CID 6106

C₆H₁₃NO₂

Leucine

C 6
H 13
N 1
O 2

Ball-and-stick Stick Space-filling

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22 atoms, 21 bonds.

IUPAC name: (2S)-2-amino-4-methylpentanoic acid
Molar mass: 131.175(18) g/mol
Atoms: 22
SMILES: CC(C)CC(C(=O)O)N
InChIKey: ROHFNLRQFUQHCH-YFKPBYRVSA-N
PubChem CID: 6106

Made of

C H N O

Structural formula of leucine. Each unlabelled corner is a carbon atom, and the four hydrogens on carbon are not drawn. Wedges come toward you, hashes go back. It shows which atoms are joined to which, not the shape. The model above shows the shape.

Leucine has to come from food. According to the Hazardous Substances Data Bank (HSDB), animals cannot build the carbon skeletons of the indispensable, or essential, amino acids from simpler molecules in the amounts needed. Leucine is one of the nine amino acids essential to humans, according to the US National Cancer Institute (NCI). MeSH, the US National Library of Medicine’s Medical Subject Headings, classes it as an essential amino acid.

MeSH also links leucine to the forming of haemoglobin, the oxygen-carrying protein of red blood cells. It is classed as a branched-chain aliphatic amino acid, one whose side chain forks and holds no aromatic ring. Its formula, C₆H₁₃NO₂, combines carbon, hydrogen, nitrogen and oxygen for a molar mass of 131.18 g/mol. Its white, glistening crystals sublime, turning straight to vapour, at 145–148 °C.

Structure and bonding

Six carbons, thirteen hydrogens, one nitrogen and two oxygens make an open chain that forks near its far end. In the Ball-and-stick view the alpha carbon, next to the acid group, holds the NH₂ group, a hydrogen, the COOH carbon and a CH₂ group. That CH₂ leads on to a CH carrying two CH₃ groups, a fork two carbons out from the alpha carbon. In the Space-filling view the methyl pair swells into a wide, rounded end.

Five of the six carbons hold four single bonds each, aimed at a tetrahedron’s corners as Chem1 describes. At the fork, the two methyls open to about 110° in PubChem’s computed model. The Stick view shows the acid carbon’s C=O, the only double bond, beside a single bond to the O–H oxygen.

The alpha carbon is the only stereocentre, a carbon whose groups can take two mirror-image arrangements, and the structural formula marks it with one hashed bond. The model draws the (2S) form, L-leucine, and the alanine page explains L and D. It also draws the uncharged molecule, with intact COOH and NH₂ groups; glycine’s page describes the charged forms an amino acid can also take.

Where it turns up

Milk, meat and eggs are among the protein-rich foods that supply leucine, according to MedlinePlus Genetics. Many foods contain it, and a shortage is rare. ChEBI, the Chemical Entities of Biological Interest database, records it as a metabolite, a substance cells make or use, in plants, algae, humans and the bacterium Escherichia coli. Commercial leucine is isolated from proteins such as gluten, casein and keratin, HSDB reports, or synthesised from isocaproic acid. The US Environmental Protection Agency (EPA) recorded a national volume of 41,827 pounds for 2023, down from 74,021 pounds in 2021.

Under 21 CFR 172.804, L-leucine may act as a lubricant in making aspartame sweetener tablets. In US animal feeds and veterinary drugs, leucine added as a nutrient has GRAS status, generally recognised as safe. Leucine also appears among the ingredients that US National Institutes of Health (NIH) fact sheets list for supplements sold with claims of boosting exercise and athletic performance.

Why it matters

Leucine’s breakdown begins with transamination, the handing-on of its amino group, catalysed by a branched-chain aminotransferase (BCAT); the product is alpha-ketoisocaproate (KIC). The branched-chain ketoacid dehydrogenase (BCKD) complex, active inside mitochondria, then strips a carboxyl group from KIC in an irreversible step, oxidative decarboxylation. Isoleucine and valine share the route, whose products can supply energy, according to MedlinePlus Genetics. In the brain, HSDB reports, leucine is also a precursor of fuel molecules, KIC itself and ketone bodies.

Maple syrup urine disease follows when that complex fails. Mutations in the BCKDHA, BCKDHB or DBT genes reduce or abolish its function, so leucine, isoleucine and valine escape normal breakdown. The unprocessed substances then reach levels toxic to the brain and other organs. The disorder is named for the sweet smell of affected babies’ urine, and the phenylalanine page explains the autosomal recessive pattern it follows.

Isovaleric acidaemia, a rare inherited disorder, involves another enzyme that helps process leucine. Its telltale sign is a smell of sweaty feet during acute illness. Isovaleric acid building up in the body causes that odour.

Properties

Properties of leucine Molar mass summed from IUPAC/CIAAW 2024 standard atomic weights; formula, atom and bond counts and PubChem's molecular weight from PubChem CID 6106.
Property	Value	Unit	Source
Molecular formula (Hill order)	C₆H₁₃NO₂
Molar mass	131.175(18) g/mol	g/mol	IUPAC/CIAAW 2024
Carbon atoms	6
Hydrogen atoms	13
Nitrogen atoms	1
Oxygen atoms	2
Bonds	21
Single bonds	20
Double bonds	1
PubChem molecular weight	131.17 g/mol	g/mol	PubChem

Safety

Leucine as part of everyday food is essentially harmless. All 208 reports collected by the European Chemicals Agency (ECHA) find that it meets no Globally Harmonized System (GHS) hazard criteria. HSDB records that when heated to decomposition it gives off toxic fumes of nitric oxide. The PubChem Laboratory Chemical Safety Summary for leucine sets out these findings.

Questions

Where does leucine's side chain branch?

At carbon 4. The name (2S)-2-amino-4-methylpentanoic acid starts from pentanoic acid, a chain of five carbons numbered from the acid carbon. Carbon 2 carries the amino group, NH₂, and carbon 4 carries an extra methyl group, CH₃. Carbon 4 is therefore the fork in the 3D model, a CH holding two CH₃ groups, one of which is carbon 5. The (2S) prefix fixes the arrangement around carbon 2.

What is a leucine zipper?

It is a DNA-binding motif, a recurring protein shape, made from two alpha helices, spiral stretches of a protein chain. The pair twist round each other into a coiled coil roughly eight turns long, then fork into a Y shape. Leucines recurring at every seventh position, a heptad repeat, line up along one face of each helix and meet in the Y's stem, which MeSH calls the zipper region.

What does leucine do in muscle?

It can act as a signal telling muscle to make more protein, according to the US Department of Agriculture's Agricultural Research Service (ARS). HSDB reports that it appears to act mainly by switching on the mTOR (mammalian target of rapamycin) signalling pathway, though how muscle cells sense leucine is unknown. Insulin switches on its own signal cascade, which leucine amplifies where a new protein chain starts. ARS-funded researchers are testing whether extra leucine helps preterm babies' muscles grow.

How common is maple syrup urine disease?

MedlinePlus Genetics estimates that it affects about 1 in 185,000 infants worldwide, and that it occurs much more often among the Old Order Mennonites. It is inherited in an autosomal recessive pattern. NICHD, the US National Institutes of Health's institute for child health and human development, lists maple syrup urine disease among the conditions added to newborn screening panels, the tests given to babies shortly after birth.

Made of the same elements

C₆H₁₃NO₂ Isoleucine 22 atoms, 21 bonds.
C₈H₁₁NO₂ Dopamine 22 atoms, 22 bonds.
C₉H₁₃NO₃ Epinephrine 26 atoms, 26 bonds.
C₉H₁₁NO₂ Phenylalanine 23 atoms, 23 bonds.
C₈H₉NO₂ Acetaminophen 20 atoms, 20 bonds.
C₉H₁₁NO₃ Tyrosine 24 atoms, 24 bonds.
C₅H₉NO₄ Glutamic acid 19 atoms, 18 bonds.
C₁₀H₁₂N₂O Serotonin 25 atoms, 26 bonds.

All 25 compounds made of carbon, hydrogen, nitrogen and oxygen

C₁₁H₁₂N₂O₂ Tryptophan 27 atoms, 28 bonds.
C₈H₁₀N₄O₂ Caffeine 24 atoms, 25 bonds.
C₃H₇NO₂ Alanine 13 atoms, 12 bonds.
C₅H₆N₂O₂ Thymine 15 atoms, 15 bonds.
C₁₂H₁₇NO DEET 31 atoms, 31 bonds.
C₁₃H₁₆N₂O₂ Melatonin 33 atoms, 34 bonds.
C₂H₅NO₂ Glycine 10 atoms, 9 bonds.
C₄H₄N₂O₂ Uracil 12 atoms, 12 bonds.
C₄H₅N₃O Cytosine 13 atoms, 13 bonds.
C₅H₅N₅O Guanine 16 atoms, 17 bonds.
C₅H₄N₄O₃ Uric acid 16 atoms, 17 bonds.
C₁₃H₂₁NO₃ Albuterol 38 atoms, 38 bonds.
CO(NH₂)₂ Urea 8 atoms, 7 bonds.
C₁₄H₁₈N₂O₅ Aspartame 39 atoms, 39 bonds.
C₁₄H₂₂N₂O Lidocaine 39 atoms, 39 bonds.
C₁₇H₂₁NO Diphenhydramine 40 atoms, 41 bonds.
C₂₀H₂₄N₂O₂ Quinine 48 atoms, 51 bonds.