The AtlasAmino acidsPolar, uncharged

ThreonineThr · T

An essential amino acid that the gut keeps most of for itself, built into the mucus that lines it, and whose main enzyme in other mammals is broken in us.

Status Reference · not yet an episodeSources 22Reviewed October 2026

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Skeletal formula — every corner and every line end is a carbon, and the hydrogens on carbon are left implied.

Molecule · Thr · 8 heavy atoms

Threonine

C₄H₉NO₃119.12 g/mol

An essential amino acid that the gut keeps most of for itself, built into the mucus that lines it, and whose main enzyme in other mammals is broken in us.

Built fromthe charted ones open their own entry

C4CarbonH9Hydrogen N Nitrogen O3Oxygen

Codes: Thr · T
Formula: C₄H₉NO₃
Molar mass: 119.12 g/mol
Systematic name: (2S,3R)-2-amino-3-hydroxybutanoic acid
Side chain: 1-Hydroxyethyl: a carbon carrying a hydroxyl and a methyl; polar and uncharged.
Class: Polar, uncharged
In the diet: Essential
Carbon skeleton: Glucogenic and ketogenic
pKa: α-COOH 2.11 · α-NH₃⁺ 9.62
Isoelectric point: pH 5.87
Hydropathy: -0.7 (Kyte–Doolittle)
Codons: ACU ACC ACA ACG

pKa and isoelectric point: Nelson and Cox, Lehninger Principles of Biochemistry, table of amino acid properties (free amino acid, 25 °C). Hydropathy: Kyte and Doolittle, J Mol Biol 1982. Essentiality: Reeds, J Nutr 2000. Formula and mass computed from the structure.

In brief

What it is

An essential amino acid with a small side chain carrying a hydroxyl group and a methyl group, which gives it a second stereocentre ¹. It is one of the three amino acids that are phosphorylated to switch proteins on and off ².

Why it matters

The gut takes most of it: in preterm infants 70 to 82% of dietary threonine was used by the intestine on first pass, largely to make mucins, the proteins of the mucus layer, whose cores are rich in threonine, serine and proline ^3,4.

Where it runs short

In rats on 30% of their threonine requirement for two weeks, mucin synthesis fell in the small and large intestine while other gut protein synthesis did not; at 60% there was no difference ⁵.

Where it turns

Threonine is a precursor of propionate, so it is restricted, along with methionine, valine and isoleucine, in methylmalonic and propionic acidaemia ⁶.

The intestine is first in line for threonine, and the first place a severe shortfall shows.

The molecule

Threonine is like serine with an extra methyl group: a two-carbon side chain with a hydroxyl on the first carbon. That hydroxyl is where sugars are attached in mucins and where kinases attach phosphate; a 2006 survey of signalling in human cells mapped 6,600 phosphorylation sites on 2,244 proteins ^2,4.

The extra methyl creates a second stereocentre on the side chain, so threonine and isoleucine are the two standard amino acids with two.

StereochemistryThreonine has two stereocentres, so it has four forms; the one in protein is (2S,3R). Its diastereomer, allo-threonine, is not used to build protein.

Charge · pHThreonine carries almost no net charge at the pH of blood.

Move across the chart to read the charge at any pH.

Computed from its pKa values (α-carboxyl 2.11, α-amino 9.62) by the Henderson–Hasselbalch equation, for the free amino acid in water at 25 °C. Inside a folded protein the same groups can shift by a unit or more. The faint lines are the other amino acids.

HydropathyThreonine scores -0.7: the 12th most water-loving of the twenty.

Kyte–Doolittle hydropathy index: positive values avoid water and tend to be buried inside a folded protein, negative values sit on its surface. Each letter is an amino acid; choose one to open it.

The genetic codeThreonine has 4 codons. The code is redundant, so most single-letter changes at the third position still write threonine.

The 64 codons of the standard genetic code. Codons for threonine are marked.
1st ↓ 2nd →	U	C	A	G	3rd
U	UUUPhe	UCUSer	UAUTyr	UGUCys	U
	UUCPhe	UCCSer	UACTyr	UGCCys	C
	UUALeu	UCASer	UAAStop	UGAStop	A
	UUGLeu	UCGSer	UAGStop	UGGTrp	G
C	CUULeu	CCUPro	CAUHis	CGUArg	U
	CUCLeu	CCCPro	CACHis	CGCArg	C
	CUALeu	CCAPro	CAAGln	CGAArg	A
	CUGLeu	CCGPro	CAGGln	CGGArg	G
A	AUUIle	ACUThr	AAUAsn	AGUSer	U
	AUCIle	ACCThr	AACAsn	AGCSer	C
	AUAIle	ACAThr	AAALys	AGAArg	A
	AUGMet	ACGThr	AAGLys	AGGArg	G
G	GUUVal	GCUAla	GAUAsp	GGUGly	U
	GUCVal	GCCAla	GACAsp	GGCGly	C
	GUAVal	GCAAla	GAAGlu	GGAGly	A
	GUGVal	GCGAla	GAGGlu	GGGGly	G

