a-Ketoglutaric Acid

Optimal Result: 4 - 52 mmol/mol creatinine.

Isocitric Acid is converted to α-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:

- Wu N, Yang M, Gaur U, Xu H, Yao Y, Li D. Alpha-Ketoglutarate: Physiological Functions and Applications. Biomol Ther (Seoul). 2016;24(1):1-8.

- Dougherty FE. Metabolic testing in mitochondrial disease. Paper presented at: Seminars in neurology2001.

- Tretter L, Adam-Vizi V. Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philos Trans R Soc Lond B Biol Sci. 2005;360(1464):2335-2345.

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

Low levels of α-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 result is too high?

Elevations can be seen with nutrient cofactor deficiencies needed for the enzymatic conversion of α-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.

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