One of the three branched-chain amino acids — and the one whose single misplacement in hemoglobin causes sickle cell disease, one of biology's most famous single-amino-acid mutations.
Symbol
Val · V
Discovered
1901
Mol. Weight
117.15 g/mol
Essential
Yes
V
Discovery: From Valerian Root
L-Valine
Valine was first isolated in 1901 by German chemist Emil Fischer — the same prolific researcher responsible for establishing much of the foundational knowledge of amino acid chemistry. He extracted it from the hydrolysis products of casein and named it valine after valerian root (Valeriana officinalis), from which some protein material used in early experiments was derived. The name stuck, though valine itself is present in all proteins, not specifically in valerian.
Fischer's work in the early 1900s was extraordinary in scope: he systematically characterized amino acid after amino acid, developed methods for synthesizing peptides, and established the peptide bond as the linkage between amino acids in proteins. Valine was one of many discoveries from his extraordinarily productive laboratory during this period. Today valine is recognized as a branched-chain essential amino acid with a stimulant role in muscle metabolism, and the three branched-chain amino acids together constitute more than two-thirds of the amino acids found in body proteins.
🔴 One Amino Acid, One Disease
Sickle cell disease is caused by a single nucleotide change in the gene for the beta chain of hemoglobin. That mutation changes codon 6 from GAG (glutamic acid) to GUG (valine). The result: one valine residue replaces one glutamic acid residue in a protein of 146 amino acids.
Glutamic acid carries a negative charge; valine is nonpolar and hydrophobic. This tiny chemical difference — one charge replaced by a hydrophobic surface — creates a sticky patch on the hemoglobin molecule. When oxygen levels fall, these patches on neighboring hemoglobin molecules adhere to each other, forming long rigid fibers that distort red blood cells into the characteristic sickle shape. Sickled cells block capillaries, break down prematurely, and cause the painful crises of sickle cell disease.
The valine substitution was identified in 1956 by Vernon Ingram — the first demonstration that a genetic disease could be traced to a single amino acid change in a specific protein. It was one of the founding discoveries of molecular medicine.
Identifiers and Properties of Valine
Identity
IUPAC Name(2S)-2-Amino-3-methylbutanoic acid
FormulaC₅H₁₁NO₂
Mol. Weight117.15 g/mol
CAS Number72-18-4
MDL NumberMFCD00064220
Physical
Melting point315 °C
Solubility85 g/L (20 °C)
pKa₁ (COOH)2.29
pKa₂ (NH₃⁺)9.74
pI6.02
Rf (BuOH/AcOH/H₂O = 12:3:5)0.61
Identifiers
Canonical SMILESCC(C)C(C(=O)O)N
Isomeric SMILESCC(C)[C@@H](C(=O)O)N
InChIKeyKZSNJWFQEVHDMF-BYPYZUCNSA-N
MetabolismGlucogenic only
EssentialYes
The Smallest Branched-Chain Amino Acid
Valine is the smallest of the three branched-chain amino acids (BCAAs), alongside leucine and isoleucine. Its side chain is an isopropyl group — two methyl groups branching from the beta carbon. This compact branching gives valine a rigid, space-filling shape that is particularly useful in the hydrophobic core of folded proteins, where it contributes to structural packing without being as bulky as leucine or isoleucine.
Like the other BCAAs, valine is metabolized primarily in muscle tissue rather than in the liver. Under prolonged exercise or caloric restriction, muscles can oxidize valine directly for energy. Valine's carbon skeleton enters the citric acid cycle as succinyl-CoA, making it strictly glucogenic — unlike leucine (purely ketogenic) or isoleucine (both glucogenic and ketogenic), all of valine's breakdown products feed into glucose synthesis pathways.
Valine and Penicillin: An Unexpected Connection
Valine is an essential building block for penicillin and related beta-lactam antibiotics — not in the human body, but in the mold Penicillium that produces them. The biosynthesis of penicillin starts with a tripeptide composed of alpha-aminoadipic acid, cysteine, and valine. This tripeptide is then cyclized and modified to form the beta-lactam ring responsible for penicillin's antibacterial activity. Every molecule of penicillin ever produced by fermentation had valine as one of its three precursor amino acids.
Functions of L-Valine in the Body
As an essential branched-chain amino acid, valine must come from food and participates in several important physiological processes.
Muscle energy and preservation
Valine supplies muscle tissue with an additional source of glucose during physical activity, particularly during prolonged exercise when glycogen stores begin to deplete. By providing energy directly to muscle cells and contributing to gluconeogenesis, valine helps delay fatigue and reduce muscle protein breakdown during sustained physical effort. Together with leucine and isoleucine, valine supports muscle tissue recovery after exercise and contributes to maintaining the body's nitrogen balance.
Blood-brain barrier transport competition
Valine and the other branched-chain amino acids compete with tryptophan for the large neutral amino acid transporter (LAT1) that carries amino acids across the blood-brain barrier. Since tryptophan is the precursor to serotonin, the ratio of tryptophan to the competing large neutral amino acids (including valine) influences how much tryptophan reaches the brain and how much serotonin can be synthesized. This is one of the mechanisms through which high-protein meals — rich in competing amino acids — can affect serotonin-related mood and cognitive states.
Immune system regulation
Valine is required for the growth and maintenance of immune cells and contributes to the overall regulation of immune function. The immune system's demand for amino acids increases significantly during infection, illness, or injury, making adequate dietary valine important for maintaining immune competence under physiological stress.
Did You Know?
Sickle cell disease is caused by a single valine replacing a glutamic acid at position 6 of hemoglobin's beta chain. This one substitution — one amino acid in 287 — transforms how the protein behaves under low oxygen, changing the shape of millions of red blood cells and causing a serious systemic disease.
Interesting Facts
🌿
Named after valerian, found everywhere. Despite its name, valine has no special connection to valerian root — it is found in all protein-containing foods. Valerian is known for an entirely different set of compounds (valerenic acid and related molecules) responsible for its sedative properties. Valine simply happened to be isolated from casein while Fischer's lab was working with various protein sources.
🦠
Maple syrup urine disease. Like leucine and isoleucine, valine is one of the three amino acids whose accumulation causes maple syrup urine disease (MSUD) — a rare metabolic disorder where the enzyme that breaks down all three BCAAs is defective. The characteristic sweet odor of urine in MSUD comes from the keto-acid breakdown products of valine and the other two BCAAs accumulating to toxic levels.
⚙️
Strictly glucogenic. Unlike leucine (purely ketogenic) and isoleucine (both glucogenic and ketogenic), valine is strictly glucogenic — all its carbon atoms feed into succinyl-CoA, a citric acid cycle intermediate that generates glucose precursors. During starvation or prolonged exercise, valine contributes carbon to blood glucose maintenance through gluconeogenesis.
💉
Molecular medicine's founding moment. Vernon Ingram's 1956 identification of the valine substitution in sickle cell hemoglobin was the first proof that a genetic disease could be traced to a specific amino acid change in a specific protein. Before this, the connection between genes, proteins, and disease was largely theoretical. Sickle cell hemoglobin made it concrete — and changed medicine forever.
Where Valine Is Found
As an essential amino acid, valine must come from food. It is abundant in all complete protein sources. Values below are approximate per standard serving:
