2-Ketoglutaric acid
[CAS# 328-50-7]

Identification

• Classification: Chemical reagent >> Organic reagent >> Fatty acid
• Name: 2-Ketoglutaric acid
• Synonyms: 2-Oxoglutaric acid; 2-Oxopentanedioic acid ; alpha-Ketoglutaric acid
• Molecular Formula: C₅H₆O₅
• Molecular Weight: 146.10
• CAS Registry Number: 328-50-7
• EC Number: 206-330-3
• SMILES: C(CC(=O)O)C(=O)C(=O)O

Properties

• Density: 1.5±0.1 g/cm³, Calc.^*
• Melting point: 114-118 °C (Expl.)
• Index of Refraction: 1.494, Calc.^*
• Boiling Point: 345.6±25.0 °C (760 mmHg), Calc.^*, 323 °C (Expl.)
• Flash Point: 177.0±19.7 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Risk Statements: H315-H318-H335
• Safety Statements: P261-P264-P264+P265-P271-P273-P280-P302+P352-P304+P340-P305+P354+P338-P317-P319-P321-P332+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Serious eye damage	Eye Dam.	1	H318
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319
Skin corrosion	Skin Corr.	1B	H314
Specific target organ toxicity - single exposure	STOT SE	3	H336

Discovery and Applications

2-Ketoglutaric acid, also known as α-ketoglutaric acid, is a key intermediate in cellular metabolism, specifically in the Krebs cycle (citric acid cycle). It is an important compound in the biochemistry of living organisms, playing a central role in energy production and amino acid metabolism. This dicarboxylic acid is produced through the decarboxylation of glutamate and is involved in several essential metabolic processes. The discovery of 2-ketoglutaric acid dates back to the early 20th century, when scientists began elucidating the components of cellular respiration. Its significant biological functions were further explored with the development of biochemistry in the 1930s and 1940s, which laid the groundwork for understanding its role in metabolism.

2-Ketoglutaric acid is formed from glutamate by the enzyme glutamate dehydrogenase in a reversible reaction. It can also be produced through the action of other enzymes in the Krebs cycle, where it is involved in the synthesis of various amino acids such as proline, arginine, and glutamine. It plays a crucial role in the production of ATP (adenosine triphosphate), which is used as a source of energy for many cellular functions. As an intermediate in the Krebs cycle, it undergoes decarboxylation to form succinyl-CoA, a compound that ultimately helps drive the energy production process in cells. Additionally, 2-ketoglutaric acid serves as a precursor for the synthesis of neurotransmitters and other essential molecules.

The applications of 2-ketoglutaric acid extend beyond its role in metabolism. In the field of nutrition and health, it is utilized as a dietary supplement due to its potential benefits in promoting muscle recovery, enhancing exercise performance, and improving overall metabolic function. As a supplement, it is often used by athletes and bodybuilders to support muscle growth and reduce fatigue. The supplementation of 2-ketoglutaric acid is thought to improve the efficiency of energy production within cells, leading to enhanced performance during physical activity.

In the medical and pharmaceutical industries, 2-ketoglutaric acid has been investigated for its potential therapeutic effects. It is considered a valuable compound in the treatment of certain diseases related to metabolism and aging. Research has shown that it may help in improving mitochondrial function, which is crucial for maintaining cellular health and function over time. Its use in clinical settings includes its potential to treat conditions such as chronic fatigue syndrome, neurodegenerative diseases, and other age-related conditions.

In addition to its nutritional and pharmaceutical uses, 2-ketoglutaric acid is also studied for its potential applications in agriculture. Its role in amino acid metabolism makes it useful in promoting plant growth and improving the efficiency of nitrogen utilization in plants. As plants require amino acids for growth and development, the use of 2-ketoglutaric acid in agricultural practices can enhance plant health, increase crop yields, and improve overall agricultural productivity.

Further research into 2-ketoglutaric acid continues to explore its broader applications, particularly in metabolic disorders and its use in precision medicine. As a naturally occurring compound in the human body and other organisms, its safety profile is well understood, and its potential for therapeutic use in various medical and agricultural applications continues to be a promising area of study.

References

1979. Assay of citric acid cycle intermediates and related compounds--update with tissue metabolite levels and intracellular distribution. Methods in enzymology, 55.
DOI: 10.1016/0076-6879(79)55025-3

1969. Mechanism of non-enzymic transamination reaction between histidine and alpha-oxoglutaric acid. The Biochemical journal, 112(5).
DOI: 10.1042/bj1120691

2024. Integrated physiological, metabolome, and transcriptome analysis of the hepatopancreas in Penaeus vannamei under ammonia stress. Aquaculture International, Not applicable.
DOI: 10.1007/s10499-024-01599-w