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Methionine

PubChem CID
6137
Structure
Methionine_small.png
Methionine_3D_Structure.png
Methionine__Crystal_Structure.png
Molecular Formula
Synonyms
  • L-methionine
  • 63-68-3
  • methionine
  • h-Met-oh
  • (S)-2-Amino-4-(methylthio)butanoic acid
Molecular Weight
149.21 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
Minute hexagonal plates from dilute alcohol. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
L-methionine is the L-enantiomer of methionine. It has a role as a nutraceutical, a micronutrient, an antidote to paracetamol poisoning, a human metabolite and a mouse metabolite. It is an aspartate family amino acid, a proteinogenic amino acid, a methionine and a L-alpha-amino acid. It is a conjugate base of a L-methioninium. It is a conjugate acid of a L-methioninate. It is an enantiomer of a D-methionine. It is a tautomer of a L-methionine zwitterion.
A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals.
See also: Zinc methionine sulfate (is active moiety of) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Methionine.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-Met-OH
Sequence
M
PLN
H-M-OH
HELM
PEPTIDE1{M}$$$$
IUPAC
L-methionine

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

(2S)-2-amino-4-methylsulfanylbutanoic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

3.1.2 InChI

InChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.3 InChIKey

FFEARJCKVFRZRR-BYPYZUCNSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.4 SMILES

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

3.2 Molecular Formula

C5H11NO2S
Computed by PubChem 2.2 (PubChem release 2021.10.14)

3.3 Other Identifiers

3.3.1 CAS

63-68-3
3654-96-4
58576-49-1
59-51-8

3.3.3 Deprecated CAS

1437749-32-0, 1437749-60-4, 1437749-65-9, 1437749-75-1, 1437749-80-8, 1437769-00-0, 1437870-94-4, 1437870-95-5, 1437870-97-7, 1437870-98-8, 1437871-20-9, 1463481-01-7, 1463481-06-2, 1463481-15-3, 1463481-19-7, 1463481-23-3, 1463481-27-7, 1463481-31-3, 1463481-37-9, 1463481-41-5, 1463481-46-0, 1463481-51-7, 1463481-58-4, 1463481-73-3, 1463481-80-2, 1463481-89-1, 1463610-75-4, 1463610-76-5, 1466415-57-5, 24425-78-3, 7005-18-7
1105707-18-3, 192948-75-7
1437749-32-0, 1437749-60-4, 1437749-65-9, 1437749-75-1, 1437749-80-8, 1437769-00-0, 1437870-94-4, 1437870-95-5, 1437870-97-7, 1437870-98-8, 1437871-20-9, 1463481-06-2, 1463481-15-3, 1463481-19-7, 1463481-23-3, 1463481-27-7, 1463481-31-3, 1463481-37-9, 1463481-41-5, 1463481-46-0, 1463481-51-7, 1463481-58-4, 1463481-73-3, 1463481-80-2, 1463481-89-1, 1463610-75-4, 1463610-76-5, 1466415-57-5, 24425-78-3, 7005-18-7

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 HMDB ID

3.3.11 KEGG ID

3.3.12 Metabolomics Workbench ID

3.3.13 NCI Thesaurus Code

3.3.14 Nikkaji Number

3.3.15 NSC Number

3.3.16 PharmGKB ID

3.3.17 RXCUI

3.3.18 Wikidata

3.3.19 Wikipedia

3.4 Synonyms

3.4.1 MeSH Entry Terms

  • L-Isomer Methionine
  • L-Methionine
  • Liquimeth
  • Methionine
  • Methionine, L Isomer
  • Methionine, L-Isomer
  • Pedameth

3.4.2 Depositor-Supplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name
Molecular Weight
Property Value
149.21 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-1.9
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
2
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
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
149.05104977 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
149.05104977 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
88.6 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
9
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
97
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
1
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

Minute hexagonal plates from dilute alcohol. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Solid; [Merck Index] Colorless or white solid with a faint odor; [HSDB] White powder; [Sigma-Aldrich MSDS]
Solid

4.2.2 Color / Form

Minute hexagonal plates from dilute alcohol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1032
Colorless or white, lustrous plates or as white, crystalline powder
FCC; Food Chemicals Codex. Committee on Food Chemicals Codex, Food and Nutrition Board, Institute of Medicine. 5th. Washington, DC: National Academy Press p. 286 (2003)

4.2.3 Odor

Faint
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 752

4.2.4 Taste

Sulfurous
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA2: 79 (1985)

4.2.5 Boiling Point

sublimes at 367 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
181 °C (decomposes)
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-328

4.2.6 Melting Point

536 to 540 °F decomposes 541.4-543.2 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
283 dec °C
PhysProp
280-282 °C (decomposes, sealed capillary)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1032
284 °C

4.2.7 Solubility

Soluble (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
56600 mg/L (at 25 °C)
YALKOWSKY,SH & DANNENFELSER,RM (1992)
Soluble in water but the crystals are somewhat water-repellant at first
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1032
Soluble in warm dilute alcohol; insoluble in absolute alcohol, ether, petroleum ether, benzene, acetone
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1032
Slightly soluble in acetic acid
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-328
In water, 56.6 g/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. 175
56.6 mg/mL
YALKOWSKY,SH & DANNENFELSER,RM (1992)

4.2.8 Density

1.178 at 68 °F (NTP, 1992) - Denser than water; will sink
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

4.2.9 Vapor Pressure

0.00000052 [mmHg]

4.2.10 LogP

-1.87
HANSCH,C ET AL. (1995)
log Kow = -1.87
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 15
-1.87
HANSCH,C ET AL. (1995)

4.2.11 LogS

-0.42
ADME Research, USCD

4.2.12 Optical Rotation

Specific optical rotation: +8.12 deg at 25 °C/D (c = 0.8); -21.19 deg at 25 °C/D (c = 0.8 in 0.2N HCl) /Methione, D-form/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1032
Specific optical rotation: 22.5 deg at 25 °C/D (1 N HCl)
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. V4: 3432
Specific optical rotation: -8.2 deg at 25 °C/D (c = 0.8); +23.40 at 20 °C/D (c = 5.0 in 3.0N HCl)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1032

4.2.13 Decomposition

When heated to decomposition it emits very toxic fumes of /nitric oxide/ and /sulfur oxide/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2334

4.2.14 pH

pH (1% aqueous solution) = 5.6-6.1
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 752

4.2.15 Ionization Efficiency

1 of 2
Ionization mode
Positive
logIE
2.7
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
-0.62
pH
10.5
Instrument
Agilent XCT
Ion source
Electrospray ionization
Additive
ammonia (10nM)
Organic modifier
MeCN (80%)

4.2.16 Dissociation Constants

pKa
2.28 (at 25 °C)
ULLMANN VA2:63 (1985)
pKa = 2.28; pK2 = 9.21
Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). NY, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.

4.2.17 Collision Cross Section

127 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine]

133.65 Ų [M+H]+ [CCS Type: DT; Method: stepped-field]

152.05 Ų [M-H]- [CCS Type: DT; Method: stepped-field]

134.08 Ų [M+H]+ [CCS Type: DT; Method: stepped-field]

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

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

132.9 Ų [M+H]+

133.6 Ų [M+H]+

140.5 Ų [M-H]-

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

4.2.18 Other Experimental Properties

Platelets from alcohol. mp 281 °C (decomposes), density 1.340; pKa1 = 2.28, pKa2 = 9.21; pH of 1% aqueous solution 5.6-6.1; Rf value 0.77. Solubility in water (g/L) at 0 °C: 18.18; at 25 °C: 33.81; at 50 °C: 60/.70; at 75 °C: 15.2 °C. Soluble in dilute acids, alkalies. Very slightly soluble in 95% alcohol. Insoluble in ether. /Methionine, DL-form/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1032
UV: 1-65 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /Methionine (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. V4: 3431

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
4.3.1.1 Animal Drugs
Pharmaceuticals -> UK Veterinary Medicines Directorate List
S104 | UKVETMED | UK Veterinary Medicines Directorate's List | DOI:10.5281/zenodo.7802119

4.3.2 Cosmetics

Cosmetic ingredients (Methionine) -> CIR (Cosmetic Ingredient Review)
Antistatic; Hair conditioning; Skin conditioning
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