Where it comes from

Threonine is essential; the adult requirement is 15 mg per kilogram a day ¹. Microbes and plants make it as part of the aspartate family, alongside lysine, methionine and isoleucine ⁷.

EssentialMust come from food; the adult requirement is 15 mg per kilogram a day ¹.

How much

15 mg per kilogram a day for adults ¹.

Where it is in food

Any protein; whey glycomacropeptide is unusually rich in it ⁸.

In the bottle · fermentedOne of the three amino acids made in the largest amounts by fermentation, in engineered Escherichia coli or Corynebacterium glutamicum, for feed, food and medicine ^7,9.

What the body does with it

The intestine is threonine’s main consumer. In preterm infants on partial and full feeds, 82% and 70% of dietary threonine was taken up by the gut on first pass ³; in piglets the gut used 85 to 91%, mostly to build its own mucosal proteins ¹⁰.

Much of that goes into mucins. MUC2, the main gel-forming mucin of the intestine, has long domains rich in proline, threonine and serine that carry the dense sugar chains making up more than half its weight, and in mice the inner colonic mucus layer is renewed about every hour ⁴.

In mouse embryonic stem cells threonine has a role it does not have in us. These cells depend on threonine more than on any other amino acid, breaking it down by threonine dehydrogenase into glycine and acetyl-CoA to feed the methyl donor S-adenosylmethionine and maintain histone methylation ^11,12. The human version of the gene is an expressed pseudogene, truncated by a stop codon and a lost splice site in every person genotyped ¹³.

In three sentences each

Kept by the gut

Most dietary threonine never leaves the intestine: 70 to 82% in preterm infants and 85 to 91% in piglets, mainly built into the gut lining’s own proteins ^3,10.

The backbone of mucus

Mucins are more than half sugar by weight, attached to protein regions rich in proline, threonine and serine; the sugars hang from the hydroxyls of threonine and serine ⁴.

A broken enzyme in us

Mice break threonine down mostly by threonine dehydrogenase, which their embryonic stem cells depend on; in humans the gene is a pseudogene, and that route handled only 7 to 11% of threonine breakdown in adults ^11,13,14.

How it is made, moved and broken down

Because the human dehydrogenase is broken, threonine is mostly broken down by serine–threonine dehydratase, a vitamin B6 enzyme, to α-ketobutyrate and then propionyl-CoA ^14,15. Propionyl-CoA is where valine, isoleucine, methionine and odd-chain fats also meet, which is why threonine counts as a precursor in the propionate disorders ⁶.

Carbon skeleton · glucogenic and ketogenicMainly broken down by serine–threonine dehydratase to α-ketobutyrate and on to propionyl-CoA, which can make glucose; the minor dehydrogenase route yields glycine and acetyl-CoA ^11,14,15.

Breakdown in humansMainly by dehydration; the dehydrogenase route is minor in us ^14,15.

Threonine
Serine–threonine dehydrataseSDS · vitamin B6
α-Ketobutyrate
Branched-chain ketoacid dehydrogenaseBCKDHA · thiamine, lipoate
Propionyl-CoA

The route we lostWorking in mouse stem cells; a pseudogene in humans ^11,13.

Threonine
Threonine dehydrogenaseTDH (pseudogene) · NAD⁺
2-Amino-3-ketobutyrate
Glycine C-acetyltransferaseGCAT · vitamin B6
Glycine + acetyl-CoA

Where it matters most

Small and large intestine: Use most of the dietary supply, largely for mucins and mucosal proteins ^3,4,10.
Liver: Breaks down what remains, mainly by dehydration to α-ketobutyrate ^14,15.

When it goes wrong

Inherited

Methylmalonic and propionic acidaemia

MMUT, PCCA, PCCB · autosomal recessive

Threonine is one of the four amino acids whose breakdown feeds propionyl-CoA, so the diet restricts natural protein, and special amino acid mixtures free of those precursors are used ⁶.

How it is foundNewborn screening and plasma acylcarnitines, then organic acids ⁶.

Drug

Spasticity

In 26 people with multiple sclerosis, 7.5 g a day reduced signs of spasticity on examination without improving symptoms ¹⁶; a sequential trial in spinal spasticity found a modest effect ¹⁷. A Cochrane review of anti-spasticity agents made no recommendation ¹⁸.

Drug

ALS

Threonine and branched-chain amino acids were tried in motor neurone disease without benefit ¹⁹.

How it is measured

Plasma threonine is measured in the amino acid panel ²⁰. It has a niche use as an adherence marker in PKU, because glycomacropeptide, a whey protein used in low-phenylalanine formulas, contains two to three times more threonine than other proteins ⁸.

Plasma threoninePart of the amino acid panel ²⁰.In PKU, people using glycomacropeptide formulas, which are rich in threonine, had plasma threonine rise from about 103 to 149 µmol/L, and it is used to check adherence ⁸.Like the rest of the panel, it drifts with storage time and tube type ²⁰.

Food, supplements and the evidence

Establishedreplicated in people, for a named outcome

Threonine restriction, as part of precursor restriction, in methylmalonic and propionic acidaemia ⁶.

Uncertainsmall, short, mixed, surrogate or preclinical

Threonine for gut barrier health: the mucin effect is shown in animals at severe deficiency, not in people eating normal diets ^5,21.
Threonine for spasticity: small trials, modest signs, no symptomatic benefit ^16,17,18.

Sold asthe claim on the label, against the evidence

Nothing in this column.

What is strange about it

In humans, the gene for threonine’s main mammalian breakdown enzyme is still transcribed in every tissue, but it cannot make a working protein ¹³. Parasites such as trypanosomes have a working version, which makes it a possible drug target precisely because we lack it ²².

Threonine was tried in the 1990s for spasticity in multiple sclerosis and spinal disease; the trials found modest effects on examination without patients feeling better, and a Cochrane review made no recommendation ^16,17,18.

In mice, the inner mucus layer of the colon, built on threonine-rich mucin, is replaced about every hour ⁴.

Where it connects

In the Atlas

SerSerinePolar, uncharged GlyGlycineNonpolar, aliphatic MetMethionineNonpolar, aliphatic IleIsoleucineNonpolar, aliphatic ValValineNonpolar, aliphatic

Topics on the map

On the map

A star in The essential amino acids, one of 14. Gut mucus is unusually rich in it, and a large share of dietary threonine is used by the gut wall before the rest of the body sees any.

