An official website of the United States government

Threonine

PubChem CID
6288
Structure
Threonine_small.png
Threonine_3D_Structure.png
Threonine__Crystal_Structure.png
Molecular Formula
Synonyms
  • L-threonine
  • threonine
  • 72-19-5
  • (2S,3R)-2-amino-3-hydroxybutanoic acid
  • DL-Threonine
Molecular Weight
119.12 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
L-threonine is an optically active form of threonine having L-configuration. It has a role as a nutraceutical, a micronutrient, a Saccharomyces cerevisiae metabolite, a plant metabolite, an Escherichia coli metabolite, a human metabolite, an algal metabolite and a mouse metabolite. It is an aspartate family amino acid, a proteinogenic amino acid, a threonine and a L-alpha-amino acid. It is a conjugate base of a L-threoninium. It is a conjugate acid of a L-threoninate. It is an enantiomer of a D-threonine. It is a tautomer of a L-threonine zwitterion.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
L-Threonine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
See also: Amlisimod (monomer of) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Threonine.png

1.2 3D Conformer

1.3 Crystal Structures

CCDC Number
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Biologic Description

SVG Image
SVG Image
IUPAC Condensed
H-Thr-OH
Sequence
T
PLN
H-T-OH
HELM
PEPTIDE1{T}$$$$
IUPAC
L-threonine

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

(2S,3R)-2-amino-3-hydroxybutanoic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

3.1.2 InChI

InChI=1S/C4H9NO3/c1-2(6)3(5)4(7)8/h2-3,6H,5H2,1H3,(H,7,8)/t2-,3+/m1/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.3 InChIKey

AYFVYJQAPQTCCC-GBXIJSLDSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.4 SMILES

C[C@H]([C@@H](C(=O)O)N)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

3.2 Molecular Formula

C4H9NO3
Computed by PubChem 2.2 (PubChem release 2021.10.14)

3.3 Other Identifiers

3.3.1 CAS

80-68-2
72-19-5
7013-32-3

3.3.3 Deprecated CAS

1043597-96-1, 13095-55-1, 1370710-06-7, 154605-64-8, 154605-68-2, 1644578-86-8, 25275-17-6, 36676-50-3
1187422-62-3, 31138-27-9, 5090-44-8
1043597-96-1, 13095-55-1, 1370710-06-7, 154605-64-8, 154605-68-2, 1644578-86-8, 25275-17-6, 7004-04-8

3.3.4 European Community (EC) Number

3.3.5 UNII

3.3.6 ChEBI ID

3.3.7 ChEMBL ID

3.3.8 DrugBank ID

3.3.9 DSSTox Substance ID

3.3.10 FEMA Number

3.3.11 HMDB ID

3.3.12 JECFA Number

2119

3.3.13 KEGG ID

3.3.14 Metabolomics Workbench ID

3.3.15 NCI Thesaurus Code

3.3.16 Nikkaji Number

3.3.17 NSC Number

3.3.18 PharmGKB ID

3.3.19 RXCUI

3.3.20 Wikidata

3.3.21 Wikipedia

3.4 Synonyms

3.4.1 MeSH Entry Terms

  • L Threonine
  • L-Threonine
  • Threonine

3.4.2 Depositor-Supplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name
Molecular Weight
Property Value
119.12 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-2.9
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
119.058243149 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
119.058243149 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
83.6 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
8
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
93.3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
2
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

4.2 Experimental Properties

4.2.1 Physical Description

Solid; [Merck Index]
Hemihydrate: Solid; [Merck Index] White powder; [Sigma-Aldrich MSDS]
Solid
White crystalline powder; slight savoury aroma

4.2.2 Color / Form

Colorless crystals
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 1241
Crystals
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1611

4.2.3 Melting Point

256 dec °C
PhysProp
256 °C (decomposes)
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-486
MP: 228-229 °C with decomposition (dl-threonine); 255-275 °C with decomposition (l(-)-threonine) (naturally occurring); 250-252 °C (dl-allo-threonine)
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 1241
256 °C

4.2.4 Solubility

97000 mg/L (at 25 °C)
YALKOWSKY,SH & DANNENFELSER,RM (1992)
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-486
Insoluble in common neutral solvents
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1611
In water, 9.70X10+4 mg/L at 25 °C
Yalkowsky, S.H., He, Yan., Handbook of Aqueous Solubility Data: An Extensive Compilation of Aqueous Solubility Data for Organic Compounds Extracted from the AQUASOL dATAbASE. CRC Press LLC, Boca Raton, FL. 2003., p. 124
97.0 mg/mL
Sparingly soluble in water; Soluble in buffer systems pH 5.5
Practically insoluble (in ethanol)

4.2.5 Vapor Pressure

0.00000004 [mmHg]

4.2.6 LogP

-2.94
HANSCH,C ET AL. (1995)
log Kow = -2.94
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 10
-2.94
HANSCH,C ET AL. (1995)

4.2.7 LogS

-0.09
ADME Research, USCD

4.2.8 Decomposition

When heated to decomposition it emits toxic fumes of /nitric oxide/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3460

4.2.9 Ionization Efficiency

1 of 2
Ionization mode
Positive
logIE
2.35
pH
2.7
Instrument
Agilent XCT
Ion source
Electrospray ionization
Additive
formic acid (5.3nM)
Organic modifier
MeCN (80%)
2 of 2
Ionization mode
Negative
logIE
-0.52
pH
10.5
Instrument
Agilent XCT
Ion source
Electrospray ionization
Additive
ammonia (10nM)
Organic modifier
MeCN (80%)

4.2.10 Dissociation Constants

pKa
5.60
pKa1' = 2.63 (SRC: carboxylic acid); pKa2' = 10.43 (SRC: amine)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1611

4.2.11 Collision Cross Section

120.2 Ų [M-H]- [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

126.7 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

122 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine]
141.36 Ų [M-H]- [CCS Type: DT; Method: stepped-field]

129.2 Ų [M-H]-

127.3 Ų [M+H]+

S50 | CCSCOMPEND | The Unified Collision Cross Section (CCS) Compendium | DOI:10.5281/zenodo.2658162

4.2.12 Other Experimental Properties

Orthorhombic crystals, decomposes at 229-230 °C /Threonine, DL-form hemihydrate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1611
UV: 1-34 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /Threonine (DL)/
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V5: 5103

4.3 Chemical Classes

Biological Agents -> Amino Acids and Derivatives

4.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749

4.3.2 Cosmetics

Cosmetic ingredients (Threonine) -> CIR (Cosmetic Ingredient Review)
Hair conditioning; Antistatic
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

4.3.3 Food Additives

FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, NUTRIENT SUPPLEMENT -> FDA Substance added to food

5 Spectral Information

5.1 1D NMR Spectra

1D NMR Spectra
1H NMR: 8212 (Sadtler Research Laboratories spectral collection) /Threonine (DL)/
1D NMR Spectra
1H NMR: 11978 (Sadtler Research Laboratories spectral collection)

5.1.1 1H NMR Spectra

1 of 4
View All
Spectra ID
Instrument Type
Varian
Frequency
500 MHz
Solvent
Water
pH
7.00
Shifts [ppm]:Intensity
4.25:11.71, 1.32:100.00, 3.57:37.23, 4.24:11.46, 4.26:10.09, 1.31:99.55, 3.58:38.22, 4.27:3.05, 4.23:10.46, 4.22:3.17
Thumbnail
Thumbnail
2 of 4
View All
Spectra ID
Instrument Type
Bruker
Solvent
D2O
pH
7.4
Shifts [ppm]:Intensity
4.25:1.42, 3.58:3.73, 4.22:0.44, 1.31:14.74, 3.57:3.69, 4.24:1.63, 4.24:1.48, 4.23:1.40, 1.32:14.73, 4.26:0.41
Thumbnail
Thumbnail