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
2.09:3.48, 2.12:9.80, 2.17:2.90, 2.19:3.78, 2.15:3.07, 3.85:8.22, 2.18:5.50, 2.21:1.68, 3.85:8.15, 2.10:5.92, 2.20:3.73, 2.17:5.22, 3.84:6.93, 2.62:15.07, 2.07:1.26, 2.12:100.00, 2.15:2.58, 2.23:1.38, 3.86:6.80, 2.21:2.29, 2.63:25.65, 2.65:13.19
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Spectra ID
Instrument Type
Bruker
Solvent
D2O
pH
7.4
Shifts [ppm]:Intensity
2.17:0.54, 2.21:0.47, 3.85:1.10, 2.13:1.43, 2.19:0.71, 2.64:2.41, 2.09:0.69, 2.17:0.98, 2.16:0.44, 3.85:1.12, 2.18:1.06, 2.21:0.30, 2.11:1.19, 3.84:0.96, 2.14:0.49, 2.19:0.72, 2.63:4.75, 3.86:0.93, 2.12:15.00, 2.62:2.76
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5.1.2 13C NMR Spectra

1 of 5
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13C NMR Spectra
13C NMR: 135 (Johnson and Jankowski, Carbon-13 NMR Spectra, John Wiley & Sons, New York) /Methionine (DL)/
2 of 5
View All
Spectra ID
Instrument Type
Bruker
Frequency
125 MHz
Solvent
Water
pH
7.00
Shifts [ppm]:Intensity
-0.00:5.63, 31.54:55.50, 32.53:54.72, 16.64:36.56, 176.96:19.01, 56.81:46.00
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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)
3.86:2.65, 2.14:3.85, 2.16:2.63, 2.18:2.10, 2.64:2.08, 2.64:2.65, 3.58:2.12, 2.16:2.17, 2.13:2.12, 2.17:2.62, 3.86:2.63, 2.17:2.08, 2.63:2.62, 2.63:2.20, 2.64:2.14, 2.63:2.22, 2.13:2.10, 3.86:2.62, 2.17:2.19, 2.64:2.63, 3.86:2.19, 2.63:2.16, 3.86:3.86, 3.86:3.84, 3.86:2.14, 2.64:2.12, 2.64:3.85, 2.17:2.65, 2.64:2.10, 2.18:2.20, 2.63:2.19, 3.86:2.17, 2.13:2.08, 2.30:2.30
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5.2.2 1H-13C NMR Spectra

2D NMR Spectra Type
1H-13C HSQC
Spectra ID
Instrument Type
Bruker
Frequency
600 MHz
Solvent
Water
pH
7.00
Shifts [ppm] (F2:F1):Intensity
2.63:31.58:1.00, 3.85:56.84:0.60, 2.10:16.57:0.10, 2.18:32.72:0.35
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5.3 Mass Spectrometry

5.3.1 GC-MS

1 of 13
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Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

104.0 1

131.0 0.22

130.0 0.18

221.0 0.12

116.0 0.11

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Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

176.0 1

128.0 0.88

177.0 0.15

100.0 0.12

129.0 0.12

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5.3.2 MS-MS

1 of 8
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Spectra ID
Ionization Mode
Positive
Top 5 Peaks

61.01049 100

56.04918 97

74.02289 13.30

44.97952 9.20

102.05554 5.50

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Spectra ID
Ionization Mode
Negative
Top 5 Peaks

46.99551 100

57.72199 2.40

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5.3.3 LC-MS

1 of 31
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Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6530 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Retention Time
0.216 min
Precursor m/z
150.0583
Precursor Adduct
[M+H]+
Top 5 Peaks

61.0103 999

56.0491 917

87.0256 70

104.0508 62

84.044 34

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License
CC BY
2 of 31
View All
Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6530 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Retention Time
0.216 min
Precursor m/z
150.0583
Precursor Adduct
[M+H]+
Top 5 Peaks

56.0495 999

61.0103 625

104.0522 548

133.0301 426

150.0569 150

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License
CC BY

5.3.4 Other MS

1 of 6
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Other MS
MASS: 442 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63) /Methionine (DL)/
Other MS
MASS: 54346 (NIST/EPA/MSDC Mass Spectral Database, 1990 version)
2 of 6
View All
Authors
Miyagawa H, Akimoto S, Yamasaki K, GL Sciences Inc.
Instrument
GCMS-2010 Plus, Shimadzu
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Column Name
InertCap 5MS/NP 0.25 mmI.D. x 30 m, df=0.25 um
Retention Time
596.79
Top 5 Peaks

176.1 999

128.1 647

147.1 152

177.1 135

219.1 117

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License
CC BY-SA

5.4 UV Spectra

MAX ABSORPTION (0.01 N HCL): 208 NM (SHOULDER) (LOG E= 3.2)
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-378

5.5 IR Spectra

IR Spectra
IR: 2549 (Coblentz Society Spectral Collection) /Methionine (DL)/

5.5.1 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.
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2 of 2
Technique
KBr WAFER
Source of Sample
Tokyo Kasei Kogyo Company, Ltd., Tokyo, Japan
Catalog Number
M 102
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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5.5.2 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
Sigma-Aldrich Inc.
Catalog Number
M9375
Lot Number
78K1189
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Sample
Aldrich
Catalog Number
151696
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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5.6 Raman Spectra

1 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Sigma-Aldrich Company LLC
Catalog Number
<a href=https://www.sigmaaldrich.com/US/en/product/sial/M9625>M9625</a>
Lot Number
108K01611
Copyright
Copyright © 2015-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Catalog Number
151696
Copyright
Copyright © 2017-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2017-2024 John Wiley & Sons, Inc. All Rights Reserved.
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7 Chemical Vendors

8 Drug and Medication Information

8.1 Drug Indication

Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.

8.2 FDA National Drug Code Directory

8.3 Drug Labels

Active ingredient and drug
Homeopathic product and label

8.4 Clinical Trials

8.4.1 ClinicalTrials.gov

8.4.2 EU Clinical Trials Register

8.4.3 NIPH Clinical Trials Search of Japan

8.5 Therapeutic Uses

A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
Methionine ... enhances the synthesis of glutathione and is used as an alternative to acetylcysteine in the treatment of paracetamol poisoning.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.1450.
... Many of signs of toxicity /of selenium poisoning/ can be prevented by high-protein diets, and by methionine in the presence of Vitamin E.
Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 456
In Europe, oral methionine (10 g over 12 hours) is approved as an agent to restore depleted glutathione stores and prevent hepatotoxicity after large acetaminophen ingestions. N-Acetyl-L-cysteine remains the preferred antidote for acetaminophen overdose in the United States, Canada, Scotland, and most of England.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 80
For more Therapeutic Uses (Complete) data for (L)-Methionine (9 total), please visit the HSDB record page.

8.6 Drug Warnings

Methionine may cause nausea, vomiting, drowsiness, and irritability. It should not be used in patients with acidosis. Methionine may aggravate hepatic encephalopathy in patients with established liver damage; it should be used with caution in patients with severe liver disease.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p. 1450.
Vomiting is a common adverse effect.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 163
Methionine ... may exacerbate hepatic encephalopathy when administered more than 10 hours postingestion.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 163
The death of a control subject after an oral load of methionine for a study of the possible relationship between homocysteine and Alzheimer's disease is reported. The subject developed postload plasma concentrations of methionine far beyond those reported previously in humans given the usual oral loading dose of methionine (100 mg/kg body wt). Her preload plasma metabolite values rule out known genetic diseases that might predispose one to unusually high methionine concentrations. The most likely explanation for these events is that the subject received a substantial overdose of methionine. The possibility that extremely high methionine concentrations may lead to severe cerebral effects is discussed, and it is recommended that any move to increase the sensitivity of the usual methionine loading test by increasing the dose of methionine either not be undertaken or be taken only with extreme care.
Cottington EM et al; Arterioscler Thromb Vasc Biol 22 (6): 1046-50 (2002).
When studying genetic factors in arteriosclerosis /the authors/ recorded acute complications during a standard methionine loading test (with a dose of 100 mg/kg bw) and assessed a 30-day mortality in a group of 296 patients with coronary artery or peripheral arterial disease and in 591 controls. Acute complications were observed in 33% of the women and 16.5% of the men. For each sex, the patients and controls exhibited the same proportion of complications. The most common symptom, dizziness, was attributable to methionine loading. In addition, isolated sleepiness, nausea, polyuria and decreased or increased blood pressure were observed in part of the subjects. None of the 887 individuals died within the 30-day period following the test...
Krupkova-Meixerova L et al; Clin Nutr 21 (2): 151-6 (2002).

