In addition to its physiological roles, 2-ketoglutarate (also known as alpha-ketoglutarate) also protects against lipid peroxidation, reduces ammonia levels produced in the lungs, and provides neuroprotection against cyanide poisoning [1]. The synthesis of nucleotides and amino acids requires 2-oxoglutarate as a precursor [2].

[1]. Huergo LF, et al. The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite. Microbiol Mol Biol Rev. 2015 Dec;79(4):419-35.
[2]. Gou L, et al. The effect of alpha-ketoglutaric acid on tyrosinase activity and conformation: Kinetics and molecular dynamics simulation study. Int J Biol Macromol. 2017 Dec;105(Pt 3):1654-1662.

2-oxoglutaric acid is an oxo dicarboxylic acid that consists of glutaric acid bearing an oxo substituent at position 2. It is an intermediate metabolite in Krebs cycle. It has a role as a fundamental metabolite. It is functionally related to a glutaric acid. It is a conjugate acid of a 2-oxoglutarate(1-).
Oxogluric acid (α-Ketoglutarate) is not approved for any indication in the world but is an investigational drug in the United States. In the United States a phase I clinical trial is investigating whether oxogluric acid precursors found in nutritional supplements can benefit patients with the metabolic disorder propionic acidemia. Oxogluric acid is sold as a dietary supplement to athletes to improve their performance by helping to remove excess ammonia, but it is not officially approved for this indication and only experimental studies have shown a reduction in ammonia by oxogluric acid in hemodialysis patients. Physiologically, oxogluric acid acts in the Krebs cycle as an intermediate, is involved in transamination reactions during the metabolism of amino acids, forms glutamic acid by combining with ammonia, and reduces nitrogen by combining with it as well. Several experimental studies have also shown that administration of oxogluric acid helped attenuate the decreased synthesis of muscle protein that is often seen post-surgery.
Oxoglutaric acid is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
alpha-Ketoglutarate is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
2-Oxoglutaric acid has been reported in Humulus lupulus, Drosophila melanogaster, and other organisms with data available.
A family of compounds containing an oxo group with the general structure of 1,5-pentanedioic acid. (From Lehninger, Principles of Biochemistry, 1982, p442)

---

Drug Indication
α-α-Ketoglutarate is not approved for any indication in the world but is an investigational drug in the United States. The potential indications for α-Ketoglutarate are in patients with the metabolic disorder propionic acidemia and in trauma patients with muscle loss.

---

Mechanism of Action
The exact mechanisms of action for α-Ketoglutarate have not yet been elucidated. Some of α-Ketoglutarate’s actions include acting in the Krebs cycle as an intermediate, transamination reactions during the metabolism of amino acids, forming glutamic acid by combining with ammonia, and reducing nitrogen by combining with it as well. Concerning α-Ketoglutarate’s actions with ammonia, it is proposed that α-Ketoglutarate can help patients with propionic academia who have high levels of ammonia and low levels of glutamine/glutamate in their blood. Because endogenous glutamate/glutamine is produced from α-Ketoglutarate, propionic acidemia patients have impaired production of α-Ketoglutarate and supplementation of α-Ketoglutarate should improve the condition of these patients. Several other experimental studies have also shown that administration of α-Ketoglutarate in parenteral nutrition given to post-operative patients helped attenuate the decreased synthesis of muscle protein that is often seen after a surgery. This decreased muscle synthesis is speculated to be due to too low α-Ketoglutarate levels.

---

Pharmacodynamics
All of the physiological roles of alpha-ketoglutarate have not been determined. What is known is that alpha-keotglutarate is involved in the Krebs cycle, transamination reactions, and promotes muscle synthesis.

C5H6O5

146.09814

146.021

328-50-7

2-Ketoglutaric acid Sodium;22202-68-2;2-Ketoglutaric acid-13C5;161096-83-9;2-Ketoglutaric acid-13C;108395-15-9;Calcium 2-oxoglutarate;71686-01-6;2-Ketoglutaric acid-d4;1381759-60-9;2-Ketoglutaric acid-d6;1173021-86-7

51

Typically exists as solid at room temperature

1.5±0.1 g/cm3

345.6±25.0 °C at 760 mmHg

113-115 °C

177.0±19.7 °C

0.0±1.6 mmHg at 25°C

1.494

-1.43

2

5

4

10

171

0

OC(=O)CCC(=O)C(O)=O

KPGXRSRHYNQIFN-UHFFFAOYSA-N

InChI=1S/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10)

2-oxopentanedioic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~1711.16 mM)
H2O : ~50 mg/mL (~342.23 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (14.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (14.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (14.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 100 mg/mL (684.46 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

---

 (Please use freshly prepared in vivo formulations for optimal results.)