Metabolimix+ (Genova Diagnostics)

a-Ketoadipic Acid

Optimal Result: 0 - 1.7 mmol/mol creatinine.

α-Ketoadipic Acid (AKAA; 2-Oxoadipic acid, 2-Ketoadipic acid) is an organic acid formed from α-aminoadipic acid (which originates with lysine) and also from α-aminomuconic acid (derived from tryptophan).

AKAA metabolizes to form glutaryl-CoA via oxidative decarboxylation. The cofactors needed in this step are Coenzyme A, NAD, thiamine pyrophosphate (vitamin B1), lipoic acid, and vitamin B2.

References:

- Wilson R, Wilson C, Gates S, Higgins J. α-Ketoadipic aciduria: A description of a new metabolic error in lysine-tryptophan degradation. Ped Res. 1975;9(6):522-526.

- Bender DA, Njagi EN, Danielian PS. Tryptophan metabolism in vitamin B6-deficient mice. Br J Nutr. 1990;63(1):27-36.

- Solmonson A, DeBerardinis RJ. Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem. 2018;293(20):7522- 7530.

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

What does it mean if your a-Ketoadipic Acid result is too high?

Elevations in urinary AKAA may reflect enzymatic dysfunction due to nutritional cofactor needs.

Mitochondrial oxidative phosphorylation disorders are also associated with higher levels of AKAA.

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