5.1.2 13C NMR Spectra

1 of 5
View All
13C NMR Spectra
13C NMR: 87 (Johnson and Jankowski, Carbon-13 NMR Spectra, John Wiley & Sons, New York) /Threonine (DL)/
2 of 5
View All
Spectra ID
Instrument Type
Bruker
Frequency
125 MHz
Solvent
Water
pH
7.00
Shifts [ppm]:Intensity
63.27:77.15, 175.68:28.22, -0.00:11.74, 22.17:83.18, 68.74:80.15
Thumbnail
Thumbnail

5.2 2D NMR Spectra

5.2.1 1H-1H NMR Spectra

2D NMR Spectra Type
1H-1H TOCSY
Spectra ID
Shifts [ppm] (F2:F1)
3.58:1.33, 4.25:4.24, 4.25:1.31, 4.25:3.58, 4.25:1.33, 1.62:1.30, 1.32:1.31, 1.32:1.33, 4.25:4.23, 3.58:3.58, 3.58:1.31, 1.32:4.24, 3.58:4.24, 1.32:3.58
Thumbnail
Thumbnail

5.2.2 1H-13C NMR Spectra

2D NMR Spectra Type
1H-13C HSQC
Spectra ID
Instrument Type
Bruker
Frequency
400 MHz
Solvent
Water
pH
7.00
Shifts [ppm] (F2:F1):Intensity
4.24:68.91:0.48, 1.32:22.30:1.00, 3.57:63.46:0.74
Thumbnail
Thumbnail

5.3 Mass Spectrometry

5.3.1 GC-MS

1 of 14
View All
Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

117.0 1

130.0 0.69

219.0 0.30

146.0 0.27

131.0 0.23

Thumbnail
Thumbnail
2 of 14
View All
Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

117.0 1

218.0 0.94

219.0 0.88

101.0 0.62

100.0 0.34

Thumbnail
Thumbnail

5.3.2 MS-MS

1 of 6
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

56.04914 100

74.05986 24.90

57.03327 10.40

46.02834 3.30

Thumbnail
Thumbnail
2 of 6
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

74.06075 100

56.05042 34.66

102.05549 33.99

120.08085 13.30

84.04479 4.67

Thumbnail
Thumbnail

5.3.3 LC-MS

1 of 3
View All
MoNA ID
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
118
Instrument
API 2000
Instrument Type
QqQ
Ionization
ESI
Ionization Mode
negative
Collision Energy
-12
Top 5 Peaks
74 100
Thumbnail
Thumbnail
2 of 3
View All
MoNA ID
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
118.05044
Instrument
Q-Tof Premier, Waters
Instrument Type
LC-Q-TOF/MS
Ionization
ESI
Ionization Mode
negative
Collision Energy
Ramp 5-45 V
Top 5 Peaks

74.0258 51.39

118.0504 33.70

Thumbnail
Thumbnail

5.3.4 Other MS

1 of 4
View All
Other MS
MASS: 60 (Aldermaston, Eight Peak Index of Mass Spectra, U.K.) /Threonine (DL)/
Other MS
MASS: 60 (Aldermaston, Eight Peak Index of Mass Spectra, U.K.) /Threonine (D)/
Other MS
MASS: 26149 (NIST/EPA/MSDC Mass Spectral Database, 1990 version)
2 of 4
View All
MoNA ID
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
120.08
Instrument
TQD, Waters
Instrument Type
Flow-injection QqQ/MS
Ionization
ESI
Ionization Mode
positive
Collision Energy
30
Top 5 Peaks

56 100

74 17.60

55 13.48

28 12.19

29 9.32

Thumbnail
Thumbnail

5.4 IR Spectra

IR Spectra
IR: 21020 (Coblentz Society Spectral Collection) /Threonine (DL)/
IR Spectra
IR: 18771 (Coblentz Society Spectral Collection) /Threonine (D)/
IR Spectra
IR: 21317 (Sadtler Research Laboratories IR grating collection)

5.4.1 FTIR Spectra

1 of 2
Technique
KBr WAFER
Source of Sample
E. MERCK AG, DARMSTADT, GERMANY
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Technique
Mull
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Aldrich
Catalog Number
T34207
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail

5.4.2 ATR-IR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
National Biochemicals Corporation
Lot Number
5617
Copyright
Copyright © 2014-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Source of Sample
Aldrich
Catalog Number
T34207
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail

5.5 Raman Spectra

1 of 3
View All
Raman Spectra
Raman: 423 (Sadtler Research Laboratories spectral collection)
2 of 3
View All
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Spectrum Chemical Manufacturing Corp.
Catalog Number
T1056
Lot Number
XX0202
Copyright
Copyright © 2015-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail

5.6 Other Spectra

Optically active
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 1241

7 Chemical Vendors

8 Drug and Medication Information

8.1 Drug Indication

L-Threonine makes up collagen, elastin, and enamel protein. It aids proper fat metabolism in the liver, helps the digestive and intestinal tracts function more smoothly, and assists in metabolism and assimilation.

8.2 FDA National Drug Code Directory

8.3 Drug Labels

Active ingredient and drug
Homeopathic product and label

8.4 Therapeutic Uses

L-threonine has been used clinically with the aim of increasing glycine concentrations in the cerebral spinal fluid of patients with spasticity. When given in amounts of 4.5 to 6.0 g/day for 14 days, no adverse clinical effects were noted in such patients.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 731, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/Experimental Therapy/ To determine whether the naturally occurring amino acid threonine, a potential precursor for glycine biosynthesis in the spinal cord, has an effect on spasticity in multiple sclerosis, 26 ambulatory patients were entered into a randomized crossover trial. Threonine administered at a total daily dose of 7.5 g reduced signs of spasticity on clinical examination, although no symptomatic improvement could be detected by the examining physician or the patient. In contrast to the side effects of sedation and increased motor weakness associated with antispasticity drugs commonly used for the treatment of multiple sclerosis, no side effects or toxic effects of threonine were identified...
Hauser SL et al; Arch Neurol 49 (9): 923-6 (1992).
/Experimental Therapy/ ... 4.5 and 6.0 g/day of L-threonine /was administered/ to 18 patients with familial spastic paraparesis (FSP) according to a double-blind, crossover protocol. ... L-threonine significantly suppressed the signs of spasticity even though the benefits were not clinically valuable.
Growdon JH et al; Clin Neuropharmacol 14 (5): 403-12 (1991).
/Experimental Therapy/ A randomized, double-blind, placebo-controlled trial was carried out in 22 patients with hypostatic leg ulceration. Patients were treated topically with either a cream containing the amino acids l-cysteine, glycine and dl-threonine or the cream base alone (placebo). Most patients had their leg ulcers treated and dressed 3-times per week for 12 weeks. ... The degree of healing and decrease of pain were significantly better in the group of patients receiving the amino acid combination. It would appear from this study that l-cysteine, glycine and dl-threonine in combination are of value in promoting would healing in hypostatic leg ulceration.
Harvey SG et al; Pharmatherapeutica 4 (4): 227-30 (1985).

