Discovery: The End of the Search
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 defined the nine essential amino acids for humans — a classification still used today.
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.
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.
Interesting Facts
Where Threonine Is Found
As an essential amino acid, threonine must come from food. It's found in good quantities in most complete proteins:
