Metabolic Analysis Markers (Urine)

a-Ketoglutaric Acid (AKG)

Optimal Result: 4 - 52 mmol/mol creatinine.

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

Alpha-Ketoglutarate 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.

AKG (alpha-ketoglutarate) 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. Alpha-ketoglutarate (AKG) 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.

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

α-Ketoglutarate 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.

Isocitric Acid is converted to a-ketoglutaric acid using the enzyme isocitrate dehydrogenase. Alphaketoglutarate is a rate-determining intermediate in the Citric Acid Cycle and provides an important source of glutamine and glutamate that stimulates protein synthesis and bone tissue formation, inhibits protein degradation in muscle, and constitutes an important metabolic fuel for cells of the gastrointestinal tract. Alpha-ketoglutaric acid is then converted to Succinyl CoA using the enzyme alpha-ketoglutarate dehydrogenase. This enzyme complex is very similar to the pyruvate dehydrogenase complex with similar nutrient cofactor needs.

References:

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

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

What does it mean if your a-Ketoglutaric Acid (AKG) result is too low?

Low levels of a-ketoglutarate may reflect lack of precursors higher up from enzymatic dysfunction due to lack of nutritional cofactors, genetic defects, or toxin exposures.

What does it mean if your a-Ketoglutaric Acid (AKG) result is too high?

- Elevations can be seen with nutrient cofactor deficiencies needed for the enzymatic conversion of a-ketoglutarate such as: vitamin B3, zinc, magnesium, and manganese.

- Higher levels are seen in mitochondrial oxidative phosphorylation disorders and mitochondrial dysfunction.

- Genetic abnormalities with the enzyme itself can also limit conversion of alpha-ketoglutarate, causing elevations.

- High urine levels of alpha-KG can be found in people with hyperinsulinism-hyperammonemia syndrome (HHS).

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