8.5 Drug Warnings

... In this placebo-controlled crossover study, the effect of supplemental oral threonine (THR) on the plasma amino acid concentrations of 12 patients with hyperphenylalaninemia was investigated. Before starting the first treatment period of this cross-over study, the patients were randomly assigned to one of two groups supplemented either with approximately 50 mg THR/kg per day or with a similar amount of maltodextrin as placebo. After a feeding period of 8 weeks and a wash-out period of 8 weeks, the supplements were crossed over and the study continued for an additional 8 weeks. Blood was obtained at the start and the end of each supplementation period. Dietary THR supplementation of approximately 50 mg/kg per day resulted in a significant decrease of plasma phenylalanine (PHE) levels ( P = 0.0234). There was a close positive correlation between plasma and urinary PHE concentrations ( P < 0.001) indicating that the lower plasma PHE levels in the THR supplemented patients were not caused by higher urinary excretion of PHE. CONCLUSIONS: The data of the present study show that oral THR supplementation has a clear plasma-PHE-reducing effect but they do not allow any conclusion about the mechanisms responsible for the observed effect. Although it seems attractive on the basis of the present data to use THR supplementation in patients with hyperphenylalaninemia, the mechanism of the observed effect should be clarified before introduction of such a treatment in these patients.
Sanjurjo P et al; J Pediatr Gastroenterol Nutr 36 (1): 23-6 (2003).
A two center, double-blind, placebo-controlled treatment trial with oral branched chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 8 g, and L-valine 6.4 g daily) or L-threonine (4 g daily) with pyridoxal phosphate (160 mg daily) /was conducted/ for six months in patients with amyotrophic lateral sclerosis (ALS). ... The amino acids were well tolerated. The results of our study failed to show a beneficial effect of BCAA or L-threonine treatment for six months on the disease course in ALS. The higher rate of loss of pulmonary function in patients treated with BCAA or L-threonine may have been due to chance, but an adverse effect of these amino acids cannot be ruled out.
Tandan R et al; Neurology 47 (5): 1220-6 (1996).
The threonine content of most of the infant formulas currently on the market is approximately 20% higher than the threonine concentration in human milk. Due to this high threonine content the plasma threonine concentrations are up to twice as high in premature infants fed these formulas than in infants fed human milk. Increasing the threonine in plasma leads to increasing brain glycine and thereby affects the neurotransmitter balance in the brain. This may have consequences for brain development during early postnatal life. Therefore, excessive threonine intake during infant feeding should be avoided.
Boehm G et al; Pediatr Res 44 (6): 900-6 (1998).

8.6 Biomarker Information

9 Food Additives and Ingredients

9.1 Food Additive Classes

Flavoring Agents
JECFA Functional Classes
Flavouring Agent -> FLAVOURING_AGENT;

9.2 FEMA Flavor Profile

Savory, Pleasant

9.3 FDA Substances Added to Food

Substance
Used for (Technical Effect)
FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, NUTRIENT SUPPLEMENT
Document Number (21 eCFR)
FEMA Number
4710
GRAS Number
25
JECFA Flavor Number
2119

9.4 Evaluations of the Joint FAO / WHO Expert Committee on Food Additives - JECFA

Chemical Name
L-THREONINE
Evaluation Year
2012
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph

10 Pharmacology and Biochemistry

10.1 Pharmacodynamics

L-Threonine is an essential amino acid that helps to maintain the proper protein balance in the body. It is important for the formation of collagen, elastin, and tooth enamel, and aids liver and lipotropic function when combined with aspartic acid and methionine.

10.2 Bionecessity

An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
Table: Comparison of the Pool Sizes of Free and Protein-Bound Amino Acids in Rat Muscle
Indispensable amino acids
Histidine
Protein (umol/g Wet Weight)
26
Free (umol/g Wet Weight)
0.39
Protein Free Ratio (umol/g Wet Weight)
67
Indispensable amino acids
Isoleucine
Protein (umol/g Wet Weight)
50
Free (umol/g Wet Weight)
0.16
Protein Free Ratio (umol/g Wet Weight)
306
Indispensable amino acids
Leucine
Protein (umol/g Wet Weight)
109
Free (umol/g Wet Weight)
0.20
Protein Free Ratio (umol/g Wet Weight)
556
Indispensable amino acids
Lysine
Protein (umol/g Wet Weight)
58
Free (umol/g Wet Weight)
1.86
Protein Free Ratio (umol/g Wet Weight)
31
Indispensable amino acids
Methionine
Protein (umol/g Wet Weight)
36
Free (umol/g Wet Weight)
0.16
Protein Free Ratio (umol/g Wet Weight)
225
Indispensable amino acids
Phenylalanine
Protein (umol/g Wet Weight)
45
Free (umol/g Wet Weight)
0.07
Protein Free Ratio (umol/g Wet Weight)
646
Indispensable amino acids
Threonine
Protein (umol/g Wet Weight)
60
Free (umol/g Wet Weight)
1.94
Protein Free Ratio (umol/g Wet Weight)
31
Indispensable amino acids
Valine
Protein (umol/g Wet Weight)
83
Free (umol/g Wet Weight)
0.31
Protein Free Ratio (umol/g Wet Weight)
272
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 597, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
An experimental formula based on acid whey without GMP and a formula based on sweet whey with rich glycomacropeptide(GMP) (threonine content 17.2% higher than in the experimental formula) but otherwise with identical composition were tested with particular respect to threonine metabolism. Fourteen preterm infants appropriate for gestational age were enrolled in this randomized cross-over study. After a feeding period of at least 7 days, the nutrition of each infant was switched to the other formula for the second feeding period. At the end of each feeding period, the concentrations of creatinine and amino acids in the plasma and in the urine were measured. In the plasma, the threonine concentration was significantly lower in the group fed the experimental GMP-free formula than in the group fed the sweet whey formula (P < 0.001). Renal excretion of all essential amino acids was generally very low and less than 2% of the intake, indicating that the kidneys had no marked homeostatic function with respect to plasma amino acid. The plasma concentrations of the threonine metabolites glycine and serine, and that of urea were not influenced by diet. Feeding a whey protein-predominant bovine milk produced from acid whey protein reduces significantly the hyperthreoninemia commonly found in formula-fed preterm infants. Thus, acid whey formulas should be recommended for feeding preterm infants.
Rigo J et al; J Pediatr Gastroenterol Nutr 32 (2): 127-30 (2001). Erratum in: J Pediatr Gastroenterol Nutr 32 (5): 620 (2001).
Calculation of Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) for Threonine for Children Ages 7 Months Through 18 Years
Age and Gender
7-12 months, Boys, Girls
Maintenance (mg/kg/day)
16
Amino Acid Deposition (mg/kg/day)
10
Total = EAR (mg/kg/day)
34
RDA (mg/kg/day)
49
Age and Gender
1-3 years, Boys, Girls
Maintenance (mg/kg/day)
16
Amino Acid Deposition (mg/kg/day)
5
Total = EAR (mg/kg/day)
24
RDA (mg/kg/day)
32
Age and Gender
4-8 years, Boys, Girls
Maintenance (mg/kg/day)
16
Amino Acid Deposition (mg/kg/day)
2
Total = EAR (mg/kg/day)
19
RDA (mg/kg/day)
24
Age and Gender
9-13 years, Boys
Maintenance (mg/kg/day)
16
Amino Acid Deposition (mg/kg/day)
2
Total = EAR (mg/kg/day)
19
RDA (mg/kg/day)
24
Age and Gender
9-13 years, Girls
Maintenance (mg/kg/day)
16
Amino Acid Deposition (mg/kg/day)
1
Total = EAR (mg/kg/day)
18
RDA (mg/kg/day)
22
Age and Gender
14-18 years, Boys
Maintenance (mg/kg/day)
16
Amino Acid Deposition (mg/kg/day)
1
Total = EAR (mg/kg/day)
18
RDA (mg/kg/day)
22
Age and Gender
14-18 years, Girls
Maintenance (mg/kg/day)
16
Amino Acid Deposition (mg/kg/day)
<0.5
Total = EAR (mg/kg/day)
17
RDA (mg/kg/day)
21
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 672-679, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
For more Bionecessity (Complete) data for L-Threonine (22 total), please visit the HSDB record page.