8.7 Biomarker Information

9 Food Additives and Ingredients

9.1 Food Additive Classes

Flavoring Agents

9.2 FDA Substances Added to Food

Substance
Used for (Technical Effect)
FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, NUTRIENT SUPPLEMENT
Document Number (21 eCFR)

10 Pharmacology and Biochemistry

10.1 Pharmacodynamics

L-Methionine is a principle supplier of sulfur which prevents disorders of the hair, skin and nails; helps lower cholesterol levels by increasing the liver's production of lecithin; reduces liver fat and protects the kidneys; a natural chelating agent for heavy metals; regulates the formation of ammonia and creates ammonia-free urine which reduces bladder irritation; influences hair follicles and promotes hair growth. L-methionine may protect against the toxic effects of hepatotoxins, such as acetaminophen. Methionine may have antioxidant activity.

10.2 ATC Code

V - Various

V03 - All other therapeutic products

V03A - All other therapeutic products

V03AB - Antidotes

V03AB26 - Methionine

10.3 Bionecessity

Plays an important role in biological methylation. Both l- and d-forms are effective in rat and man. D-form undergoes deamination, and the keto compound is then transaminated with the resultant inversion of the natural l-form.
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 780
Methionine restriction (MR) limits age-related adiposity in Fischer 344 (F344) rats. To assess the mechanism of adiposity resistance, the effect of MR on adipose tissue (AT) 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1) was examined. MR induced 11beta-HSD1 activity in all ATs, correlating with increased tissue corticosterone. However, an inverse relationship between 11beta-HSD1 activity and adipocyte size was observed. Because dietary restriction controls lipogenic and lipolytic rates, MR's effects on lipogenic and lipolytic enzymes were evaluated. MR increased adipose triglyceride lipase and acetyl-coenzyme A carboxylase (ACC) protein levels but induced ACC phosphorylation at serine residues that render the enzyme inactive, suggesting alterations of basal lipolysis and lipogenesis. In contrast, no changes in basal or phosphorylated hormone-sensitive lipase levels were observed. ACC-phosphorylated sites were specific for AMP-activated protein kinase (AMPK); therefore, AMPK activation was evaluated. Significant differences in AMPKalpha protein, phosphorylation, and activity levels were observed only in retroperitoneal fat from MR rats. No differences in protein kinase A phosphorylation and intracellular cAMP levels were detected. In vitro studies revealed increased lipid degradation and a trend toward increased lipid synthesis, suggesting the presence of a futile cycle. In conclusion, MR disrupts the lipogenic/lipolytic balance, contributing importantly to adiposity resistance in F344 rats.
Perrone CE et al; J Lipid Res 49 (1): 12-23 (2008). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17909224
The methionine choline-deficient (MCD) diet results in liver injury similar to human nonalcoholic steatohepatitis (NASH). The aims of this study were to define mechanisms of MCD-induced steatosis in insulin-resistant db/db and insulin-sensitive db/m mice. MCD-fed db/db mice developed more hepatic steatosis and retained more insulin resistance than MCD-fed db/m mice. Both subcutaneous and gonadal fat were reduced by MCD feeding: gonadal fat decreased by 23% in db/db mice and by 90% in db/m mice. Weight loss was attenuated in the db/db mice, being only 13% compared with 35% in MCD-fed db/db and db/m mice, respectively. Both strains had upregulation of hepatic fatty acid transport proteins as well as increased hepatic uptake of [14C]oleic acid: 3-fold in db/m mice (P < 0.001) and 2-fold in db/db mice (P < 0.01) after 4 weeks of MCD feeding. In both murine strains, the MCD diet reduced triglyceride secretion and downregulated genes involved in triglyceride synthesis. Therefore, increased fatty acid uptake and decreased VLDL secretion represent two important mechanisms by which the MCD diet promotes intrahepatic lipid accumulation in this model...
Rinella ME et al; J Lipid Res 49 (5): 1068-76 (2008). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18227531
In women whose average daily intake of methionine was above the lowest quartile of intake (greater than 1.34 g/day), a 30 to 40% reduction in neural tube defect-affected pregnancies was observed. These reductions were observed for both anencephaly and spina bifida.
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. 726, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
For more Bionecessity (Complete) data for (L)-Methionine (20 total), please visit the HSDB record page.

10.4 Absorption, Distribution and Excretion

Absorption
Absorbed from the lumen of the small intestine into the enterocytes by an active transport process.
... Rats were fed diets containing [(14)C-methyl]l-methionine ... with 6% of sodium formate, and conversion of (14)C into [(14)C]formate was measured in urine and exhaled air (as (14)CO2) ... Total oxidation of [(14)C-methyl] into CO2, amounted to 60-87% for methionine ...
The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 5: A Review of the Literature Published during 1976 and 1977. London: The Chemical Society, 1979., p. 435
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
Protein secretion into the intestine continues even under conditions of protein-free feeding, and fecal nitrogen losses (ie, nitrogen lost as bacteria in the feces) may account for 25% of the obligatory loss of nitrogen. Under this dietary circumstance, the amino acids secreted into the intestine as components of proteolytic enzymes and from sloughed mucosal cells are the only sources of amino acids for the maintenance of the intestinal bacterial biomass. ... Other routes of loss of intact amino acids are via the urine and through skin and hair loss. These losses are small by comparison with those described above, but nonetheless may have a significant impact on estimates of requirements, especially in disease states. /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. 600-601, 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)-Methionine (11 total), please visit the HSDB record page.

10.5 Metabolism / Metabolites

Hepatic
Product of oxidative deamination or transamination--alpha-keto-gamma-methiolbutyric acid. /From table/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 831
... Oxidation of methionine (S-methyl-l-cysteine and sarcosine) methyl group in vivo proceeds primarily by way of free formate, and that conversion to formate is probably not catalysed by tetrahydrofolic acid.
The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 5: A Review of the Literature Published during 1976 and 1977. London: The Chemical Society, 1979., p. 435
... Methionine ... is catabolized to a large extent independently of initial activation to S-adenosyl-l-methionine. The system for catabolism ... appears analogous to one that catalyses oxidation of S-methyl-l-cysteine methyl group ... The methyl group of methionine ... /has been/ shown ... to yield formate in vitro and in vivo.
The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 5: A Review of the Literature Published during 1976 and 1977. London: The Chemical Society, 1979., p. 435
Infants more rapidly metabolized methionine than adults.
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. 726, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
For more Metabolism/Metabolites (Complete) data for (L)-Methionine (7 total), please visit the HSDB record page.

10.6 Mechanism of Action

The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.
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
Methionine dependence, the inability of cells to grow when the amino acid methionine is replaced in culture medium by its metabolic precursor homocysteine, is characteristic of many cancer cell lines and some tumors in situ. Most cell lines proliferate normally under these conditions. The methionine dependent tumorigenic human melanoma cell line MeWo-LC1 was derived from the methionine independent non-tumorigenic line, MeWo. MeWo-LC1 has a cellular phenotype identical to that of cells from patients with the cblC inborn error of cobalamin metabolism, with decreased synthesis of cobalamin coenzymes and decreased activity of the cobalamin-dependent enzymes methionine synthase and methylmalonylCoA mutase. Inability of cblC cells to complement the defect in MeWo-LC1 suggested that it was caused by decreased activity of the MMACHC gene. However, no potentially disease causing mutations were detected in the coding sequence of MMACHC in MeWo-LC1. No MMACHC expression was detected in MeWo-LC1 by quantitative or non-quantitative PCR. There was virtually complete methylation of a CpG island at the 5'-end of the MMACHC gene in MeWo-LC1, consistent with inactivation of the gene by methylation. The CpG island was partially methylated (30-45%) in MeWo and only lightly methylated (2-11%) in control fibroblasts. Infection of MeWo-LC1 with wild type MMACHC resulted in correction of the defect in cobalamin metabolism and restoration of the ability of cells to grow in medium containing homocysteine. /It was concluded/ that epigenetic inactivation of the MMACHC gene is responsible for methionine dependence in MeWo-LC1.
Loewy AD et al; Mol Genet Metab 96 (4): 261-7 (2009). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19200761

