOOH) is the simplest of the keto acids, alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate acid, conjugate base, CH3COCOO−, is an metabolic intermediate, intermediate in several m ...

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 In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually uti ...

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 pantothenate ...

* α-Isopropylmalate synthase * α-Isopropylmalate isomerase * 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 c ...

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 a mixture that has equal amounts (50:50) 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 r ...

leucine had been subjected to circularly polarized

synchrotron radiation Synchrotron radiation (also known as magnetobremsstrahlung) is the electromagnetic radiation emitted when relativistic charged particles are subject to an acceleration perpendicular to their velocity (). It is produced artificially in some types ...

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

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