10.3 Absorption, Distribution and Excretion

Although the free amino acids dissolved in the body fluids are only a very small proportion of the body's total mass of amino acids, they are very important for the nutritional and metabolic control of the body's proteins. ... Although the plasma compartment is most easily sampled, the concentration of most amino acids is higher in tissue intracellular pools. Typically, large neutral amino acids, such as leucine and phenylalanine, are essentially in equilibrium with the plasma. Others, notably glutamine, glutamic acid, and glycine, are 10- to 50-fold more concentrated in the intracellular pool. Dietary variations or pathological conditions can result in substantial changes in the concentrations of the individual free amino acids in both the plasma and tissue pools. /Amino acids/
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 596, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
After ingestion, proteins are denatured by the acid in the stomach, where they are also cleaved into smaller peptides by the enzyme pepsin, which is activated by the increase in stomach acidity that occurs on feeding. The proteins and peptides then pass into the small intestine, where the peptide bonds are hydrolyzed by a variety of enzymes. These bond-specific enzymes originate in the pancreas and include trypsin, chymotrypsins, elastase, and carboxypeptidases. The resultant mixture of free amino acids and small peptides is then transported into the mucosal cells by a number of carrier systems for specific amino acids and for di- and tri-peptides, each specific for a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are then secreted into the portal blood by other specific carrier systems in the mucosal cell or are further metabolized within the cell itself. Absorbed amino acids pass into the liver, where a portion of the amino acids are taken up and used; the remainder pass through into the systemic circulation and are utilized by the peripheral tissues. /Amino acids/
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 599, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
About 11 to 15 g of nitrogen are excreted each day in the urine of a healthy adult consuming 70 to 100 g of protein, mostly in the form of urea, with smaller contributions from ammonia, uric acid, creatinine, and some free amino acids. These are the end products of protein metabolism, with urea and ammonia arising from the partial oxidation of amino acids. Uric acid and creatinine are indirectly derived from amino acids as well. The removal of nitrogen from the individual amino acids and its conversion to a form that can be excreted by the kidney can be considered as a two-part process. The first step usually takes place by one of two types of enzymatic reactions: transamination or deamination. Transamination is a reversible reaction that uses ketoacid intermediates of glucose metabolism (e.g., pyruvate, oxaloacetate, and alpha-ketoglutarate) as recipients of the amino nitrogen. Most amino acids can take part in these reactions, with the result that their amino nitrogen is transferred to just three amino acids: alanine from pyruvate, aspartate from oxaloacetate, and glutamate from alpha-ketoglutarate. Unlike many amino acids, branched-chain amino acid transamination occurs throughout the body, particularly in skeletal muscle. Here the main recipients of amino nitrogen are alanine and glutamine (from pyruvate and glutamate, respectively), which then pass into the circulation. These serve as important carriers of nitrogen from the periphery (skeletal muscle) to the intestine and liver. In the small intestine, glutamine is extracted and metabolized to ammonia, alanine, and citrulline, which are then conveyed to the liver via the portal circulation. Nitrogen is also removed from amino acids by deamination reactions, which result in the formation of ammonia. A number of amino acids can be deaminated, either directly (histidine), by dehydration (serine, threonine), by way of the purine nucleotide cycle (aspartate), or by oxidative deamination (glutamate). ... Glutamate is also formed in the specific degradation pathways of arginine and lysine. Thus, nitrogen from any amino acid can be funneled into the two precursors of urea synthesis, ammonia and aspartate.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 603-604, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
Although it seems clear that the efficiency of dietary protein digestion (in the sense of removal of amino acids from the small intestinal lumen) is high, there is now good evidence to show that nutritionally significant quantities of indispensable amino acids are metabolized by the tissues of the splanchnic bed, including the mucosal cells of the intestine. Thus, less than 100% of the amino acids removed from the intestinal lumen appear in the peripheral circulation, and the quantities that are metabolized by the splanchnic bed vary among the amino acids, with intestinal threonine metabolism being particularly high.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 600, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
For more Absorption, Distribution and Excretion (Complete) data for L-Threonine (12 total), please visit the HSDB record page.

10.4 Metabolism / Metabolites

Hepatic
The evidence indicates that excess threonine is converted to carbohydrate, liver lipids, and carbon dioxide.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 730, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
L-Threonine is a large neutral amino acid that is indispensable. ... L-threonine does not take part in transamination reactions.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 730, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
Once the amino acid deamination products enter the tricarboxylic acid (TCA) cycle (also known as the citric acid cycle or Krebs cycle) or the glycolytic pathway, their carbon skeletons are also available for use in biosynthetic pathways, particularly for glucose and fat. Whether glucose or fat is formed from the carbon skeleton of an amino acid depends on its point of entry into these two pathways. If they enter as acetyl-CoA, then only fat or ketone bodies can be formed. The carbon skeletons of other amino acids can, however, enter the pathways in such a way that their carbons can be used for gluconeogenesis. This is the basis for the classical nutritional description of amino acids as either ketogenic or glucogenic (ie, able to give rise to either ketones [or fat] or glucose). Some amino acids produce both products upon degradation and so are considered both ketogenic and glucogenic.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 606, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
The threonine dehydrogenase (TDG) pathway is a significant route of threonine degradation, yielding glycine in experimental animals, but has not been accurately quantitated in humans. Therefore, the effect of a large excess of dietary threonine, given either as free amino acid (+Thr) or as a constituent of protein (+P-Thr), on threonine catabolism to CO(2) and to glycine was studied in six healthy adult males using a 4-h constant infusion of L-[1-(13)C]threonine and [(15)N]glycine. Gas chromatography-combustion isotope ratio mass spectrometry was used to determine [(13)C]glycine produced from labeled threonine. Threonine intakes were higher on +Thr and +P-Thr diets compared with control (126, 126, and 50 micromol x kg(-1) x h(-1), SD 8, P < 0.0001). Threonine oxidation to CO(2) increased threefold in subjects on +Thr and +P-Thr vs. control (49, 45, and 15 micromol x kg(-1) x h(-1), SD 6, P < 0.0001). Threonine conversion to glycine tended to be higher on +Thr and +P-Thr vs. control (3.5, 3.4, and 1.6 micromol x kg(-1) x h(-1), SD 1.3, P = 0.06). The TDG pathway accounted for only 7-11% of total threonine catabolism and therefore is a minor pathway in the human adult.
Darling PB et al; Am J Physiol Endocrinol Metab 278 (5): E877-84 (2000).
For more Metabolism/Metabolites (Complete) data for L-Threonine (8 total), please visit the HSDB record page.

10.5 Mechanism of Action

L-Threonine is a precursor to the amino acids glycine and serine. It acts as a lipotropic in controlling fat build-up in the liver. May help combat mental illness and may be very useful in indigestion and intestinal malfunctions. Also, threonine prevents excessive liver fat. Nutrients are more readily absorbed when threonine is present.
Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Protein synthesis/
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 601-602, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome. /Protein degradation/
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 602, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html

10.6 Human Metabolite Information

10.6.1 Tissue Locations

  • All Tissues
  • Placenta
  • Prostate

10.6.2 Cellular Locations

  • Cytoplasm
  • Extracellular

10.6.3 Metabolite Pathways

10.7 Biochemical Reactions

10.8 Transformations

11 Use and Manufacturing

11.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: Threonine
EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
Sources/Uses
An essential amino acid; [Merck Index] Used as a flavoring agent and nutritional supplement; [FDA] Used as a dietary supplement, flavor additive, and for biochemical research; [HSDB]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
Sources/Uses
An essential amino acid; [Merck Index]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
Nutrition and biochemical research, dietary supplement
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 1241
BIOLOGICAL ACTIVITIES: Possible antiulcer; essential; flavor
USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Threonine. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of August 17, 2010: https://www.ars-grin.gov/duke/

Use (kg; approx.) in Germany (2009): >10000

Consumption (g per capita; approx.) in Germany (2009): 0.122

Calculated removal (%): 92.1

L-Threonine makes up collagen, elastin, and enamel protein. It aids proper fat metabolism in the liver, helps the digestive and intestinal tracts function more smoothly, and assists in metabolism and assimilation.

11.1.1 Use Classification

Food additives -> Flavoring Agents
Flavouring Agent -> FLAVOURING_AGENT; -> JECFA Functional Classes
Flavoring Agents -> JECFA Flavorings Index
Cosmetics -> Hair conditioning; Antistatic
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

11.1.2 Household Products

Household & Commercial/Institutional Products

Information on 29 consumer products that contain Threonine in the following categories is provided:

• Personal Care

11.2 Methods of Manufacturing

Hydrolysis of protein (casein), organic synthesis.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 1241

11.3 U.S. Production

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.
Year
1986
Production Range (pounds)
No Reports
Year
1990
Production Range (pounds)
No Reports
Year
1994
Production Range (pounds)
10 thousand - 500 thousand
Year
1998
Production Range (pounds)
No Reports
Year
2002
Production Range (pounds)
No Reports
US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). L-Threonine (72-19-5). Available from, as of March 23, 2010: https://www.epa.gov/oppt/iur/tools/data/2002-vol.html

11.4 General Manufacturing Information

EPA TSCA Commercial Activity Status
L-Threonine: ACTIVE
EPA TSCA Commercial Activity Status
Threonine: ACTIVE
The amino acids that are incorporated into mammalian protein are alpha-amino acids, with the exception of proline, which is an alpha-imino acid. This means that they have a carboxyl group, an amino nitrogen group, and a side chain attached to a central alpha-carbon. Functional differences among the amino acids lie in the structure of their side chains. In addition to differences in size, these side groups carry different charges at physiological pH (e.g., nonpolar, uncharged but polar, negatively charged, positively charged); some groups are hydrophobic (e.g., branched chain and aromatic amino acids) and some hydrophilic (most others). These side chains have an important bearing on the ways in which the higher orders of protein structure are stabilized and are intimate parts of many other aspects of protein function.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 592, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html

12 Identification

12.1 Analytic Laboratory Methods

Method: AOAC 960.47; Procedure: microbiological, turbidimetric and titrimetric methods; Analyte: threonine; Matrix: vitamin preparations; Detection Limit: not provided.
Official Methods of Analysis of AOAC International, 18th Edition Online. Threonine (72-19-5). Available from, as of March 25, 2010: https://www.aoac.org
Method: AOAC 994.12; Procedure: performic acid oxidation with acid hydrolysis-sodium metabisulfite method; Analyte: threonine; Matrix: feeds; Detection Limit: not provided.
Official Methods of Analysis of AOAC International, 18th Edition Online. Threonine (72-19-5). Available from, as of March 25, 2010: https://www.aoac.org
Method: AOAC 999.13; Procedure: high performance liquid chromatography post-column derivatization; Analyte: threonine; Matrix: feed grade amino acid trade products or in premixes with more than 10% individual amino acid content; Detection Limit: not provided.
Official Methods of Analysis of AOAC International, 18th Edition Online. Threonine (72-19-5). Available from, as of March 25, 2010: https://www.aoac.org

13 Safety and Hazards

13.1 Hazards Identification

13.1.1 GHS Classification

1 of 2
View All
Note
This chemical does not meet GHS hazard criteria for 91.6% (197 of 215) of all reports. Pictograms displayed are for 8.4% (18 of 215) of reports that indicate hazard statements.
GHS Hazard Statements

Not Classified

Reported as not meeting GHS hazard criteria by 197 of 215 companies (only 8.4% companies provided GHS information). For more detailed information, please visit ECHA C&L website.

ECHA C&L Notifications Summary

Aggregated GHS information provided per 215 reports by companies from 2 notifications to the ECHA C&L Inventory.

Reported as not meeting GHS hazard criteria per 197 of 215 reports by companies. For more detailed information, please visit ECHA C&L website.

There is 1 notification provided by 18 of 215 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

13.1.2 Hazard Classes and Categories

Not Classified

13.1.3 Hazards Summary

May cause irritation; [Sigma-Aldrich MSDS]

13.2 Accidental Release Measures

13.2.1 Disposal Methods

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.
SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

13.3 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: L-Threonine
The Australian Inventory of Industrial Chemicals
Chemical: DL-Threonine
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
L-Threonine: Does not have an individual approval but may be used under an appropriate group standard
New Zealand EPA Inventory of Chemical Status
Threonine, (2R,3S)-rel-: Does not have an individual approval but may be used under an appropriate group standard

13.3.1 FDA Requirements

L-Threonine is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.
21 CFR 172.320 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 19, 2010: https://www.ecfr.gov
Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: threonine is included in weight control drug products.
21 CFR 310.545(a) (20) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 22, 2010: https://www.ecfr.gov
Threonine used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.
21 CFR 582.5881 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 3, 2010: https://www.ecfr.gov

13.4 Other Safety Information

Chemical Assessment

IMAP assessments - DL-Threonine: Environment tier I assessment

Evaluation - Chemicals that are unlikely to require further regulation to manage risks to human health

Chemical Assessment

IMAP assessments - L-Threonine: Environment tier I assessment

Evaluation - Chemicals that are unlikely to require further regulation to manage risks to human health

13.4.1 Special Reports

NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C. (2009).[Available from, as of March 10, 2010: http://www.nap.edu/catalog/10490.html]

14 Toxicity

14.1 Toxicological Information

14.1.1 Toxicity Summary

L-Threonine is a precursor to the amino acids glycine and serine. It acts as a lipotropic in controlling fat build-up in the liver. May help combat mental illness and may be very useful in indigestion and intestinal malfunctions. Also, threonine prevents excessive liver fat. Nutrients are more readily absorbed when threonine is present.

14.1.2 Carcinogen Classification

Carcinogen Classification
No indication of carcinogenicity to humans (not listed by IARC).

14.1.3 Acute Effects

14.1.4 Interactions

A methionine-threonine-supplemented low (8.5%) casein diet (8.5CMT) reduced symptoms such as proteinuria in nephritic rats without severe protein malnutrition. ... This study ... examined whether or not L-arginine supplementation to 8.5CMT would exacerbate proteinuria and other symptoms in nephritic rats. Male Wistar rats with glomerulonephritis induced by a single intravenous injection of nephrotoxic serum were fed either a 20% casein diet (control), 8.5% casein diet, 8.5CMT, or L-arginine-supplemented 8.5CMT (8.5CMTA) for 16 days. The 8.5CMTA, as compared with the 8.5CMT, aggravated proteinuria and glomerulonephritis. Administration of L-N(G)-nitroarginine methyl ester, an inhibitor of nitric oxide synthase, to 8.5CMTA-fed nephritic rats by drinking water for 14 days canceled the adverse effect of L-arginine on proteinuria and histopathological damage in glomeruli. These results suggest that the supplementation of L-arginine makes exacerbation via nitric oxide production in glomerulonephritis.
Nihei T et al; Biosci, Biotech, Biochem 65 (5): 1155-62 (2001). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11440131
Rats fed a low-protein diet and administered 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC) orally at 30 umol/kg/day (10 mg/kg/day) or fed a low-protein diet containing 5 ppm NTBC develop lesions to the cornea of the eye within 3-8 days of exposure with an incidence of about 80%. This treatment also produces a marked inhibition of both hepatic and renal 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, an induction of hepatic but not renal tyrosine amino transferase activity, and a marked tyrosinemia in the plasma and aqueous humor. The extent of tyrosinemia and changes in the activity of tyrosine catabolic enzymes are similar to those reported for rats fed a normal protein diet and administered NTBC orally at 30 mumol/kg/day. However, the onset of corneal lesions occurs much earlier in rats fed a low-protein diet. The adverse ocular effects of NTBC can be alleviated by supplementing the low-protein diet with 1% w/w threonine. The protection afforded by threonine inclusion in the diet was not due to any amelioration in the extent of inhibition of hepatic HPPD activity or reduction in the extent of the tyrosinemia as measured 8 days after treatment. Rats fed L-tyrosine at 5% w/w in a low-protein diet rapidly develop lesions to the cornea of the eye, which are associated with a marked tyrosinemia, increased hepatic tyrosine aminotransferase activity, and about a 50% reduction in the activity of hepatic HPPD. The onset of corneal lesions produced by feeding a high tyrosine diet could be delayed, but not prevented, by inclusion of 1% w/w threonine in the low-protein diet. The basis for the beneficial effect of dietary supplementation of threonine in alleviating the corneal lesions produced by NTBC is unclear. However, our findings do illustrate that protein deficiency limits the ability of the rat to respond to a tyrosine load produced by inhibition of HPPD.
Lock EA et al; Toxicol Appl Pharmacol 150 (1): 125-32 (1998). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9630461

14.1.5 Antidote and Emergency Treatment

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

14.1.6 Human Toxicity Excerpts

/OTHER TOXICITY INFORMATION/ Threonine also has been studied in low birth weight infants. In a study of 163 low birth weight infants, threonine serum concentrations were directly related to the threonine concentrations of the formula. The authors suggested that threonine intakes should not exceed about 140 mg/kg body weight/day for premature infants.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 731, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/OTHER TOXICITY INFORMATION/ There is no evidence that amino acids derived from usual or even high intakes of protein from foodstuffs present any risk.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 695, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/OTHER TOXICITY INFORMATION/ Serum threonine concentration was determined during the first month of life in 163 low birthweight infants fed on either human milk, various adapted formulae, or total parenteral nutrition. On the pooled data, a significant positive relationship was found between the serum threonine concentration and threonine intake. However, the increase of the serum threonine level is more marked in the infants with the lowest actual gestational age; with a high threonine intake, the most premature infants have serum threonine levels twice as high (58.1 vs 31.7 uM/dL) as term infants. Therefore, threonine metabolism seems to be impeded in preterm infants. Considering the cord blood concentration of threonine (26.8 +/- 5.1 uM/dL) and the possible hazardous effect of hyperthreoninemia, it is suggested that threonine intake should not exceed 1200 uM (143 mg)/kg bodyweight/day in premature infants and that the amino acid composition of the diet should probably be modified in order to satisfy their protein requirement.
Rigo J, Senterre J; JPEN J Parenter Enteral Nutr 4 (1): 15-7 (1980).
/OTHER TOXICITY INFORMATION/ The threonine content of most of the infant formulas currently on the market is approximately 20% higher than the threonine concentration in human milk. Due to this high threonine content the plasma threonine concentrations are up to twice as high in premature infants fed these formulas than in infants fed human milk. Increasing the threonine in plasma leads to increasing brain glycine and thereby affects the neurotransmitter balance in the brain. This may have consequences for brain development during early postnatal life. Therefore, excessive threonine intake during infant feeding should be avoided.
Boehm G et al; Pediatr Res 44 (6): 900-6 (1998).

14.1.7 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ The purpose of this study was to determine whether an addition of dietary limiting amino acids affected urea synthesis in rats fed a low gluten diet. Experiments were done on three groups of rats given diets containing 10% gluten, 10% gluten +0.5% L-lysine or 10% gluten+0.5% L-lysine, 0.2% L-threonine and 0.2% L-methionine for 10 d. The urinary excretion of urea, and the liver concentrations of serine and ornithine decreased with the addition of dietary L-lysine, L-threonine and L-methionine. The fractional and absolute rates of protein synthesis in tissues increased with the treatment of limiting amino acids. The activities of hepatic urea-cycle enzymes was not related to the urea excretion. These results suggest that the addition of limiting amino acids for the low gluten diet controls the protein synthesis in tissues and hepatic ornithine and decline in urea synthesis.
Tujioka K et al; Amino Acids 28 (3): 297-303 (2005). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15789139
/LABORATORY ANIMALS: Acute Exposure/ Rats quickly recognize and reject diets deficient in an essential amino acid. The purpose of this study was to determine whether the anterior piriform cortex (APC), the site traditionally recognized as the amino acid chemosensor, plays a role in this early behavior. Rats had cannulae implanted bilaterally into the APC, and were injected with either saline vehicle or 2 nmoles of threonine (n = 6 per group). All rats were then fed a diet imbalanced with respect to threonine. The threonine-injected group had first meals of longer duration and consumed more food. These data conformed to expectations derived from earlier studies of responses to the first meal of an amino acid imbalanced diet. /It was concluded/ that the concentration of the dietary limiting amino acid in the APC regulates acceptance and rejection of amino acid deficient diets.
Russell MC et al; Nutr Neurosci 6 (4): 247-51 (2003). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12887141
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In weanling pigs, adding 0.5, 1, 2, or 4% L-threonine to a 20% crude protein diet did not change weight gain, food intake, and gain:feed ratios in comparison to the controls.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 731, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The results of neurochemical and behavioral studies in the developing rat suggest that despite numerous possible effects of threonine on brain constituents, moderate hyperthreoninemia does not impair markedly the development of the central nervous system.
Castagne V et al; Pharmacol, Biochem, Behav 55 (4): 653-62 (1996). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8981597
/OTHER TOXICITY INFORMATION/ In rats fed 5% threonine added to a 10% casein diet, weight gain was reduced compared to controls fed casein alone but there were no changes in liver weight or hepatic DNA, RNA, or protein content.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 730, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html

14.1.8 Non-Human Toxicity Values

LD50 rat ip 3098 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3460

14.2 Ecological Information

14.2.1 Natural Pollution Sources

(L)-Threoniine is one of the nine indispensable amino acids that cannot be synthesized to meet body needs in animals and therefore must be provided in the diet(1). It has been identified in oat protein(2).
(1) NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C. (2005). Available from, as of August 17, 2010: https://books.nap.edu/openbook.php?record_id=10490&page=589
(2) O'Neil MJ, ed; The Merck Index. 14th ed., Whitehouse Station, NJ: Merck and Co., Inc., p. 1611 (2006)

14.2.2 Plant Concentrations

Plants with the highest amount of Threonine(1).
Genus species
Nasturtium officinale R. BR.
Commons name(s)
Berro, Watercress
Concentration
1,330 - 26,600 ppm
Area of Plant
Herb
Genus species
Cucurbita foetidissima HBK.
Commons name(s)
Buffalo Gourd
Concentration
4,605 - 26,000 ppm
Area of Plant
Seed
Genus species
Moringa oleifera LAM.
Commons name(s)
Ben Nut, Benzolive Tree, Drumstick Tree, Horseradish Tree, Jacinto (Sp.), Moringa, West Indian Ben
Concentration
4,110 - 19,260 ppm
Area of Plant
Shoot
Genus species
Phaseolus vulgaris subsp. var. vulgaris
Commons name(s)
Black Bean, Dwarf Bean, Field Bean, Flageolet Bean, French Bean, Garden Bean, Green Bean, Haricot, Haricot Bean, Haricot Vert, Kidney Bean, Navy Bean, Pop Bean, Popping Bean, Snap Bean, String Bean, Wax Bean
Concentration
1,760 - 18,925 ppm
Area of Plant
Sprout Seedling
Genus species
Ipomoea aquatica FORSSKAL
Commons name(s)
Swamp Cabbage, Water Spinach
Concentration
1,400 - 18,590 ppm
Area of Plant
Leaf
Genus species
Glycine max (L.) MERR.
Commons name(s)
Soybean
Concentration
15,850 - 17,330 ppm
Area of Plant
Seed
Genus species
Ceratonia siliqua L.
Commons name(s)
Carob, Locust Bean, St.John's-Bread
Concentration
16,920 ppm
Area of Plant
Seed
Genus species
Avena sativa L.
Commons name(s)
Oats
Concentration
16,000 ppm
Area of Plant
Plant
Genus species
Rehmannia glutinosa (GAERTN.) LIBOSCH.
Commons name(s)
Chinese Foxglove
Concentration
1,000 - 16,000 ppm
Area of Plant
Root
Genus species
Citrullus lanatus (THUNB.) MATSUM. &amp; NAKAI
Commons name(s)
Watermelon
Concentration
15,300 ppm
Area of Plant
Seed
Genus species
Lupinus albus L.
Commons name(s)
White Lupine
Concentration
13,310 - 14,860 ppm
Area of Plant
Seed
Genus species
Aloe vera (L.) BURM. f.
Commons name(s)
Aloe, Bitter Aloes
Concentration
14,652 ppm
Area of Plant
Leaf
Genus species
Spinacia oleracea L.
Commons name(s)
Spinach
Concentration
1,220 - 14,489 ppm
Area of Plant
Plant
Genus species
Allium schoenoprasum L.
Commons name(s)
Chives
Concentration
1,110 - 13,875 ppm
Area of Plant
Leaf
Genus species
Corchorus olitorius L.
Commons name(s)
Jew's Mallow, Mulukiya, Nalta Jute
Concentration
890 - 13,350 ppm
Area of Plant
Leaf
Genus species
Mucuna pruriens (L.) DC.
Commons name(s)
Cowage, Velvetbean
Concentration
6,250 - 13,250 ppm
Area of Plant
Seed
Genus species
Psophocarpus tetragonolobus (L.) DC.
Commons name(s)
Asparagus Pea, Goa Bean, Winged Bean
Concentration
11,790 - 12,863 ppm
Area of Plant
Seed
Genus species
Sesamum indicum L.
Commons name(s)
Ajonjoli (Sp.), Beni, Benneseed, Sesame, Sesamo (Sp.)
Concentration
7,360 - 12,396 ppm
Area of Plant
Seed
Genus species
Amaranthus sp.
Commons name(s)
Pigweed
Concentration
990 - 11,910 ppm
Area of Plant
Leaf
Genus species
Lablab purpureus (L.) SWEET
Commons name(s)
Bonavist Bean, Hyacinth Bean, Lablab Bean
Concentration
1,430 - 11,789 ppm
Area of Plant
Seed
Genus species
Sinapis alba L.
Commons name(s)
White Mustard
Concentration
10,950 - 11,720 ppm
Area of Plant
Seed
Genus species
Colocasia esculenta (L.) SCHOTT
Commons name(s)
Taro
Concentration
1,670 - 11,645 ppm
Area of Plant
Leaf
Genus species
Lens culinaris MEDIK.
Commons name(s)
Lentil
Concentration
10,060 - 11,325 ppm
Area of Plant
Seed
Genus species
Asparagus officinalis L.
Commons name(s)
Asparagus
Concentration
850 - 10,968 ppm
Area of Plant
Shoot
Genus species
Vicia faba L.
Commons name(s)
Broadbean, Faba Bean, Habas
Concentration
2,080 - 10,950 ppm
Area of Plant
Seed
Genus species
Lens culinaris MEDIK.
Commons name(s)
Lentil
Concentration
3,280 - 10,935 ppm
Area of Plant
Sprout Seedling
Genus species
Acacia farnesiana (L.) WILLD.
Commons name(s)
Cassie, Huisache, Opopanax, Popinac, Sweet Acacia
Concentration
2,000 - 10,730 ppm
Area of Plant
Leaf
Genus species
Psophocarpus tetragonolobus (L.) DC.
Commons name(s)
Asparagus Pea, Goa Bean, Winged Bean
Concentration
4,510 - 10,587 ppm
Area of Plant
Tuber
Genus species
Brassica chinensis L.
Commons name(s)
Bok-Choy, Celery Cabbage, Celery Mustard, Chinese Cabbage, Chinese Mustard, Chinese White Cabbage, Pak-Choi
Concentration
490 - 10,471 ppm
Area of Plant
Leaf
Genus species
Valerianella locusta (L.) LATERRADE
Commons name(s)
Corn Salad, Lamb's Lettuce
Concentration
750 - 10,415 ppm
Area of Plant
Plant
(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Threonine. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of August 17, 2010: https://www.ars-grin.gov/duke/

14.2.3 Milk Concentrations

The threonine content of most of the infant formulas currently on the market is approximately 20% higher than the threonine concentration in human milk. Due to this high threonine content the plasma threonine concentrations are up to twice as high in premature infants fed these formulas than in infants fed human milk. To study the effect of different threonine intakes on plasma and tissue amino acid concentrations, 24 young male Wistar rats were fed three experimental diets based on a mixture of bovine proteins with a whey protein/casein ratio of 60/40 with different threonine contents [group A, 0.86 g of threonine/100 g (n = 8); group B, 1.03 g of threonine/100 g (n = 8); group C, 2.21 g of threonine/100 g (n = 8)]. Eight animals were fed a typical rat diet based on bovine casein as controls. After a feeding period of 15 d, amino acids were measured in plasma and in homogenates of the cerebral cortex, brain stem, liver, and muscle. There was a significant correlation between threonine intake and plasma threonine levels (r = 0.687, p < 0.001). The plasma threonine concentration correlated significantly with the threonine concentration in the cortex (r = 0.821, p < 0.01) and the brain stem (r = 0.882, p < 0.01). There was a positive significant correlation between threonine and glycine concentrations in the cortex (r = 0.673, p < 0.01), and the brain stem (r = 0.575, p < 0.01), whereas the glycine concentration decreased with increasing threonine intakes in the liver and muscle. The presented data indicate that increasing the threonine in plasma leads to increasing brain glycine and thereby affects the neurotransmitter balance in the brain. This may have consequences for brain development during early postnatal life. Therefore, excessive threonine intake during infant feeding should be avoided.
Boehm G et al; Pediatr Res 44(6): 900-6 (1998).

14.2.4 Probable Routes of Human Exposure

NIOSH (NOES Survey 1981-1983) has statistically estimated that 18,524 workers (13,980 of these were female) were potentially exposed to threonine in the US(1).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from, as of Feb 22, 2010: https://www.cdc.gov/noes/

15 Associated Disorders and Diseases

Disease
Heart failure
References
Disease
Early preeclampsia
References
PubMed: 22494326
Disease
Pregnancy
References

PubMed: 3252730, 663967, 12833386, 2994907, 17704099, 12698507, 17061063, 16925883, 22420377, 18059417, 22494326, 23159745, 23313728, 23535240, 24704061

The Merck Manual, 17th ed. Mark H. Beers, MD, Robert Berkow, MD, eds. Whitehouse Station, NJ: Merck Research Labs, 1999.