10.7 Human Metabolite Information

10.7.1 Tissue Locations

  • Fibroblasts
  • Kidney
  • Liver
  • Pancreas
  • Placenta
  • Prostate
  • Skeletal Muscle
  • Spleen

10.7.2 Cellular Locations

Extracellular

10.7.3 Metabolite Pathways

10.8 Biochemical Reactions

11 Use and Manufacturing

11.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: Methionine
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; Used therapeutically as an antidote for acetaminophen poisoning and a urinary acidifier; [Merck Index] Chelating agent for heavy metals; [ChemIDplus] Used as a flavoring agent and nutritional supplement for foods; [FDA] Used in pharmaceuticals, as a feed additive, for vegetable oil enrichment, and as single cell protein; [NTP] Permitted for use as an inert ingredient in non-food pesticide products; [EPA]
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.
Industrial Processes with risk of exposure
Farming (Feed Additives) [Category: Industry]
Feed additive; vegetable oil enrichment; single-cell protein /DL-Methionine/
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 752
Nutrient
FCC; Food Chemicals Codex. Committee on Food Chemicals Codex, Food and Nutrition Board, Institute of Medicine. 5th. Washington, DC: National Academy Press p. 286 (2003)
BIOLOGICAL ACTIVITIES: Anticataract; antidote (acteaminophen, paracetamol); antieczemic; antihepatotic; antioxidant; antiparkinsonian; cancer-preventive; emetic; essential; glutathionigenic; heptoprotective; lioptropic; urine-acidifier, urine-deodorant
USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Methionine. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of August 17, 2010: https://www.ars-grin.gov/duke/
THERAPEUTIC CATEGORY: Hepatoprotectant; antidote (acetaminophen poisoning); urinary acidifier
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1032
For more Uses (Complete) data for (L)-Methionine (6 total), please visit the HSDB record page.

Use (kg; approx.) in Germany (2009): >25000

Consumption (g per capita; approx.) in Germany (2009): 0.305

Calculated removal (%): 92.1

Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.

11.1.1 Use Classification

EPA Safer Chemical Functional Use Classes -> Enzymes and Enzyme Stabilizers
Safer Chemical Classes -> Green circle Green circle - The chemical has been verified to be of low concern
EPA Safer Chemical Functional Use Classes -> Skin Conditioning Agents
Safer Chemical Classes -> Green half-circle Green half-circle - The chemical is expected to be of low concern
Food additives -> Flavoring Agents
Cosmetics -> Antistatic; Hair conditioning; Skin conditioning
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 5 consumer products that contain Methionine in the following categories is provided:

• Personal Care

11.2 Methods of Manufacturing

The production method of choice for L-methionine is still the enzymatic resolution of racemic N-acetyl-methionine using acylase from Aspergillus oryzae. The production is carried out in a continuously operated fixed-bed or enzyme membrane reactor. Alternatively, L-methionine may be produced by microbial conversion of the corresponding 5-substituted hydantoin. With growing cells of Pseudomonas sp. strain NS671, D,L-5-(2-methylthioethyl)hydantoin was converted to L-methionine; a final concentration of 34 g/L and a molar yield of 93% have been obtained.
Eggersdorfer M et al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (2008). New York, NY: John Wiley & Sons; Vitamins. Online Posting Date: June 15, 2000
The most economic way for production of D,L-methionine is the chemical process based on acrolein, methyl mercaptan, hydrogen cyanide, and ammonium carbonate. beta-Methylthiopropionaldehyde, formed by addition of methyl mercaptan to acrolein, is the intermediate that reacts with hydrogen cyanide to give alpha-hydroxy-gamma-methylthiobutyronitrile. Treatment with ammonium carbonate leads to 5-(beta-methylthioethyl)hydantoin that is saponified by potassium carbonate giving D,L-methionine in up to 95% yield, calculated on acrolein. /D,L-Methionine/
Eggersdorfer M et al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (2008). New York, NY: John Wiley & Sons; Vitamins. Online Posting Date: June 15, 2000

11.3 Formulations / Preparations

NF, feed 98%
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 752
USP and FCC grades; 99% feed grade
Kuney, J.H., J.M. Mullican (eds.). Chemcyclopedia. Washington, DC: American Chemical Society, 1994., p. 286
Racemate mixture of D- and L- methionine
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA2: 71 (1985)

11.4 Consumption Patterns

Used almost exclusively to improve the nutritive value of animal feeds /DL-Methionine/
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA2: 91 (1985)

11.5 U.S. Production

Aggregated Product Volume

2018: <1,000,000 lb

2017: <1,000,000 lb

2016: <1,000,000 lb

(1992) No data
United States International Trade Commission. Synthetic Organic Chemicals - United States Production and Sales, 1992. USITC Publication 2720, Feb. 1994 Washington, D.C.: United States Trade Commission, 1994.
World market for L-methionine in 1982: 150 tons; World market for DL-methionine in 1982: 110,000 tons
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA2: 90 (1985)
Production volumes for non-confidential chemicals reported under the Inventory Update Rule.
Year
1986
Production Range (pounds)
10 thousand - 500 thousand
Year
1990
Production Range (pounds)
No Reports
Year
1994
Production Range (pounds)
No Reports
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-Methionine (63-68-3). Available from, as of March 23, 2010: https://www.epa.gov/oppt/iur/tools/data/2002-vol.html

11.6 General Manufacturing Information

EPA TSCA Commercial Activity Status
Methionine: ACTIVE
EPA TSCA Commercial Activity Status
L-Methionine: ACTIVE
... Available as d,l-methionine and as calcium salt of hydroxy analog of methionine. These products are used ... in animal feeds ... Relative biological value of these compared to l-methionine ... evidence suggests equivalency on mole basis both in rats and man.
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 109
The D-form of methionine is as equally nutritive as the L-form, so that DL-methionine which is inexpensively produced by the chemical synthesis is primarily used as a feed supplement
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V2: 556 (1992)
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: methionine; Matrix: vitamin preparations; Detection Limit: not provided.
Official Methods of Analysis of AOAC International, 18th Edition Online. Methionine (63-68-3). 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: methionine; Matrix: feeds; Detection Limit: not provided.
Official Methods of Analysis of AOAC International, 18th Edition Online. Methionine (63-68-3). Available from, as of March 25, 2010: https://www.aoac.org
Method: AOAC 999.13; Procedure: high performance liquid chromatography post-column derivatization; Analyte: methionine; 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. Methionine (63-68-3). Available from, as of March 25, 2010: https://www.aoac.org
SIMPLE PROCEDURE IN WHICH SILVER LIGAND CHROMATOGRAPHY IS USED TO ISOLATE METHIONINE FROM AMINO ACID MIXTURES IS DESCRIBED.
SHAW DC, WEST CE; J CHROMATOGR 200(0) 185 (1980)
The following methods have been developed for the analysis of free amino acids in blood, food, and feedstocks: (1) Protein hydrolysis, (2) Chromatographic methods that include high performance liquid chromatography (HPLC), gas chromatography (GC) and thin-layer chromatography (TLC), (3) Colorimetric and Fluorimetric Analysis, (4) Spectrometric Analysis, and (5) Enzymatic Determination and Microbial Assay /amino acids/
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V2 531-4

12.2 Clinical Laboratory Methods

GC-MS determination in biological fluids
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1032

13 Safety and Hazards

13.1 Hazards Identification

13.1.1 GHS Classification

Note
This chemical does not meet GHS hazard criteria for 97.6% (206 of 211) of all reports. Pictograms displayed are for 2.4% (5 of 211) of reports that indicate hazard statements.
GHS Hazard Statements

Not Classified

Reported as not meeting GHS hazard criteria by 206 of 211 companies (only 2.4% companies provided GHS information). For more detailed information, please visit ECHA C&L website.

ECHA C&L Notifications Summary

Aggregated GHS information provided per 211 reports by companies from 7 notifications to the ECHA C&L Inventory.

