2-Oxoglutaric

Optimal result: 0 – 33 mmol/mol creatinine

Elevated levels of 2-Oxoglutaric suggest dietary vitamin deficiencies or supplementation with 2-ketoglutaric acid. Coenzyme A (derived from pantothenic acid), flavin adenine dinucleotide (FAD) (derived from riboflavin), and thiamine are required for conversion of 2-oxoglutaric acid to succinyl-CoA.

Other potential factors:

  • Arsenic exposure

  • Pharmaceutical lithium

  • B1 or B2 deficiency

  • glutamine supplementation

  • Urea cycle disorders and/or hyperammonemia

  • Zinc excess

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HIGH LEVELS of alpha-ketoglutarate may occur when there are nutritional enzyme inhibitions of the breakdown pathways, inherited low-activity enzymes are present, if there are high levels of precursors (isocitrate), or if there are higher levels of its downstream products (succinate). Levels may also increase with supplementation. The most important enzyme activity in the CAC is the conversion of alpha-ketoglutarate into succinyl-CoA, which feeds into the electron transport chain (ETC) to produce ATP energy. This is one of two rate-determining irreversible steps on the CAC. Accumulation of alpha-ketoglutarate may be associated with liver problems; acute episodes may increase lactate and blood ammonia levels resulting in behavioral changes, neurological symptoms, nausea and vomiting, etc. These symptoms may be transient and only occur after a large protein load.

  • Consider supporting the production of ATP energy with vitamins B1, B2, B3, calcium and lipoic acid.
    • Conversion of alpha-ketoglutarate requires vitamin B6, in addition to the other pathway nutrients.
  • The enzyme that converts alpha-ketoglutarate into succinyl CoA may be inhibited by low NAD+ levels. NAD+ is derived from vitamin B3.
    • Consider supporting NAD+ levels with vitamin B3 and resveratrol.
  • Arsenic and other toxic metals may inhibit the enzyme that breaks down alpha-ketoglutarate into succinyl-CoA.
    • Arsenic may be found in well water, in factory-farmed poultry, alcoholic beverages and as a pesticide contaminant in conventionally-farmed fruits and vegetables. Arsenic exposure can increase alpha-ketoglutarate and pyruvate, while citrate, succinate, and pyroglutamate levels decrease.

2-Oxoglutaric acid is an organic acid that is important for the proper metabolism of all essential amino acids. It is formed in the Krebs cycle, the energy-producing process that occurs in most body cells.

Other names: AKG, α-KG, 2-oxoglutarate, 2OG

2-Oxoglutaric acid is an organic acid that is important for the proper metabolism of all essential amino acids. It is formed in the Krebs cycle, the energy-producing process that occurs in most body cells.

The Krebs cycle (aka Citric Acid cycle) is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins into ATP.

2-Oxoglutaric acid is the nitrogen-free portion of the amino acids known as glutamine and glutamic acid, which is involved in protein synthesis that may play a role in supporting healthy blood glucose levels. 2-Oxoglutaric acid helps maintain normal levels of ammonia in the brain, muscles and kidneys, as well as the body’s nitrogen balance in body tissues and fluids.

2-Oxoglutaric acid is used by cells during growth and in healing from injuries and other wounds, and is especially important in the healing of muscle tissue.

2-Oxoglutaric acid is one of the most important nitrogen transporters in metabolic pathways. The amino groups of amino acids are attached to it (by transamination) and carried to the liver where the urea cycle takes place.

References:

- Alpha-Ketoglutarate: Physiological Functions and Applications [L]

- Urinary alpha-ketoglutarate is elevated in patients with hyperinsulinism-hyperammonemia syndrome. [L]

2-Oxoglutaric
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