Disease
Late-onset preeclampsia
References
PubMed: 23159745
Disease
Fumarase deficiency
References

PubMed: 26078636, 20549362, 24182348, 6616883, 16972175

MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Disease
Obesity
References

PubMed: 15899597, 16253646, 2401584, 17264178, 1783639, 26505825, 17408529, 18997681, 24740590, 23108202, 26910390

Metabolomics reveals determinants of weight loss during lifestyle intervention in obese children

Disease
Citrullinemia type II, neonatal-onset
References
PubMed: 11281457
Disease
Pyridoxamine 5-prime-phosphate oxidase deficiency
References
Disease
Leukemia
References
Disease
Irritable bowel syndrome
References
Disease
Colorectal cancer
References

PubMed: 7482520, 19006102, 23940645, 24424155, 20156336, 19678709, 22148915, 25105552, 21773981, 25037050, 27015276, 27107423, 27275383, 28587349

Silke Matysik, Caroline Ivanne Le Roy, Gerhard Liebisch, Sandrine Paule Claus. Metabolomics of fecal samples: A practical consideration. Trends in Food Science & Technology. Vol. 57, Part B, Nov. 2016, p.244-255: http://www.sciencedirect.com/science/article/pii/S0924224416301984

Disease
Rheumatoid arthritis
References

PubMed: 6589104, 16277678, 15338487, 10361015, 15249323

Tie-juan ShaoZhi-xing HeZhi-jun XieHai-chang LiMei-jiao WangCheng-ping Wen. Characterization of ankylosing spondylitis and rheumatoid arthritis using 1H NMR-based metabolomics of human fecal extracts. Metabolomics. April 2016, 12:70: https://link.springer.com/article/10.1007/s11306-016-1000-2

Disease
Perillyl alcohol administration for cancer treatment
References
Disease
Pancreatic cancer
References
Disease
Periodontal disease
References
PubMed: 20300169
Disease
Frontotemporal dementia
References
PubMed: 23857558
Disease
Lewy body disease
References
PubMed: 23857558
Disease
Attachment loss
References
PubMed: 31026179
Disease
Missing teeth
References
PubMed: 31026179
Disease
Periodontal Probing Depth
References
PubMed: 31026179
Disease
Autosomal dominant polycystic kidney disease
References
Disease
Eosinophilic esophagitis
References
Mordechai, Hien, and David S. Wishart

16 Literature

16.1 Consolidated References

16.2 NLM Curated PubMed Citations

16.3 Springer Nature References

16.4 Thieme References

16.5 Wiley References

16.6 Nature Journal References

16.7 Chemical Co-Occurrences in Literature

16.8 Chemical-Gene Co-Occurrences in Literature

16.9 Chemical-Disease Co-Occurrences in Literature

17 Patents

17.1 Depositor-Supplied Patent Identifiers

17.2 WIPO PATENTSCOPE

17.3 Chemical Co-Occurrences in Patents

17.4 Chemical-Disease Co-Occurrences in Patents

17.5 Chemical-Gene Co-Occurrences in Patents

18 Interactions and Pathways

18.1 Protein Bound 3D Structures

18.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Conformer

18.2 Chemical-Target Interactions

18.3 Pathways

19 Biological Test Results

19.1 BioAssay Results

20 Taxonomy

WormJam Metabolites Local CSV for MetFrag | DOI:10.5281/zenodo.3403364
WormJam: A consensus C. elegans Metabolic Reconstruction and Metabolomics Community and Workshop Series, Worm, 6:2, e1373939, DOI:10.1080/21624054.2017.1373939
Zebrafish Pathway Metabolite MetFrag Local CSV (Beta) | DOI:10.5281/zenodo.3457553
The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

21 Classification

21.1 MeSH Tree

21.2 NCI Thesaurus Tree

21.3 ChEBI Ontology

21.4 KEGG: Metabolite

21.5 KEGG: JP15

21.6 KEGG: Risk Category of Japanese OTC Drugs

21.7 ChemIDplus

21.8 ChEMBL Target Tree

21.9 UN GHS Classification

21.10 EPA CPDat Classification

21.11 NORMAN Suspect List Exchange Classification

21.12 CCSBase Classification

21.13 EPA DSSTox Classification

21.14 Consumer Product Information Database Classification

21.15 EPA TSCA and CDR Classification

21.16 LOTUS Tree

21.17 EPA Substance Registry Services Tree

21.18 MolGenie Organic Chemistry Ontology

22 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
  2. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  3. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  5. DTP/NCI
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  6. EPA Chemicals under the TSCA
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  7. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  8. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  9. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. Hazardous Substances Data Bank (HSDB)
  11. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  12. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  13. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  14. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Threonine(l)
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  15. ChEBI
  16. E. coli Metabolome Database (ECMDB)
    LICENSE
    ECMDB is offered to the public as a freely available resource.
    https://ecmdb.ca/citations
  17. LOTUS - the natural products occurrence database
    LICENSE
    The code for LOTUS is released under the GNU General Public License v3.0.
    https://lotus.nprod.net/
  18. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  19. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  20. Toxin and Toxin Target Database (T3DB)
    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  21. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  22. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  23. Consumer Product Information Database (CPID)
    LICENSE
    Copyright (c) 2024 DeLima Associates. All rights reserved. Unless otherwise indicated, all materials from CPID are copyrighted by DeLima Associates. No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://www.whatsinproducts.com/contents/view/1/6
    Consumer Products Category Classification
    https://www.whatsinproducts.com/
  24. Cosmetic Ingredient Review (CIR)
  25. EPA Chemical and Products Database (CPDat)
  26. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
    LICENSE
    Copyright (c) 2022 Haz-Map(R). All rights reserved. Unless otherwise indicated, all materials from Haz-Map are copyrighted by Haz-Map(R). No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://haz-map.com/About
  27. DailyMed
  28. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) licence.
    https://www.who.int/about/policies/publishing/copyright
  29. IUPAC Digitized pKa Dataset
  30. ECI Group, LCSB, University of Luxembourg
    LICENSE
    Data: CC-BY 4.0; Code: Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    L-threonine
  31. Natural Product Activity and Species Source (NPASS)
  32. EU Food Improvement Agents
  33. FDA Substances Added to Food
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  34. Flavor and Extract Manufacturers Association (FEMA)
  35. SpectraBase
  36. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  37. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  38. Japan Chemical Substance Dictionary (Nikkaji)
  39. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Drugs listed in the Japanese Pharmacopoeia
    http://www.genome.jp/kegg-bin/get_htext?br08311.keg
    Risk category of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08312.keg
  40. Kruve Lab, Ionization & Mass Spectrometry, Stockholm University
    threonine
  41. MarkerDB
    LICENSE
    This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
    https://markerdb.ca/
  42. Metabolomics Workbench
  43. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  44. Nature Chemistry
  45. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  46. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  47. Protein Data Bank in Europe (PDBe)
  48. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  49. Springer Nature
  50. The Cambridge Structural Database
  51. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  52. Wikidata
  53. Wikipedia
  54. Wiley
  55. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  56. PubChem
  57. GHS Classification (UNECE)
  58. EPA Substance Registry Services
  59. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  60. PATENTSCOPE (WIPO)
  61. NCBI
CONTENTS