Isoleucine, L-Isoleucine, 2-Amino-3-methylvaleric Acid, BCAA, 73-32-5

L-ISOLEUCINE

L-Isoleucine / Isoleucine / (2S,3S)-2-Amino-3-methylpentanoic acid / BCAA
CAS Number: 73-32-5
EC Number: 200-798-2

1. PRODUCT IDENTIFICATION AND CHEMICAL IDENTITY

L-Isoleucine is an essential, branched-chain amino acid (BCAA) belonging to the same family as L-leucine and L-valine. It is one of the nine essential amino acids that cannot be synthesized by the human body and must be obtained through diet or supplementation . L-Isoleucine has two chiral centers and exerts its physiological activity solely through its L-isomer . It plays a critical role in muscle metabolism, energy production, immune function, and glucose homeostasis. L-Isoleucine appears as crystalline leaflets or a white, crystalline powder, is odorless, and has a bitter taste . It is soluble in water (approximately 40 g/L at 25°C), slightly soluble in hot alcohol, soluble in diluted mineral acids and alkaline solutions, and insoluble in ether . L-Isoleucine is widely used in sports nutrition, dietary supplements, medical applications, the food industry, and animal feed .

2. PHYSICAL AND CHEMICAL PROPERTIES

L-Isoleucine is a white, crystalline powder with a bitter taste. It has a melting point of 279-284°C, at which it decomposes. It sublimes between 168-170°C . Its water solubility at 25°C is approximately 40 g/L . It is slightly soluble in hot alcohol but soluble in diluted mineral acids and alkaline solutions . The pH of a 1:100 aqueous solution is 5.5-7.0 . The specific optical rotation is +38.9 to +41.8° (c=4, 6N HCl) . The pKa values are 2.36 and 9.68 .

3. CHEMICAL PROPERTIES AND REACTIONS

L-Isoleucine is a branched-chain amino acid (BCAA) with a hydrophobic, aliphatic side chain. Its chemical behavior is determined by its amino acid functional groups and the branched side chain.

Acid-Base Properties:

L-Isoleucine has both carboxyl (COOH) and amino (NH₂) groups. pKa values: 2.36 (pK1) and 9.68 (pK2) .

Esterification:

L-Isoleucine can be esterified with alcohols to form isoleucine esters, which are used as pharmaceutical intermediates.

Acylation:

The amino group of L-isoleucine can be acylated to form N-acyl derivatives for peptide synthesis and pharmaceutical applications.

Transamination:

L-Isoleucine participates in transamination reactions, transferring its amino group to α-ketoglutarate to form glutamate and α-keto-β-methylvalerate.

Thermal Decomposition:

Above its melting point, L-isoleucine decomposes, producing ammonia, carbon dioxide, and various nitrogen-containing compounds.

4. PRODUCTION METHODS

L-Isoleucine is produced industrially primarily through microbial fermentation using metabolically engineered microorganisms.

Detailed Production Process (Fermentation Method - Most Common):

Current industrial production of L-isoleucine primarily relies on microbial fermentation . Corynebacterium glutamicum and Escherichia coli are the primary host strains used for industrial production .

Key Metabolic Engineering Strategies:

1. Feedback Inhibition Relief: Removing feedback inhibition of key enzymes such as aspartokinase, threonine dehydratase (TD), and acetohydroxy acid synthase (AHAS) is critical .

2. Pathway Optimization: Overexpression of key genes including lysC^A279T, *ilvA^G418A/T1147G*, and *ilvBN^A139T/T140A* enhances the L-isoleucine synthetic pathway .

3. Cofactor Supply Enhancement: Each L-isoleucine molecule requires five NADPH molecules for biosynthesis; enhancing NADPH availability improves production .

4. Efflux System Promotion: Overexpression of brnFE promotes L-isoleucine efflux, increasing production .

Recent Production Achievements:

• An engineered E. coli strain (ISO-12) achieved 51.5 g/L L-isoleucine in a 5L fermenter .

• A whole-cell biocatalysis system achieved 98.4% conversion of L-threonine to L-isoleucine, producing 40.1 g/L within 36 hours .

• A metabolically engineered C. glutamicum strain produced 21.3 g/L L-isoleucine after 48 hours .

5. PHYSIOLOGICAL FUNCTIONS AND HEALTH BENEFITS

L-Isoleucine is an essential branched-chain amino acid that plays numerous critical roles in the body. It regulates glucose homeostasis, muscle protein synthesis, liver metabolism, and immune function .

5.1. Energy Production and Muscle Metabolism

Branched-chain amino acids, including L-isoleucine, are primarily metabolized in muscle tissue rather than the liver. L-Isoleucine acts as a pivotal regulator of muscle protein synthesis by activating the mammalian target of rapamycin (mTOR) signaling pathway, facilitating post-exercise muscle fiber repair . It is also a key component of parenteral nutrition formulations .

5.2. Immune Function

L-Isoleucine plays a role in immune function and may enhance resistance to infections.

5.3. Other Health Benefits

6. APPLICATIONS AND INDUSTRIAL USES

L-Isoleucine has a wide range of applications in sports nutrition, dietary supplements, medical applications, the food industry, animal feed, and cosmetics .

6.1. Sports Nutrition and Dietary Supplements

L-Isoleucine is a key component of BCAA blends and sports nutrition products due to its role in muscle protein synthesis and energy metabolism .

6.2. Food Industry

L-Isoleucine is listed as a flavoring agent and nutrient supplement by the FDA .

6.3. Pharmaceutical Applications

L-Isoleucine is a key component of parenteral nutrition formulations in biopharmaceuticals .

6.4. Animal Nutrition

The FDA has reviewed L-isoleucine fermentation product for use as a source of L-isoleucine in poultry and swine feed .

6.5. Cosmetics and Personal Care

7. DOSAGE AND ADMINISTRATION

8. POTENTIAL SIDE EFFECTS AND WARNINGS

9. NATURAL FOOD SOURCES OF L-ISOLEUCINE

10. SAFETY AND TOXICOLOGY

11. FIRST AID MEASURES

12. SAFETY INFORMATION (GHS CLASSIFICATION)

L-Isoleucine is not classified as a hazardous substance under GHS.

Signal Word: WARNING

Hazard Statements (H-Codes):

13. STORAGE AND HANDLING

L-Isoleucine should be stored at 2-30°C in cool, dry, well-ventilated areas . It is slightly hygroscopic and should be protected from moisture. Containers should be kept tightly closed to prevent moisture absorption and contamination.

14. TRANSPORT INFORMATION

L-Isoleucine is not classified as a dangerous good for transport. It is shipped in 25 kg bags, drums, or FIBCs.

15. REGULATORY INFORMATION

Regulatory Status:

16. OTHER NAMES AND SYNONYMS

17. APPLICATION SUMMARY TABLE

18. SUMMARY AND CRITICAL WARNINGS

SUMMARY:

L-Isoleucine (C₆H₁₃NO₂, CAS 73-32-5) is an essential branched-chain amino acid (BCAA) belonging to the same family as L-leucine and L-valine. It appears as crystalline leaflets or a white, crystalline powder, is odorless, and has a bitter taste . The molecular weight is 131.17 g/mol, melting point is 279-284°C (decomposes), and water solubility at 25°C is approximately 40 g/L . It is produced primarily through microbial fermentation using Corynebacterium glutamicum or Escherichia coli . L-Isoleucine plays critical roles in energy production, muscle metabolism, immune function, glucose homeostasis, and liver metabolism . It is widely used in sports nutrition (BCAA supplements, energy drinks, protein powders), dietary supplements, medical applications (metabolic disorders, muscle wasting, parenteral nutrition), the food industry (functional foods, flavor enhancer), and animal feed . It is considered GRAS (Generally Recognized as Safe) by the FDA . It is stored at 2-30°C in cool, dry, well-ventilated areas . Packaging: 25 kg bags, drums, or FIBCs.

Key Properties:

Major Application Areas:

Key Safety Points:

• LOW TOXICITY: GRAS by FDA

• SLIGHTLY HYGROSCOPIC: Protect from moisture

• MILD IRRITANT: May cause mild skin and eye irritation

• STORAGE: Store at 2-30°C in cool, dry, well-ventilated area 

• CONTRAINDICATIONS: Maple syrup urine disease (MSUD)

CRITICAL WARNINGS:

Essential BCAA: L-Isoleucine is one of the three branched-chain amino acids (BCAAs) and cannot be synthesized by the body. BCAAs are unique because they are metabolized primarily in muscle tissue rather than the liver, making them critical for muscle protein synthesis and energy production during exercise .

Energy Metabolism: L-Isoleucine serves as an important energy source in muscle tissue, particularly during prolonged exercise. As a branched-chain amino acid, it is oxidized in skeletal muscle rather than the liver and can be used directly as fuel during exercise .

Muscle Protein Synthesis: Like other BCAAs, L-isoleucine stimulates muscle protein synthesis, supporting muscle growth and repair. Along with leucine, it activates protein synthesis through the mTOR pathway .

Maple Syrup Urine Disease (MSUD): L-Isoleucine is strictly contraindicated in patients with maple syrup urine disease (MSUD), a rare genetic disorder characterized by the inability to metabolize branched-chain amino acids.

Market and Applications: The global L-isoleucine market is growing rapidly due to increasing interest in sports nutrition and the prevalence of chronic health conditions. It is expected to grow from USD 42 million in 2020 to USD 55 million by 2026. Key applications include food (flavor enhancer), pharmaceuticals (parenteral nutrition), and cosmetics (anti-allergic skincare products) .

Important Disclaimer: This Technical Data Sheet (TDS) is for informational purposes only. The information provided is based on available data. 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.