Reported as not meeting GHS hazard criteria per 206 of 211 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 5 notifications provided by 5 of 211 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 EPA Safer Chemical

Chemical: DL-Methionine

Green circle Green circle - The chemical has been verified to be of low concern based on experimental and modeled data.

Chemical: L-Methionine

Green half-circle Green half-circle - The chemical is expected to be of low concern based on experimental and modeled data. Additional data would strengthen EPA's confidence in the chemical's safer status.

13.1.4 Health Hazards

ACUTE/CHRONIC HAZARDS: This material is dangerous when heated to decomposition; it emits dangerous and highly toxic fumes. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.1.5 Fire Hazards

Flash point data for this material is not available, but it is probably combustible. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.1.6 Hazards Summary

Reacts with water evolving hydrogen sulfide (toxic and flammable); [CAMEO] May cause irritation; [Sigma-Aldrich MSDS] See Hydrogen sulfide.

13.2 First Aid Measures

13.2.1 First Aid

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.3 Fire Fighting

Fires involving this material can be controlled using a CO2, foam, and/or Halon extinguisher. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.4 Accidental Release Measures

13.4.1 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.

13.5 Handling and Storage

13.5.1 Nonfire Spill Response

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should keep this material in a tightly-closed container under an inert atmosphere, and store it at refrigerated temperatures. (NTP, 1992)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.6 Exposure Control and Personal Protection

13.6.1 Personal Protective Equipment (PPE)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.7 Stability and Reactivity

13.7.1 Air and Water Reactions

Reacts with water, steam, and/or acids to produce toxic and flammable vapors of hydrogen sulfide (NTP, 1992). Water soluble (NTP, 1992). pH of 1% aqueous solution is 5.6-6.0.
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.7.2 Reactive Group

Sulfides, Organic

Salts, Acidic

13.7.3 Reactivity Profile

An organosulfide and amine derivative, carboxylic acid. Look at Reactive Groups 20 (organosulfides), 7 (amines), and 3 (carboxylic acids) may give indications about reactive tendencies. It is an amino acid essential in human nutrition.

13.8 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: L-Methionine
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Methionine: Does not have an individual approval but may be used under an appropriate group standard
New Zealand EPA Inventory of Chemical Status
L-Methionine: Does not have an individual approval but may be used under an appropriate group standard

13.8.1 FDA Requirements

L-Methionine 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: methionine 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
Methionine 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 582.5475 (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

13.9 Other Safety Information

Chemical Assessment

IMAP assessments - L-Methionine: Environment tier I assessment

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

13.9.1 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

The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.

14.1.2 Drug Induced Liver Injury

Compound
l-methionine
DILI Annotation
No-DILI-Concern
Label Section
No match
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

14.1.3 Carcinogen Classification

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

14.1.4 Health Effects

Chronically high levels of methionine are associated with at least 7 inborn errors of metabolism including: Cystathionine Beta-Synthase Deficiency, Glycine N-methyltransferase Deficiency, Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, Methionine Adenosyltransferase Deficiency, Methylenetetrahydrofolate reductase deficiency and S-Adenosylhomocysteine (SAH) Hydrolase Deficiency.

14.1.5 Exposure Routes

Absorbed from the lumen of the small intestine into the enterocytes by an active transport process.

14.1.6 Acute Effects

14.1.7 Interactions

The adverse effects of methionine are alleviated by supplements of glycine or serine ... Vit B6 deficiency reduces the tolerance of the rat for methionine.
Toxicants Occurring Naturally In Foods, 2nd Ed NAS/NRC Wash DC, 134 (1973)
Pretreatment of young male rats with excess retinol (800 IU/g diet for 10 days) partially counteracted the adverse effects caused by a high methionine intake.
Peng Y-S et al; Nutr Rep Int 23(2) 303 (1981)
Methionine provided in the drinking water of pregnant rats injected with sodium valproate reduced the frequency of resorptions but did not improve embryo growth. Rats drinking methionine supplemented water had approx twice the level of serum free methionine and consumed only one half the volume of water as controls. Using whole rat embryo cultures, the simultaneous addition of methionine and sodium valproate to the medium provided no protection from the teratogenic effects of sodium valproate ... Protection from the teratogenic effects of sodium valproate was afforded by methionine and was particularly striking when embryos for culture were taken from pregnant rats that had been consuming methionine.
Nosel PG, Klein NW; Teratology 46 (5): 499-507 (1992).
This study showed that short-term vitamin administration /(folic acid, vitamins B6 and B12)/ effectively reduced post-methionine load homocysteine levels and thereby ameliorated endothelium-dependent flow-mediated vasodilation in 16 healthy adults. Post-methionine load homocysteine levels decreased from 22.7+/-3.8 to 17.0+/-2.1 micromol/L (p <0.001), and flow-mediated vasodilation after methionine load increased from 8.6+/-3.6% to 13.8+/-2.9% (p <0.001) after vitamin administration.
Chao CL et al; Am J Cardiol 84 (11): 1359-61, A8 (1999).
For more Interactions (Complete) data for (L)-Methionine (18 total), please visit the HSDB record page.

14.1.8 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

14.1.9 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ Methionine was administered to 17 adults with liver disease 8-20 g/day in divided doses for 3-9 days. In 7 patients with portal cirrhosis, neurological deterioration occurred from 1-4 days after total doses of 11-46 g. Methionine was tolerated in 10 controls.
Toxicants Occurring Naturally In Foods, 2nd Ed NAS/NRC Wash DC: 141 (1973)
/HUMAN EXPOSURE STUDIES/ Oral methionine supplements (8.0 g daily for 4 days) were given to five normal volunteers who continued to eat their usual diet. This treatment resulted in a significant fall in serum folate concentration. Three days after the end of treatment concentrations had not completely returned to control values. The fall in concentration was prevented by giving oral folic acid supplements.
Connor H; Postgrad med J 54 (631): 318-20 (1978).
/HUMAN EXPOSURE STUDIES/ ... The aim of the study was to investigate if methionine supplementation causes changes in endothelial function, plasma homocysteine, or lipid peroxidation which may be associated with atherosclerosis. Sixteen healthy volunteers were studied. Forearm blood flow in response to local intra-arterial infusion of acetylcholine to assess endothelium-dependent vasodilatation and sodium nitroprusside to assess endothelium-independent vasodilatation was measured by venous occlusion plethysmography. Plasma homocysteine and lipid peroxidation, measured as thiobarbituric acid reactive substances, were measured using high-performance liquid chromatography. Forearm vascular responses, plasma homocysteine concentrations, and thiobarbituric acid reactive substances were measured at baseline and following methionine supplementation. RESULTS: There was no significant difference in endothelial-dependent vascular responses after acute (methionine 250 mg orally, p > 0.05), 1 month of low-dose (methionine 250 mg daily, p > 0.05), or 1 week of high-dose (methionine 100 mg/kg daily, p > 0.05) methionine administration. There was no significant difference in plasma homocysteine concentrations after acute (p > 0.05) or 1 month of low-dose (p > 0.05) methionine administration. However, 1 week of high-dose methionine (100 mg/kg) administration daily significantly increased homocysteine concentrations (p < 0.0015). Thiobarbituric acid reactive substances were unchanged during the period of study (p > 0.05)...
McAuley DF et al; J Toxicol Clin Toxicol 37 (4): 435-40 (1999).
/HUMAN EXPOSURE STUDIES/ Prolonged exposure to nitrous oxide causes adverse effects mimicking those of cobalamin deficiency. This is explained by irreversible oxidation of cobalamin bound to the enzyme methionine synthase. The inactivation of methionine synthase by nitrous oxide in cultured human fibroblasts is decreased at high concentrations of methionine in culture medium. ... The possible protection against cobalamin inactivation by preoperative methionine loading /was investigated/ in patients undergoing nitrous oxide anesthesia. Fourteen patients receiving anesthesia for 75-230 min were included. Half of these patients received a peroral methionine loading dose 2 hr before anesthesia. After nitrous oxide exposure, a considerable inactivation of methionine synthase in mononuclear white blood cells was seen in all patients, reaching a nadir after 5-48 hr. In the patients not subjected to a methionine load, recovery of enzyme activity was not complete within 7 days. In the patients receiving a methionine load, the kinetics of inactivation of methionine synthase were similar, but the rate and extent of enzyme recovery was higher than in patients not receiving methionine, and in four patients, the enzyme activity even exceeded the preoperative level. The inactivation of methionine synthase was associated with a transient increase in plasma homocysteine, and the homocysteine concentration was still increased (mean 28.7%) 7 days after anesthesia in the patients not receiving methionine. A marked peak in homocysteine concentration was observed immediately after anesthesia in the methionine-loaded patients, but the homocysteine level was still increased (mean of 30.5%) after 7 days. The activity of the other cobalamin-dependent enzyme, methylmalonyl coenzyme A mutase, in the mononuclear white blood cells, and the serum concentration of the cobalamin marker methylmalonic acid, were not altered after nitrous oxide anesthesia or methionine loading or both...
Christensen B et al; Anesthesiology 80 (5): 1046-56 (1994).
For more Human Toxicity Excerpts (Complete) data for (L)-Methionine (19 total), please visit the HSDB record page.

