Methionine, L-Methionine, DL-Methionine, Metilanin, 63-68-3, 59-51-8

METHIONINE

Methionine / L-Methionine / DL-Methionine / Metilanin / 2-Amino-4-(methylthio)butanoic Acid
CAS Numbers: 63-68-3 (L-Methionine); 59-51-8 (DL-Methionine)
EC Numbers: 200-562-9 (L); 200-432-1 (DL)

1. PRODUCT IDENTIFICATION AND CHEMICAL IDENTITY

Methionine is one of the nine essential amino acids that the human body cannot synthesize on its own and must obtain through diet or supplementation. It is a sulfur-containing amino acid that plays a critical role in protein synthesis and various metabolic processes. Methionine exists in two forms: L-Methionine (the biologically active form) and DL-Methionine (a racemic mixture of D- and L- isomers). L-Methionine is the naturally occurring form found in proteins and is the biologically active isomer. DL-Methionine is a synthetic mixture containing both D- and L-isomers, commonly used in animal feed and some supplements. L-Methionine is a white crystalline powder or colorless plates with a sulfurous taste. It is an essential amino acid that serves as a precursor to other important sulfur-containing compounds including cysteine, taurine, S-adenosylmethionine (SAM-e), and glutathione. Methionine is also involved in the synthesis of creatine, carnitine, and various phospholipids. It is naturally found in protein-rich foods such as meat, fish, eggs, dairy products, and legumes. Methionine is produced synthetically through chemical synthesis or fermentation and is widely used in dietary supplements, animal feed, pharmaceuticals, and the food industry.

2. PHYSICAL AND CHEMICAL PROPERTIES

Methionine is a white crystalline powder or colorless plates with a sulfurous taste. L-Methionine has a melting point of 280-282°C (decomposes), while DL-Methionine melts at 281°C. The boiling point is approximately 181°C (decomposes). Water solubility at 25°C is approximately 56.6 g/L for L-Methionine and 53.7 g/L for DL-Methionine. Both forms are soluble in dilute ethanol. The specific optical rotation is +23.0 to +24.5° for L-Methionine (c=1, H₂O), while DL-Methionine as a racemic mixture has an optical rotation of 0°. The pKa values are 2.28 (carboxyl group) and 9.21 (amino group), with an isoelectric point of 5.74. The nitrogen content is approximately 9.4% by weight, and the sulfur content is approximately 21.5% by weight. Typical moisture content is ≤ 0.5%, and residue on ignition is ≤ 0.3%. Heavy metals are typically ≤ 10 ppm (as Pb). Chloride and sulfate content are each ≤ 0.05%.

3. CHEMICAL PROPERTIES AND REACTIONS

Methionine is a sulfur-containing amino acid with a thioether group (-S-CH₃) in its side chain. This unique structure gives methionine its distinctive chemical properties and reactivity.

Acid-Base Properties:

Methionine has both carboxyl (COOH) and amino (NH₂) groups. In aqueous solution, it has the following ionization equilibria:

• pKa₁ (COOH): 2.28 (carboxyl group deprotonation)

• pKa₂ (α-NH₂): 9.21 (amino group deprotonation)

• Isoelectric Point: 5.74

S-Adenosylmethionine (SAM-e) Formation:

Methionine is converted to S-adenosylmethionine (SAM-e) through reaction with ATP by the enzyme methionine adenosyltransferase:

Methionine + ATP → SAM-e + PPi + Pi (S-adenosylmethionine formation)

SAM-e is a critical methyl donor involved in numerous methylation reactions in the body.

Transsulfuration Pathway:

Methionine is converted to cysteine through the transsulfuration pathway:

Methionine → SAM-e → Homocysteine → Cysteine

Decarboxylation:

Methionine can be decarboxylated to form various amines.

Oxidation:

Methionine can be oxidized to methionine sulfoxide and methionine sulfone. The sulfur atom in the thioether group is susceptible to oxidation.

Reaction with Halogens:

Methionine reacts with halogens (chlorine, bromine, iodine) to form sulfonium salts.

Methylation Reactions:

Methionine, through SAM-e, is a key methyl donor in numerous biological methylation reactions, including the synthesis of creatine, carnitine, and various neurotransmitters.

Thermal Decomposition:

At temperatures above 280°C, methionine decomposes to produce volatile compounds including sulfur-containing gases (methanethiol, hydrogen sulfide, sulfur dioxide), ammonia, and various nitrogen-containing compounds.

4. DIFFERENCES BETWEEN L-METHIONINE AND DL-METHIONINE

L-Methionine:

L-Methionine is the naturally occurring form of methionine found in proteins. It is the biologically active form that is directly incorporated into proteins during protein synthesis. It has high bioavailability and is readily utilized by the body. L-Methionine is primarily used in human nutrition, dietary supplements, and pharmaceutical applications. It is produced through fermentation using microorganisms such as Corynebacterium glutamicum or Escherichia coli.

DL-Methionine:

DL-Methionine is a racemic mixture containing equal amounts of D- and L-isomers (50% D, 50% L). The D-isomer is not biologically active and must be converted to the L-form in the body through enzymatic racemization. This conversion is limited and inefficient in humans, making DL-methionine less bioavailable than L-methionine. DL-Methionine is primarily used in animal feed because animals (especially poultry and livestock) can effectively convert the D-isomer to the L-form. It is produced through chemical synthesis and is more economical than L-methionine.

5. PHYSIOLOGICAL FUNCTIONS AND HEALTH BENEFITS

Methionine is an essential amino acid that plays numerous critical roles in the body. It is involved in protein synthesis, methylation reactions, sulfur metabolism, and the production of other important biomolecules.

5.1. Protein Synthesis

Methionine is one of the nine essential amino acids required for protein synthesis. It is incorporated into proteins during translation and is necessary for the formation of all proteins in the body. Adequate methionine intake is critical for growth, development, tissue repair, and maintenance of muscle mass.

5.2. Methyl Donor (Through SAM-e)

Methionine is converted to S-adenosylmethionine (SAM-e), which is a critical methyl donor involved in numerous methylation reactions. SAM-e contributes to the synthesis of creatine, carnitine, and various neurotransmitters. It is also involved in DNA methylation, which regulates gene expression. SAM-e is used as a dietary supplement for depression, osteoarthritis, and liver health.

5.3. Sulfur Metabolism and Antioxidant Function

Methionine is a precursor to cysteine, which is used to synthesize glutathione—one of the body's most important antioxidants. Glutathione protects cells from oxidative stress, supports immune function, and aids in detoxification. Methionine is also a precursor to taurine, an amino acid important for heart and eye health.

5.4. Liver Health and Detoxification

Methionine supports liver function and protects against liver damage. It is used in the treatment of acetaminophen (paracetamol) overdose to prevent liver damage by replenishing glutathione levels. Methionine also supports general detoxification processes in the liver.

5.5. Other Health Benefits

6. APPLICATIONS AND INDUSTRIAL USES

Methionine has a wide range of applications in human nutrition, animal nutrition, pharmaceuticals, the food industry, and cosmetics.

6.1. Human Nutrition and Dietary Supplements

L-Methionine is widely used as a dietary supplement in human nutrition. It is used in amino acid blends, protein supplements, and sports nutrition products. L-Methionine is also used as a precursor to SAM-e, which is available as a supplement for depression, osteoarthritis, and liver health. It is particularly important for individuals on plant-based diets, as plant proteins are often low in methionine.

6.2. Animal Nutrition and Feed Additives

DL-Methionine is widely used as an essential amino acid supplement in animal nutrition. It is often the first limiting amino acid in poultry and livestock feeds (especially corn and soybean-based feeds). Supplementation improves growth, feed conversion efficiency, egg production, and milk production. DL-Methionine is more economical than L-Methionine for animal feed applications because animals can effectively convert the D-isomer to the L-form.

6.3. Pharmaceutical Industry

L-Methionine is used in pharmaceutical applications for the treatment of acetaminophen overdose, liver diseases, and urinary tract conditions. It is also used as an ingredient in various drug formulations and in amino acid infusion solutions for parenteral nutrition. SAM-e is used as a pharmaceutical ingredient for depression, osteoarthritis, and liver health.

6.4. Food Industry

Methionine is used in the food industry as a nutrient supplement and antioxidant. It is added to fortified foods, sports nutrition products, infant formula, and baked goods. It is used as a flour treatment agent and dough conditioner in baked goods.

6.5. Cosmetics and Personal Care

L-Methionine is used in cosmetics and personal care products as an antioxidant, skin-conditioning agent, and hair conditioner. It is also used as an antistatic agent in hair and skin care products.

7. DOSAGE AND ADMINISTRATION

8. POTENTIAL SIDE EFFECTS AND WARNINGS

9. DRUG INTERACTIONS

10. NATURAL FOOD SOURCES OF METHIONINE

11. SAFETY AND TOXICOLOGY

12. FIRST AID MEASURES

13. SAFETY INFORMATION (GHS CLASSIFICATION)

Signal Word: WARNING

Hazard Statements (H-Codes):

Precautionary Statements (P-Codes):

14. FIREFIGHTING MEASURES

15. ACCIDENTAL RELEASE MEASURES

16. STORAGE AND HANDLING

Methionine should be stored below 25°C in cool, dry, well-ventilated areas, protected from light. It is slightly hygroscopic and should be protected from moisture. Containers should be kept tightly closed to prevent moisture absorption and contamination. It is incompatible with strong oxidizing agents, strong acids, and strong bases. Shelf life under proper storage conditions is typically 24-36 months.

Handling Notes:

• Avoid dust generation (use enclosed systems, local exhaust ventilation)

• Avoid contact with skin and eyes (use protective gloves and goggles)

• Avoid breathing dust (use dust mask or respirator)

• Keep away from ignition sources

• Do not allow material to become wet

17. TRANSPORT INFORMATION

Methionine is not classified as a dangerous good for transport. It is shipped in 25 kg bags, drums, or FIBCs. During transport, protect from moisture, impact, and excessive heat.

18. REGULATORY INFORMATION

Regulatory Status:

19. OTHER NAMES AND DATABASE IDENTIFIERS

Database Identifiers:

20. SUMMARY AND CRITICAL WARNINGS

SUMMARY:

Methionine (C₅H₁₁NO₂S) is one of the nine essential amino acids that the human body cannot synthesize and must obtain through diet or supplementation. It is a sulfur-containing amino acid that exists in two forms: L-Methionine (the biologically active form, CAS 63-68-3) and DL-Methionine (a racemic mixture, CAS 59-51-8). L-Methionine is a white crystalline powder or colorless plates with a sulfurous taste. The molecular weight is 149.21 g/mol, melting point is 280-282°C (decomposes), and water solubility at 25°C is approximately 56.6 g/L. It is produced through fermentation or chemical synthesis. Methionine plays critical roles in protein synthesis, methylation reactions (as a precursor to SAM-e), sulfur metabolism, and antioxidant function (as a precursor to glutathione and cysteine). It is widely used in dietary supplements, animal feed, pharmaceuticals, the food industry, and cosmetics. L-Methionine is used in human nutrition and pharmaceutical applications, while DL-Methionine is primarily used in animal feed due to its lower cost. The recommended supplement dose is typically 500-1,500 mg per day. It is considered GRAS (Generally Recognized as Safe) by the FDA, but high doses may cause gastrointestinal distress and hyperhomocysteinemia. It is stored below 25°C in cool, dry, well-ventilated areas, protected from moisture and light. Packaging: 25 kg bags, drums, or FIBCs.