Find it on the map

Sources

22 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1
Joint WHO/FAO/UNU Expert Consultation. Protein and amino acid requirements in human nutrition.World Health Organ Tech Rep Ser · 2007 · (935):1–265PMID 18330140
Threonine, 15 mg/kg/day.
2
Olsen JV, Blagoev B, Gnad F, et al. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.Cell · 2006 · 127(3):635–648doi:10.1016/j.cell.2006.09.026 · PMID 17081983
6,600 phosphorylation sites on 2,244 proteins.
3
van der Schoor SRD, Wattimena DL, Huijmans J, et al. The gut takes nearly all: threonine kinetics in infants.Am J Clin Nutr · 2007 · 86(4):1132–1138doi:10.1093/ajcn/86.4.1132 · PMID 17921393
Eight preterm infants; first-pass gut uptake 82% and 70%.
4
Johansson MEV, Hansson GC. Immunological aspects of intestinal mucus and mucins.Nat Rev Immunol · 2016 · 16(10):639–649doi:10.1038/nri.2016.88 · PMID 27498766
Mucin structure; MUC2; renewal of the inner layer in mice.
5
Faure M, Moënnoz D, Montigon F, et al. Dietary threonine restriction specifically reduces intestinal mucin synthesis in rats.J Nutr · 2005 · 135(3):486–491doi:10.1093/jn/135.3.486 · PMID 15735082
Rats, two weeks; effect at 30% of requirement, not at 60%. Industry-funded.
6
Forny P, Hörster F, Ballhausen D, et al. Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: first revision.J Inherit Metab Dis · 2021 · 44(3):566–592doi:10.1002/jimd.12370 · PMID 33595124
Threonine among the propionate precursors.
7
Li Y, Wei H, Wang T, et al. Current status on metabolic engineering for the production of L-aspartate family amino acids and derivatives.Bioresour Technol · 2017 · 245(Pt B):1588–1602doi:10.1016/j.biortech.2017.05.145 · PMID 28579173
The aspartate family: lysine, methionine, threonine, isoleucine.
8
Ney DM, Stroup BM, Clayton MK, et al. Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial.Am J Clin Nutr · 2016 · 104(2):334–345doi:10.3945/ajcn.116.135293 · PMID 27413125
30 people; plasma threonine rose on glycomacropeptide.
9
Zhao G, Zhang D, Tang Y, et al. Recent advances on engineering Escherichia coli and Corynebacterium glutamicum for efficient production of L-threonine and its derivatives.Metab Eng · 2025 · 90:1–15doi:10.1016/j.ymben.2025.02.012 · PMID 40020772
One of the three major fermented amino acids.
10
Schaart MW, Schierbeek H, van der Schoor SRD, et al. Threonine utilization is high in the intestine of piglets.J Nutr · 2005 · 135(4):765–770doi:10.1093/jn/135.4.765 · PMID 15795432
Piglets; gut used 85–91% of dietary threonine.
11
Wang J, Alexander P, Wu L, et al. Dependence of mouse embryonic stem cells on threonine catabolism.Science · 2009 · 325(5939):435–439doi:10.1126/science.1173288 · PMID 19589965
Mouse cells; threonine dehydrogenase to glycine and acetyl-CoA.
12
Shyh-Chang N, Locasale JW, Lyssiotis CA, et al. Influence of threonine metabolism on S-adenosylmethionine and histone methylation.Science · 2013 · 339(6116):222–226doi:10.1126/science.1226603 · PMID 23118012
Mouse stem cells; threonine feeds SAM and H3K4 trimethylation.
13
Edgar AJ. The human L-threonine 3-dehydrogenase gene is an expressed pseudogene.BMC Genet · 2002 · 3:18doi:10.1186/1471-2156-3-18 · PMID 12361482
Truncated in all 23 people genotyped.
14
Darling PB, Grunow J, Rafii M, et al. Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans.Am J Physiol Endocrinol Metab · 2000 · 278(5):E877–E884doi:10.1152/ajpendo.2000.278.5.E877 · PMID 10780944
Six men; 7–11% of breakdown.
15
Tong H, Davis L. Cofactor identification of threonine-serine dehydratase from sheep liver.Protein Expr Purif · 1993 · 4(5):438–444doi:10.1006/prep.1993.1058 · PMID 8251757
Sheep enzyme: threonine to α-ketobutyrate; vitamin B6 cofactor.
16
Hauser SL, Doolittle TH, Lopez-Bresnahan M, et al. An antispasticity effect of threonine in multiple sclerosis.Arch Neurol · 1992 · 49(9):923–926doi:10.1001/archneur.1992.00530330045014 · PMID 1520082
26 patients, crossover, 7.5 g/day.
17
Lee A, Patterson V. A double-blind study of L-threonine in patients with spinal spasticity.Acta Neurol Scand · 1993 · 88(5):334–338doi:10.1111/j.1600-0404.1993.tb05353.x · PMID 8296531
6 g/day; sequential design, 33 patients.
18
Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis.Cochrane Database Syst Rev · 2003 · (4):CD001332doi:10.1002/14651858.CD001332 · PMID 14583932
No recommendation.
19
Parton M, Mitsumoto H, Leigh PN. Amino acids for amyotrophic lateral sclerosis/motor neuron disease.Cochrane Database Syst Rev · 2003 · (4):CD003457doi:10.1002/14651858.CD003457 · PMID 14583978
No benefit; review later withdrawn (2008).
20
Xia T, Gao S, Shu C, et al. Analysis of amino acids in human blood using UHPLC-MS/MS: potential interferences of storage time and vacutainer tube in pre-analytical procedure.Clin Biochem · 2016 · 49(18):1372–1378doi:10.1016/j.clinbiochem.2016.09.018 · PMID 27693603
Pre-analytical effects.
21
Nichols NL, Bertolo RF. Luminal threonine concentration acutely affects intestinal mucosal protein and mucin synthesis in piglets.J Nutr · 2008 · 138(7):1298–1303doi:10.1093/jn/138.7.1298 · PMID 18567751
Piglet gut loops; total mucosal protein synthesis also fell.
22
Adjogatse E, Erskine P, Wells SA, et al. Structure and function of L-threonine-3-dehydrogenase from the parasitic protozoan Trypanosoma brucei revealed by X-ray crystallography and geometric simulations.Acta Crystallogr D Struct Biol · 2018 · 74(Pt 9):861–876doi:10.1107/S2059798318009208 · PMID 30198897
The parasite enzyme as a drug target.

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