2-Ketoglutaric Acid (also known as α-Ketoglutaric Acid) is an important organic acid with broad applications in biological metabolism, industrial production, and the pharmaceutical field. Below is a detailed introduction from the perspectives of its properties, functional characteristics, and applications:

I. Basic Properties

1. Chemical Structure and Nomenclature

Chemical name: 2-Oxoglutaric acid

Molecular formula: C₅H₆O₅

Molecular weight: 146.10

Belongs to the α-keto acid family (a ketone group is attached to the alpha carbon).

Structural formula: HOOC-(CH₂)₂-CO-COOH

2. Physical Properties

Appearance: White to pale yellow crystalline powder with a slightly acidic odor.

Solubility: Highly soluble in water (\~50g/100mL at 25°C), soluble in methanol and ethanol, slightly soluble in ether and acetone, insoluble in non-polar solvents like benzene and chloroform.

Melting point: Approx. 113–115°C; decomposes above 150°C releasing CO₂.

Stability: Stable in dry conditions; aqueous solutions are prone to oxidation, especially under light or high temperature—thus require protection from light and sealing.

Acidity: A dibasic acid with two carboxyl groups, pKa₁ ≈ 2.5 and pKa₂ ≈ 4.3; aqueous solution is acidic (pH \~2–3).

3. Chemical Properties

Acidic character: Can react with bases and metal oxides to form salts (e.g., sodium or calcium 2-ketoglutarate, which have better solubility).

Keto group reactivity: The keto group can undergo reduction (to 2-hydroxyglutaric acid) or condensation reactions (e.g., Schiff base formation with amines).

Oxidation/degradation: Can be further oxidized to succinic acid via enzymes or strong oxidants—serving as a key intermediate in the tricarboxylic acid (TCA) cycle.

II. Functional Characteristics

1. Central Role in Metabolism

A critical intermediate in the TCA cycle, connecting carbohydrate, fat, and amino acid metabolism.

Converts to glutamate via transamination (important for protein synthesis) or further degrades to CO₂ and water to provide cellular energy.

Acts as a metabolic hub, and its concentration directly influences energy metabolism and biosynthesis efficiency—key to maintaining metabolic balance.

2. Antioxidant and Cytoprotective Effects

Scavenges free radicals (e.g., hydroxyl radicals), reducing oxidative stress and protecting sensitive cells such as cardiomyocytes and neurons.

Participates in the synthesis of glutathione (a major cellular antioxidant), indirectly boosting the body’s antioxidative defense.

3. Promotion of Nitrogen Metabolism and Protein Synthesis

As a substrate of glutamate dehydrogenase, it facilitates the detoxification of ammonia into glutamate, lowering blood ammonia levels and reducing liver burden—especially beneficial during liver impairment.

Serves as a precursor for amino acid synthesis in muscle tissue, helping preserve muscle mass and minimize catabolism (e.g., during exercise or fasting).

4. Biocompatibility and Safety

Naturally occurring metabolite in the body; exogenous supplementation shows high biocompatibility with low risk of immunogenic or toxic reactions (at standard doses).

Clearly defined metabolic pathway—ultimately decomposed into CO₂ and water with no cumulative toxicity. Suitable for long-term or high-dose use under medical supervision.

III. Applications

1. Medical and Health Field

Liver disease support: Aids in ammonia detoxification (conversion to glutamate), lowering blood ammonia and alleviating symptoms in conditions like hepatic encephalopathy and cirrhosis.

Neuroprotection: As a metabolic regulator, it improves brain energy metabolism; used in research and supportive therapy for Alzheimer’s and Parkinson’s disease (clinical studies suggest it may slow cognitive decline).

Sports nutrition and muscle protection:

Used as a sports supplement to reduce muscle breakdown post-exercise (inhibits creatine kinase elevation), speeding recovery—especially valuable for high-intensity athletes.

Supports treatment of muscle atrophy by promoting protein synthesis and slowing muscle loss.

Oxidative stress-related diseases:

Aids in managing diabetic complications (e.g., nephropathy, neuropathy) by mitigating oxidative damage, improving vascular and neural function.

2. Food and Feed Industry

Food additive: Acts as a mild acidulant and nutritional enhancer in functional beverages and sports foods, replenishing metabolic intermediates and improving taste (less sour than citric acid).

Feed additive:

Enhances energy metabolism in livestock and poultry, promoting growth (e.g., improves weight gain and feed conversion in broilers and piglets).

Strengthens stress resistance in aquatic animals (e.g., fish, shrimp) under harsh conditions (heat, poor water quality), reducing mortality rates.

3. Biochemical and Research Use

Biosynthesis precursor: Used in fermentation processes for the production of amino acids like glutamate and lysine (boosting yield as a key intermediate).

Research reagent:

Added to cell culture media to maintain metabolic balance.

Substrate in enzymatic assays (e.g., glutamate dehydrogenase activity), supporting metabolic pathway studies.

4. Cosmetics Field

Due to its antioxidant properties, it is added to anti-aging skincare products to reduce free radical damage, delay wrinkle formation, and improve skin elasticity.

IV. Precautions

High doses (beyond physiological needs) may cause gastrointestinal discomfort (e.g., nausea, diarrhea); follow medical guidance for supplementation.

Use caution when combined with certain medications (e.g., antiepileptics, metabolic inhibitors) due to possible interference with metabolic balance.

As a food or feed additive, its maximum usage must comply with relevant national regulations (e.g., EU EFSA, China GB standards).

With its central role in metabolism, multiple physiological activities, and excellent safety profile, 2-Ketoglutaric Acid offers significant application value in medicine, food, and agriculture—especially in treating metabolic diseases and enhancing nutritional support.