Key Properties:

Major Application Areas:

Key Safety Points:

• LOW TOXICITY: GRAS (Generally Recognized as Safe) by FDA

• SLIGHTLY HYGROSCOPIC: Protect from moisture; store in tightly closed containers

• MILD IRRITANT: May cause mild skin and eye irritation

• STORAGE: Store below 25°C in cool, dry, well-ventilated area, protected from light

• PPE REQUIRED: Dust mask, safety goggles, protective gloves (for handling powder)

• SIDE EFFECTS: May cause gastrointestinal distress at high doses; risk of hyperhomocysteinemia

• DRUG INTERACTIONS: May interact with levodopa (L-Dopa) and other Parkinson's medications

• CONTRAINDICATIONS: Homocysteinuria, cystinuria, sulfite sensitivity, severe liver disease

CRITICAL WARNINGS:

Essential Sulfur-Containing Amino Acid: Methionine is one of the nine essential amino acids and is the primary source of sulfur in the body. It is critical for protein synthesis, methylation reactions, and the production of other important sulfur-containing compounds (cysteine, taurine, glutathione, SAM-e). Deficiency can lead to poor growth, impaired immune function, and various metabolic disorders.

L-Methionine vs. DL-Methionine: L-Methionine is the biologically active form found in proteins and is directly used in protein synthesis. DL-Methionine is a synthetic racemic mixture containing both D- and L-isomers. The D-isomer must be converted to the L-form in the body, making DL-Methionine less bioavailable in humans. DL-Methionine is primarily used in animal feed because animals can effectively convert the D-isomer to the L-form. For human nutrition and pharmaceutical applications, L-Methionine is the preferred form.

SAM-e and Methylation: Methionine is converted to S-adenosylmethionine (SAM-e), which is a critical methyl donor involved in numerous methylation reactions. SAM-e contributes to the synthesis of creatine, carnitine, and various neurotransmitters. It is also involved in DNA methylation, which regulates gene expression. SAM-e is used as a dietary supplement for depression, osteoarthritis, and liver health. Adequate intake of vitamin B6, B12, and folate is required for optimal SAM-e production.

Antioxidant Function: Methionine is a precursor to cysteine, which is used to synthesize glutathione—one of the body's most important antioxidants. Glutathione protects cells from oxidative stress, supports immune function, and aids in detoxification. Methionine also provides sulfur for the synthesis of other sulfur-containing compounds with antioxidant properties.

Liver Health and Detoxification: Methionine supports liver function and protects against liver damage. It is used in the treatment of acetaminophen (paracetamol) overdose to prevent liver damage by replenishing glutathione levels. Methionine also supports general detoxification processes in the liver.

Hyperhomocysteinemia Risk: High doses of methionine can lead to elevated homocysteine levels (hyperhomocysteinemia), which is a risk factor for cardiovascular disease. Individuals with pre-existing conditions or those taking high doses should be monitored by a healthcare professional. Adequate intake of vitamin B6, B12, and folate can help maintain normal homocysteine levels.

Drug Interactions: Methionine may interact with levodopa (L-Dopa), a medication used for Parkinson's disease, by interfering with its absorption. It is recommended to administer L-Dopa 1-2 hours before or after taking methionine.

Natural Food Sources: Methionine is naturally found in protein-rich foods including meat, poultry, fish, eggs, dairy products, soybeans, sesame seeds, Brazil nuts, and sunflower seeds. Individuals on plant-based diets may have a higher risk of methionine deficiency and may benefit from supplementation.

Pregnancy and Lactation: Methionine is generally considered safe during pregnancy and lactation at recommended doses. However, as with all supplements, it is recommended to consult a healthcare professional before use.

Important Disclaimer: This Technical Data Sheet (TDS) is for informational purposes only. The information provided is based on available data and is believed to be accurate. However, the user is solely responsible for determining the suitability of the product for their specific application and for complying with all applicable regulations and safety requirements. For complete safety, handling, storage, and regulatory compliance information, always refer to the official Safety Data Sheet (SDS/MSDS) provided by the manufacturer/supplier. Users are responsible for testing the product in their own processes and applications. All local, national, and international regulations must be followed when working with methionine. This is NOT a substitute for professional medical advice. Consult a healthcare professional before use, especially if taking medications, pregnant, or nursing.