14.1.10 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ A single dietary dose (2.7% of the diet) of L-methionine decreased body growth and also reduced food intake in rats.
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. 725, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Feeding excess dietary DL-methionine to broiler chicks at 1.5% significantly depressed (p < 0.01) gain in body wt, hematocrit, and hemoglobin concentrations, increased (p < 0.05) iron level in liver and spleen, caused pancreatic damage and neurological changes.
Ekperigin HE, Vohra P; Avian Dis 25(1) 82 (1981).
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Dietary excesses of L-methionine (2.7% of the diet) for 6, 13, or 20 days have been associated with erythrocyte engorgement and accumulation of hemosiderine in rats, and there was a depression of growth and splenic damage.
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. 725, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Dietary intakes of 2 to 4% of L-methionine caused slight changes in liver cells in rats and slight decreases in liver iron content. Darkened spleens caused by increases in iron deposition have been observed in weanling rats fed 1.8% methionine diets for 28 days.
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. 725, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
For more Non-Human Toxicity Excerpts (Complete) data for (L)-Methionine (18 total), please visit the HSDB record page.

14.1.11 Non-Human Toxicity Values

LD50 Rat oral 36,000 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. 2334
LD50 Rat ip 4238 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. 2334

14.1.12 Populations at Special Risk

This case-controlled, monocenter association study included 290 patients of Caucasian origin undergoing surgical resection for intracranial meningioma (World Health Organization [WHO] Grade I, 190 cases; WHO Grade II, 82 cases; WHO Grade III, 18 cases) and 287 age- and sex-matched local controls. The authors analyzed the following genetic variants: dihydrofolate reductase c.594+59del19, 5,10-methylenetetrahydrofolate reductase c.677C > T and c.1298A > C, 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR) c.2756A > G, reduced folate carrier 1 c.80G > A, cystathionine beta-synthase (CBS) c.844_855ins68 and transcobalamin 2 c.776C > G. RESULTS: The variant CBS c.844_855ins68 -- that is, the allele carrying the insertion ("ins" or "i") as opposed to the wild-type allele designated as deletion ("del" or "d") -- was significantly overrepresented in meningioma patients (dd/ id/ii: 0.81/0.18/0.01) in comparison with the controls (dd/id/ii: 0.88/0.12/0; 2 df, chi-square 8.97, p = 0.011; multiple nominal regression with age and sex as covariables). In addition, explorative analyses revealed an association of the MTR c.2756A > G variant with meningioma WHO Grade III (AA/AG/GG: patients, 1.0/0/0; controls, 0.64/0.32/0.04; 2 df, chi-square 14.44, p = 0.001). CONCLUSIONS: The results of this study suggest that genetic variants of methionine metabolism are associated with meningioma formation.
Semmler A et al; J Neurosurg 108 (5): 999-1004 (2008). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18447718

14.2 Ecological Information

14.2.1 Ecotoxicity Values

LC50; Species: Eisenia fetida (earthworm, mature, weight 370-450 mg) direct application using filter paper >1000 AI ug/sq cm for 48 hr
Roberts BL, Dorough HW; Environ Toxicol Chem 3 (1): 67-78 (1984) as cited in the ECOTOX database. Available from, as of December 31, 2009

14.2.2 Environmental Fate / Exposure Summary

(L)-Methionine's production and use as a nutritional supplement in animal feeds may result in its release to the environment through various waste streams. (L)-Methionine is formed in natural waters through metabolism of naturally occurring proteins and is a naturally occurring amino acid, being present in foods such as maize, rice, wheat, potato, soybeans, lettuce, apples, oranges, beef, fish, milk, cheese and eggs. If released to air, an estimated vapor pressure of 8.1X10-8 mm Hg at 25 °C indicates (L)-methionine will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase (L)-methionine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 7.5 hours. Particulate-phase (L)-methionine will be removed from the atmosphere by wet or dry deposition. (L)-Methionine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, (L)-methionine is expected to have very high mobility based upon an estimated Koc of 8. The pKa values of (L)-methionine are 2.28 and 9.21, which indicate that this compound will exist as a zwitterion which may affect its adsorption to soils and sediments. Volatilization from moist soil is not expected because ions do not volatilize. (L)-Methionine may not volatilize from dry soil surfaces based upon its vapor pressure. Using a laboratory activated sludge system, (L)-methionine exhibited an 80% theoretical BOD reduction in 16 days, producing 3-mercaptopropionate, methanethiol and dimethylsulfide; this suggests that biodegradation may be an important environmental fate process. If released into water, (L)-methionine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. The pKa values of 2.28 and 9.21 indicate (L)-methionine will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. (L)-Methionine has been shown to degrade in sunlit natural water through photo-sensitized oxidation involving singlet oxygen. Occupational exposure to (L)-methionine may occur through inhalation and dermal contact with this compound at workplaces where (L)-methionine is produced or used. Monitoring data indicate that the general population may be exposed to (L)-methionine via ingestion of food. (SRC)

14.2.3 Natural Pollution Sources

(L)-Methionine is formed in natural waters through metabolism of naturally occurring proteins(1). It 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(2). (L)-Methionine is a naturally occurring amino acid constituent of egg albumin, casein, and beta-lactoglobulin proteins(3); (L)-methionine occurs naturally in foods such as maize, rice, wheat, potato, soybeans, lettuce, bean, tomato, apples, oranges, beef, veal, fish, milk, cheese and eggs(3).
(1) Kiene RP, Visscher PT; Appl Environ Microbiol 53: 2426-34 (1987)
(2) 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
(3) Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.

14.2.4 Artificial Pollution Sources

(L)-Methionine's production and use as nutritional supplement in animal feeds(1) may result in its release to the environment through various waste streams(SRC).
(1) Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.

14.2.5 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8(SRC), determined from a log Kow of -1.87(2) and a regression-derived equation(3), indicates that (L)-methionine is expected to have very high mobility in soil(SRC). The pKa values of (L)-methionine are 2.28 and 9.21(4), indicate that this compound will exist as a zwitterion which may affect its adsorption to soils and sediments(SRC). Volatilization from moist soil is not expected because ions do not volatilize(SRC). (L)-Methionine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.1X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Using a laboratory activated sludge system, (L)-methionine exhibited an 80% theoretical BOD reduction in 16 days, producing 3-mercaptopropionate, methanethiol and dimethylsulfide(6); this suggests that biodegradation may be an important environmental fate process in soil(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 15 (1995)
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Feb 19, 2010.
(4) Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.
(5) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(6) Engelbrecht RS, McKinney RE; Sew Indust Wastes 29: 1350-62 (1957)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8(SRC), determined from a log Kow of -1.87(2) and a regression-derived equation(3), indicates that (L)-methionine is not expected to adsorb to suspended solids and sediment(SRC). The pKa values of 2.28 and 9.21(4) indicates (L)-methionine will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Using a laboratory activated sludge system, (L)-methionine exhibited an 80% theoretical BOD reduction in 16 days, producing 3-mercaptopropionate, methanethiol and dimethylsulfide(8); this suggests that biodegradation may be an important environmental fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 15 (1995)
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Feb 19, 2010.
(4) Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.
(5) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds, Boca Raton, FL: Lewis Publ (2000)
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(8) Engelbrecht RS, McKinney RE; Sew Indust Wastes 29: 1350-62 (1957)
AQUATIC FATE: (L)-Methionine has been shown to degrade in sunlit natural water through a photo-sensitized oxidation involving singlet oxygen(1,2); assuming that the top meter of sunlit natural water has a singlet oxygen concn of 4X10-14 M, the photooxidation half-life for the reaction (L)-methionine with singlet oxygen has been estimated to be about 200 hr at pH 6-11(1); the near-surface photooxidation rate (via singlet oxygen) of (L)-methionine in Okefenokee Swamp water from Georgia is predicted to be about 3 hr(2). Bioconcentration and volatilization are not expected to important fate processes because of its high water solubility(SRC).
(1) Haag WR, Holgne J; Environ Sci Technol 20: 341-8 (1986)
(2) Zepp RG et al; Nature 267: 421-3 (1977)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), (L)-methionine, which has an estimated vapor pressure of 8.1X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase (L)-methionine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 7.5 hours(SRC), calculated from its rate constant of 5.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). (L)-Methionine does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

14.2.6 Environmental Biodegradation

AEROBIC: In a laboratory activated sludge system, (L)-methionine had an 80% theoretical BOD reduction after 16 days of incubation(1). In a Warburg respirometer study using activated sludge, (L)-methionine (at a concn of 500 mg/L) had a theoretical BOD of 2.6% over a 24-hr incubation period(2). In an activated sludge system that had been acclimated to phenol, (L)-methionine had a theoretical oxidation of 16% after 12 hrs of aeration(3).
(1) Engelbrecht RS, McKinney RE; Sew Indust Wastes 29: 1350-62 (1957)
(2) Malaney GW, Gerhold RM; J Water Pollut Control Fed 41: R18-R33 (1969)
(3) McKinney RE et al; Sew Indust Wastes 28: 547-57 (1956)
ANAEROBIC: The biotransformation of (L)-methionine in anoxic sediment slurries was found to produce 3-mercaptopropionate(1). In salt marsh sediment slurries, microbial metabolism of (L)-methionine yielded methanethiol as the major volatile organosulfur product, with the formation of lesser amounts of dimethylsulfide(2); the decomposition of (L)-methionine occurred rapidly in anoxic salt marsh sediments(2). (L)-Methionine was highly bioconvertible (68-90% CO2 evolution) in 35-78 day anaerobic degradation studies using waste activated sludge from the San Jose-Santa Clara Water Pollution Control Plant(3).
(1) Kiene RP, Taylor BF; Nature 332: 148-50 (1988)
(2) Kiene RP, Visscher PT; Appl Environ Microbiol 53: 2426-34 (1987)
(3) Stuckey DC, McCarty PL; Water Res 18: 1343-53 (1984)

14.2.7 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of (L)-methionine with photochemically-produced hydroxyl radicals has been estimated as 6.1X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 7.5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). (L)-Methionine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). (L)-Methionine does not contain chromophores that absorb at wavelengths >290 nm(3) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)

14.2.8 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for (L)-methionine(SRC), using a log Kow of -1.87(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 125 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Feb 19, 2010.
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

14.2.9 Soil Adsorption / Mobility

The Koc of (L)-methionine is estimated as 8(SRC), using a log Kow of -1.87(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that (L)-methionine is expected to have very mobility in soil. The pKa values of (L)-methionine are 2.28 and 9.21(4), indicate that this compound will exist as a zwitterion which may affect its adsorption to soils and sediments(SRC). One study found that (L)-methionine was one of many amino acids that sorbed to carbonate sediments in seawater(5); a positive correlation between surface area (of the sediment) and the amount of sorbed amino acids indicated that sorption from solution (partitioning from the water column to sediment) was a likely mechanism(5).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 15 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Feb 19, 2010.
(3) Swann RL et al; Res Rev 85: 17-28 (1983)
(4) Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.
(5) Muller PJ, Suess E; Geochim Casmochim Acta 41: 941-9 (1977)

14.2.10 Volatilization from Water / Soil

The pKa values of 2.28 and 9.21(1) indicate (L)-methionine will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(2). (L)-Methionine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.1X10-8 mm Hg(SRC), determined from a fragment constant method(3).
(1) Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.
(2) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(3) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

14.2.11 Sediment / Soil Concentrations

SOIL: (L)-Methionine concentrations in three soil horizons of an active landfill, the Conica Montemarte outside of Seville, Spain, were reported as 0.5 nmol/g (1.0-1.5 meters), 19.9 nmol/g (3.0-3.5 meters), and 38.2 nmol/g (6.5-7.0 meters), 6, 18, and 24 months after deposition respectively(1).
(1) Gonzalez-Vila, FJ et al; Chemosphere 31: 2817-25 (1995)
SEDIMENT: (L)-Methionine concentrations of 0.46 to 0.055 umol/g were detected in carbonate sediment samples collected from a lagoon of Fanning Island, an atoll in the Line Islands of the Central Pacific Ocean(1).
(1) Muller PJ, Suess E; Geochim Casmochim Acta 41: 941-9 (1977)

14.2.12 Food Survey Values

The average methionine content of some foodstuffs (in mg/100g) has been reported as follows: maize, grain: 182; rice, husked: 183; wheat, whole grain: 196; potato: 26; bean (Phaselous vulgaris): 234; soybean, milk: 50; soy protein, isolate: 1008; tomato: 7; apple: 3; orange: 12; beef, veal, edible flesh: 478; fish: 220; cheese: 530; egg, whole: 416(1).
(1) Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.

14.2.13 Plant Concentrations

Plants with the highest amount of Methionine(1).
Genus species
Helianthus annuus L.
Commone name(s)
Girasol, Sunflower
Concentration
5,220 - 20,500 ppm
Area of Plant
Seed
Genus species
Cucurbita foetidissima HBK.
Commone name(s)
Buffalo Gourd
Concentration
2,610 - 19,000 ppm
Area of Plant
Seed
Genus species
Nigella sativa L.
Commone name(s)
Black Caraway, Black Cumin, Fennel-Flower, Nutmeg-Flower, Roman Coriander
Concentration
13,100 - 16,750 ppm
Area of Plant
Seed
Genus species
Bertholletia excelsa BONPL.
Commone name(s)
Brazilnut, Brazilnut-Tree, Creamnut, Paranut
Concentration
10,140 - 10,346 ppm
Area of Plant
Seed
Genus species
Sesamum indicum L.
Commone name(s)
Ajonjoli (Sp.), Beni, Benneseed, Sesame, Sesamo (Sp.)
Concentration
3,120 - 9,413 ppm
Area of Plant
Seed
Genus species
Trigonella foenum-graecum L.
Commone name(s)
Alholva (Sp.), Bockshornklee (Ger.), Fenugreek, Greek Clover, Greek Hay
Concentration
120 - 8,830 ppm
Area of Plant
Leaf
Genus species
Juglans cinerea L.
Commone name(s)
Butternut
Concentration
6,111 - 6,321 ppm
Area of Plant
Seed
Genus species
Spinacia oleracea L.
Commone name(s)
Spinach
Concentration
530 - 6,294 ppm
Area of Plant
Plant
Genus species
Pinus pinea L.
Commone name(s)
Italian Stone Pine, Pignolia
Concentration
4,300 - 6,050 ppm
Area of Plant
Seed
Genus species
Cucurbita pepo L.
Commone name(s)
Pumpkin
Concentration
5,510 - 5,920 ppm
Area of Plant
Seed
Genus species
Ipomoea aquatica FORSSKAL
Commone name(s)
Swamp Cabbage, Water Spinach
Concentration
440 - 5,845 ppm
Area of Plant
Leaf
Genus species
Moringa oleifera LAM.
Commone name(s)
Ben Nut, Benzolive Tree, Drumstick Tree, Horseradish Tree, Jacinto (Sp.), Moringa, West Indian Ben
Concentration
1,230 - 5,765 ppm
Area of Plant
Shoot
Genus species
Oenothera biennis L.
Commone name(s)
Evening-Primrose
Concentration
5,400 - 5,763 ppm
Area of Plant
Seed
Genus species
Citrullus lanatus (THUNB.) MATSUM. &amp; NAKAI
Commone name(s)
Watermelon
Concentration
5,742 ppm
Area of Plant
Seed
Genus species
Colocasia esculenta (L.) SCHOTT
Commone name(s)
Taro
Concentration
790 - 5,510 ppm
Area of Plant
Leaf
Genus species
Glycine max (L.) MERR.
Commone name(s)
Soybean
Concentration
4,920 - 5,380 ppm
Area of Plant
Seed
Genus species
Corchorus olitorius L.
Commone name(s)
Jew's Mallow, Mulukiya, Nalta Jute
Concentration
460 - 5,290 ppm
Area of Plant
Leaf
Genus species
Sinapis alba L.
Commone name(s)
White Mustard
Concentration
4,800 - 5,136 ppm
Area of Plant
Seed
Genus species
Papaver bracteatum L.
Commone name(s)
Great Scarlet Poppy
Concentration
4,500 - 5,050 ppm
Area of Plant
Seed
Genus species
Papaver somniferum L.
Commone name(s)
Opium Poppy, Poppyseed Poppy
Concentration
4,700 - 5,042 ppm
Area of Plant
Seed
Genus species
Opuntia ficus-indica (L.) MILL.
Commone name(s)
Indian Fig, Nopal, Nopalito, Prickly Pear
Concentration
4,830 ppm
Area of Plant
Seed
Genus species
Phaseolus vulgaris subsp. var. vulgaris
Commone 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
440 - 4,731 ppm
Area of Plant
Sprout Seedling
Genus species
Ceratonia siliqua L.
Commone name(s)
Carob, Locust Bean, St.John's-Bread
Concentration
4,700 ppm
Area of Plant
Seed
Genus species
Amaranthus sp.
Commone name(s)
Pigweed
Concentration
360 - 4,331 ppm
Area of Plant
Leaf
Genus species
Avena sativa L.
Commone name(s)
Oats
Concentration
1,000 - 4,000 ppm
Area of Plant
Seed
Genus species
Hordeum vulgare L.
Commone name(s)
Barley, Barleygrass
Concentration
1,000 - 4,000 ppm
Area of Plant
Seed
Genus species
Nasturtium officinale R. BR.
Commone name(s)
Berro, Watercress
Concentration
200 - 4,000 ppm
Area of Plant
Herb
Genus species
Triticum aestivum L.
Commone name(s)
Wheat
Concentration
1,000 - 4,000 ppm
Area of Plant
Seed
Genus species
Mucuna pruriens (L.) DC.
Commone name(s)
Cowage, Velvetbean
Concentration
1,875 - 3,975 ppm
Area of Plant
Seed
Genus species
Pistacia vera L.
Commone name(s)
Pistachio
Concentration
3,810 - 3,963 ppm
Area of Plant
Seed
(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Methionine. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of August 17, 2010: https://www.ars-grin.gov/duke/

14.2.14 Animal Concentrations

Zebra mussels and clams sampled in November 1991 from Oneida Lake in NY State were found to have (L)-methionine levels of 1.66 and 1.58 g/100 g dry wt, respectively(1).
(1) Secor CL et al; Chemosphere 26: 1559-75 (1993)

14.2.15 Milk Concentrations

ENVIRONMENTAL: The average (L)-methionine content of cows milk is reported as 86 mg/100 g(1). The average (L)-methionine content of human milk is reported as 19 mg/100 g(1).
(1) Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.

14.2.16 Probable Routes of Human Exposure

NIOSH (NOES Survey 1981-1983) has statistically estimated that 28,250 workers (17,038 of these were female) were potentially exposed to (L)-methionine in the US(1). Occupational exposure to (L)-methionine may occur through inhalation and dermal contact with this compound at workplaces where (L)-methionine is produced or used. Monitoring and use data indicate that the general population may be exposed to (L)-methionine via ingestion of food or other consumer products containing (L)-methionine(SRC).
(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 19, 2010: https://www.cdc.gov/noes/

14.2.17 Body Burden

The average (L)-methionine content of human milk is reported as 19 mg/100 g(1).
(1) Drauz K et al; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). NY, NY: John Wiley & Sons; Amino Acids. Online Posting Date: Apr 15, 2007.

15 Associated Disorders and Diseases

Disease
Heart failure
References
Disease
Homocystinuria
References

PubMed: 14264314, 8745393

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

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
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
Tyrosinemia
References
Disease
Methylenetetrahydrofolate reductase deficiency
References

PubMed: 8456826

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

Disease
Hypermethioninemia
References
Disease
Glycine N-methyltransferase deficiency
References
PubMed: 27207470
Disease
Methionine adenosyltransferase deficiency
References
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
Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type
References
PubMed: 21559159
Disease
Citrullinemia type II, neonatal-onset
References
PubMed: 11281457
Disease
Cobalamin F disease (cblF)
References
PubMed: 21910240
Disease
Leukemia
References
Disease
Adenosine kinase deficiency
References
PubMed: 21963049
Disease
Irritable bowel syndrome
References
Disease
Diverticular disease
References
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
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 Drug-Drug Interactions

18.4 Drug-Food Interactions

Take with food.

18.5 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: ATC

21.6 KEGG: JP15

21.7 KEGG: Risk Category of Japanese OTC Drugs

21.8 WHO ATC Classification System

21.9 EPA Safer Choice

21.10 ChemIDplus

21.11 CAMEO Chemicals

21.12 ChEMBL Target Tree

21.13 UN GHS Classification

21.14 EPA CPDat Classification

21.15 NORMAN Suspect List Exchange Classification

21.16 CCSBase Classification

21.17 EPA DSSTox Classification

21.18 Consumer Product Information Database Classification

21.19 EPA TSCA and CDR Classification

21.20 LOTUS Tree

21.21 EPA Substance Registry Services Tree

21.22 MolGenie Organic Chemistry Ontology

22 Information Sources

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  13. Human Metabolome Database (HMDB)
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    http://www.hmdb.ca/citing
  14. New Zealand Environmental Protection Authority (EPA)
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  15. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
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  16. ChEBI
  17. E. coli Metabolome Database (ECMDB)
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    https://ecmdb.ca/citations
  18. LOTUS - the natural products occurrence database
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    https://lotus.nprod.net/
  19. NCI Thesaurus (NCIt)
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  20. Open Targets
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  21. Toxin and Toxin Target Database (T3DB)
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    http://www.t3db.ca/downloads
  22. CCSbase
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    https://ccsbase.net/
  23. NORMAN Suspect List Exchange
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    https://creativecommons.org/licenses/by/4.0/
    L-Methionine
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  24. ChEMBL
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  25. ClinicalTrials.gov
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  26. Comparative Toxicogenomics Database (CTD)
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  27. Drug Gene Interaction database (DGIdb)
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    http://www.dgidb.org/downloads
  28. Consumer Product Information Database (CPID)
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    https://www.whatsinproducts.com/contents/view/1/6
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  29. Cosmetic Ingredient Review (CIR)
  30. EPA Chemical and Products Database (CPDat)
  31. DailyMed
  32. Drug Induced Liver Injury Rank (DILIrank) Dataset
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  33. IUPAC Digitized pKa Dataset
  34. ECI Group, LCSB, University of Luxembourg
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    https://creativecommons.org/licenses/by/4.0/
    L-methionine
  35. Natural Product Activity and Species Source (NPASS)
  36. EPA Safer Choice
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  37. EU Food Improvement Agents
  38. EU Clinical Trials Register
  39. FDA Substances Added to Food
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  40. SpectraBase
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  43. NIST Mass Spectrometry Data Center
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    https://www.nist.gov/srd/public-law
  44. Japan Chemical Substance Dictionary (Nikkaji)
  45. KEGG
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    http://www.genome.jp/kegg-bin/get_htext?br08312.keg
  46. Kruve Lab, Ionization & Mass Spectrometry, Stockholm University
    methionine
  47. MarkerDB
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    https://markerdb.ca/
  48. Metabolomics Workbench
  49. National Drug Code (NDC) Directory
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  52. NIPH Clinical Trials Search of Japan
  53. NLM RxNorm Terminology
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  54. NMRShiftDB
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  57. RCSB Protein Data Bank (RCSB PDB)
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  60. Thieme Chemistry
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  61. WHO Anatomical Therapeutic Chemical (ATC) Classification
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  66. PubChem
  67. GHS Classification (UNECE)
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  69. MolGenie
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  70. PATENTSCOPE (WIPO)
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CONTENTS