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.
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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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3,4-Dihydroxyphenylpropionate, 3-Methyl-4-OH-phenylglycol, 5-Hydroxyindoleacetate, 8-Hydroxy-2-deoxyguanosine, a-Hydroxybutyrate, a-Hydroxyisobutyrate, a-Keto-b-Methylvalerate, a-Ketoadipate, a-Ketoglutarate, a-Ketoisocaproate, a-Ketoisovalerate, a-Ketophenylacetate, Adipate, b-Hydroxybutyrate, b-Hydroxyisovalerate, b-Hydroxypropionate, Benzoate, Cis-Aconitate, Citramalate, Citrate, Creatinine, D-Arabinitol, Formiminoglutamate, Glutarate, Glycerate, Glycolate, Hippurate, Homovanillate, Hydroxymethylglutarate, Indoleacetate, Isocitrate, Isovalerylglycine, Kynurenate, Kynurenate/Quinolinate, Lactate, m-Hydroxyphenylacetate, Malate, Methylmalonate, Orotate, Oxalate, p-Hydroxyphenylacetate, Phenylacetate, Pyroglutamate, Pyruvate, Quinolinate, Suberate, Succinate, Tartarate, Vanilmandelate, Xanthurenate
