The last of the 20 standard amino acids to be discovered — found in 1935, 129 years after asparagine opened the search. The closing chapter of a very long story.
Symbol
Thr · T
Discovered
1935
Mol. Weight
119.12 g/mol
Essential
Yes
T
Discovery: The End of the Search
L-Threonine
By 1930, biochemists believed they had identified all the amino acids that make up proteins. The list seemed complete. Then William Cumming Rose at the University of Illinois noticed something troubling: rats fed a diet of purified, known amino acids failed to grow normally. Something was missing.
Rose spent five painstaking years systematically analyzing protein hydrolysates, tracking down the unknown factor. In 1935, he isolated threonine from fibrin — a blood clot protein — and confirmed it as a new essential amino acid. It closed the book on 129 years of amino acid discovery that had begun when Vauquelin and Robiquet crystallized asparagine from asparagus juice in 1806. Threonine was the twentieth and final standard amino acid.
🔬 William Rose and Essential Amino Acids
Rose's discovery of threonine was part of a larger program: he was systematically determining which amino acids are essential for mammals. By feeding rats defined diets with and without each amino acid and measuring growth, he established the concept of essential versus non-essential amino acids on a rigorous experimental basis. His work in the 1930s and 1940s identified eight essential amino acids for humans — the ninth, histidine, was considered semi-essential at the time and formally added to the essential list in the WHO/FAO/UNU 2007 recommendations.
The amino acid that proved hardest to find was threonine precisely because it's present in proteins at relatively low levels and doesn't have a distinctive chemical feature that would make it stand out. Rose found it only by exhaustive exclusion — ruling out every other possibility until threonine was the only candidate left.
Identifiers and Properties of Threonine
Identity
IUPAC Name(2S,3R)-2-Amino-3-hydroxybutanoic acid
FormulaC₄H₉NO₃
Mol. Weight119.12 g/mol
CAS Number72-19-5
MDL NumberMFCD00064270
Chiral centers2
Physical
Melting point256 °C
Solubility90 g/L (20 °C)
pKa₁ (COOH)2.09
pKa₂ (NH₃⁺)9.10
pI5.60
Rf (BuOH/AcOH/H₂O = 12:3:5)0.35
Identifiers
Canonical SMILESCC(C(C(=O)O)N)O
Isomeric SMILESC[C@H]([C@@H](C(=O)O)N)O
InChIKeyAYFVYJQAPQTCCC-GBXIJKJYSA-N
CategoryPolar
EssentialYes
Two Chiral Centers — Like Isoleucine
Threonine shares with isoleucine the distinction of having two chiral centers — the alpha carbon and the beta carbon in its side chain. This means four stereoisomers exist in principle. Nature uses only one: L-threonine, specifically (2S,3R)-threonine. The other three forms — D-threonine, L-allothreonine, and D-allothreonine — are not found in standard proteins.
The beta-hydroxyl group — a –CHOH– in the side chain — is what creates the second chiral center. That same hydroxyl group is also threonine's most chemically important feature: it can be phosphorylated (making threonine one of the three main phosphorylation targets alongside serine and tyrosine), and it participates in O-linked glycosylation.
Threonine in the Gut: Mucin Production
Threonine has a particularly important role in the intestine. Mucins — the heavily glycosylated proteins that form the protective mucus layer lining the gut — are exceptionally rich in threonine. The intestinal epithelium, which constantly renews itself and produces new mucin, is one of the highest consumers of dietary threonine in the body. When threonine intake is insufficient, mucin production falls and the integrity of the gut's protective lining is compromised.
Functions and Benefits of L-Threonine
As an essential amino acid, threonine must be obtained from food and supports a wide range of physiological processes.
Glycine and serine synthesis — collagen and elastin
Threonine is a metabolic precursor for glycine — via threonine aldolase, which cleaves threonine into glycine and acetaldehyde. Glycine is in turn required for the synthesis of collagen, elastin, and muscle proteins. This makes threonine indirectly important for connective tissue integrity, skin elasticity, and muscle maintenance. It also supports the formation of bone matrix and tooth enamel, both of which depend on collagen scaffolding.
Liver fat metabolism
Threonine, in combination with methionine and aspartate, contributes to the proper metabolism of fats in the liver. These amino acids participate in lipotropic processes — helping the liver process and export fats rather than allowing them to accumulate. Impaired threonine availability may contribute to conditions associated with hepatic fat deposition.
Immune function and thymus support
Threonine supports immune function in multiple ways. It is required for the synthesis of antibodies and immunoglobulins. It also promotes growth and activity of the thymus gland — the organ in which T-lymphocytes mature — making adequate threonine supply important for both humoral and cell-mediated immunity. Recovery from surgery and trauma, which places high demands on protein synthesis and immune function, benefits from adequate threonine intake.
Central nervous system and neuromuscular conditions
Threonine is found in elevated concentrations in the central nervous system and plays a role in spinal cord function. It is a precursor to glycine, which acts as an inhibitory neurotransmitter in the spinal cord. Clinical research has investigated threonine supplementation for the treatment of spasticity in ALS (amyotrophic lateral sclerosis) and multiple sclerosis, where glycine deficiency in the spinal cord is thought to contribute to increased muscle rigidity. Results have shown modest benefits in some studies, though threonine is not an established treatment for either condition.
Did You Know?
William Rose, who discovered threonine in 1935, also established the concept of essential amino acids through rat-feeding experiments. He determined which amino acids humans cannot synthesize — a list still used in nutrition science today.
Interesting Facts
🏁
The last one found. The 129-year gap between the discovery of asparagine (1806) and threonine (1935) represents the entire history of amino acid chemistry. Every other standard amino acid was identified in between. Threonine's discovery closed one of the longest running open questions in biochemistry.
💊
Target of an important antibiotic. The antibiotic borrelidin inhibits threonyl-tRNA synthetase — the enzyme that attaches threonine to its transfer RNA during protein synthesis. By blocking threonine incorporation into proteins, borrelidin halts bacterial growth. It's one of several antibiotics that work by targeting the enzymes responsible for specific amino acid charging, demonstrating that every step of protein synthesis is a potential drug target.
🧬
Phosphorylation hotspot. Like serine, threonine is a major target for protein kinases. Threonine phosphorylation is particularly important in cell cycle regulation: the enzyme CDK1 (cyclin-dependent kinase 1), which drives cells into mitosis, phosphorylates specific threonine residues on multiple target proteins. Disrupting these phosphorylation events stops the cell cycle — a mechanism exploited by several cancer drugs.
🌱
Limiting amino acid in some diets. In plant-based diets dominated by cereals, threonine can become a limiting amino acid alongside lysine. Legumes (beans, lentils) are good threonine sources. The pattern of threonine deficiency in grain-heavy diets was one reason why Rose's experiments — showing that rats failed to grow without it — had immediate practical implications for human nutrition.
Where Threonine Is Found
As an essential amino acid, threonine must come from food. It is found in good quantities in most complete proteins. Values below are approximate per standard serving:
