a-­Aminoadipic Acid (Plasma)

Optimal Result: 0 - 4.8 nmol/ML.

- An intermediate metabolite of lysine metabolism, produced primarily under oxidative stress (metal-catalyzed oxidation).

- In adolescents, α-aminoadipic acid was associated with adipogenesis and insulin resistance.

- Higher plasma α-aminoadipic acid was associated with a 4-fold risk of future diabetes and identified risk up to 12 years before the onset of overt disease.

- BCAAs, cystine, α-aminoadipic acid, phenylalanine, and leucine + lysine were significantly increased in obesity, T2D, and with worsening health.

Alpha-aminoadipic acid (also known as 2-aminoadipic acid) is an intermediary biomarker of lysine and tryptophan metabolism. The further metabolism of alpha-aminoadipic acid to alpha-ketoadipic acid requires vitamin B6.

Plasma alpha-aminoadipic acid is strongly associated with the risk of developing diabetes as seen in an assessment of the Framingham Heart Study data. Circulating levels were found to be elevated for many years prior to the onset of diabetes. Preclinical data shows it may also play a role in oxidation and atherosclerotic plaque formation.

References:

- Goh DL, Patel A, Thomas GH, et al. Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). Molec Genet Metab. 2002;76(3):172-180.

- Wang TJ, Ngo D, Psychogios N, et al. 2-Aminoadipic acid is a biomarker for diabetes risk. J Clin Invest. 2013;123(10):4309- 4317.

- Lin H, Levison BS, Buffa JA, et al. Myeloperoxidase-mediated protein lysine oxidation generates 2-aminoadipic acid and lysine nitrile in vivo. Free Rad Biol Med. 2017;104:20-31.

- Przyrembel H, Bachmann D, Lombeck I, et al. Alphaketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies. Clin Chim Acta. 1975;58(3):257-269.

- Hagen J, te Brinke H, Wanders RJ, et al. Genetic basis of alpha-aminoadipic and alpha-ketoadipic aciduria. J Inherit Metab Dis. 2015;38(5):873-879.

- Danhauser K, Sauer SW, Haack TB, et al. DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria. Am J Human Gen. 2012;91(6):1082-1087.

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

Low levels of this metabolite can be seen when it’s precursors, lysine and tryptophan, are also low. There is no known clinical significance of low levels of alpha-aminoadipic acid.

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

- Higher plasma α-aminoadipic acid was associated with a 4-fold risk of future diabetes and identified risk up to 12 years before the onset of overt disease.

- BCAAs, cystine, α-aminoadipic acid, phenylalanine, and leucine + lysine were significantly increased in obesity, T2D, and with worsening health.

The excretion of alpha-aminoadipic acid correlates well with lysine intake. Elevations of alpha-aminoadipic acid may be due to rate limitations of downstream enzymes that require nutrient cofactors including vitamin B2, B6, B12, and choline. Lastly, alpha-aminoadipic aciduria is an extremely rare inborn error of metabolism.

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