Γ-Aminobutyraldehyde Explained

γ-Aminobutyraldehyde (ABAL, GABAL), also known as 4-aminobutanal, 4-aminobutyraldehyde, or GABA aldehyde, is a metabolite of putrescine and a biological precursor of γ-aminobutyric acid (GABA).^{[1] [2]} It can be converted into GABA by the actions of diamine oxidase (DAO) and aminobutyraldehyde dehydrogenase (ABALDH) (e.g., ALDH9A1). Putrescine is converted into ABAL via monoamine oxidase B (MAO-B).^{[3] [4] [5]} However, biosynthesis of GABA from polyamines like putrescine is a minor metabolic pathway in the brain.

The related compound γ-hydroxybutyraldehyde (GHBAL) is a prodrug of γ-hydroxybutyric acid (GHB) as well as a metabolic intermediate in the conversion of 1,4-butanediol (1,4-BD) into GHB.^{[6] [7]} However, aliphatic aldehydes like GHBAL are caustic, strong-smelling, and foul-tasting, and ingestion is likely to be unpleasant and result in severe nausea and vomiting.

See also

• N-Acetyl-γ-aminobutyraldehyde (N-acetyl-GABAL)

Notes and References

1. Book: Rashmi . Deo . Zanan . Rahul . John . Sheeba . Khandagale . Kiran . Nadaf . Altafhusain . Studies in Natural Products Chemistry . γ-Aminobutyric Acid (GABA): Biosynthesis, Role, Commercial Production, and Applications . Elsevier . 57 . 2018 . 978-0-444-64057-4 . 10.1016/b978-0-444-64057-4.00013-2 . 413–452 . Alternate pathways of GABA synthesis from putrescine and other polyamines have also been reported [207–211]. Here, γ-aminobutyraldehyde, an intermediate from polyamine degradation reaction via combined activities of diamine oxidase (DAO, E.C. 1.4.3.6) and 4-aminobutyraldehyde dehydrogenase (ABALDH), leads to the synthesis of GABA [205,212,213]. In response to abiotic stresses, GABA is also reported to be synthesized from proline via D1-pyrroline intermediate formation [47,205,214] and also by a nonenzymatic reaction [214]. However, GABA synthesis from polyamine pathways is minor in the brain, [215] although they play a significant role in the developing brain [216] and retina [217]. But GABA can be formed from putrescine in the mammalian brain [218]..
2. Shelp BJ, Bozzo GG, Trobacher CP, Zarei A, Deyman KL, Brikis CJ . Hypothesis/review: contribution of putrescine to 4-aminobutyrate (GABA) production in response to abiotic stress . Plant Sci . 193-194 . 130–135 . September 2012 . 22794926 . 10.1016/j.plantsci.2012.06.001 .
3. Nam MH, Sa M, Ju YH, Park MG, Lee CJ . Revisiting the Role of Astrocytic MAOB in Parkinson's Disease . Int J Mol Sci . 23 . 8 . April 2022 . 4453 . 35457272 . 9028367 . 10.3390/ijms23084453 . free .
4. Benedetti MS, Dostert P . Contribution of amine oxidases to the metabolism of xenobiotics . Drug Metab Rev . 26 . 3 . 507–535 . 1994 . 7924902 . 10.3109/03602539408998316 . MAO also catalyses the deamination of a natural brain constituent, monoacetyl-putrescine, producing y-acetylaminobutyraldehyde, which in turn participates in the formation of brain GABA [13]..
5. Cho HU, Kim S, Sim J, Yang S, An H, Nam MH, Jang DP, Lee CJ . Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis . Exp Mol Med . 53 . 7 . 1148–1158 . July 2021 . 34244591 . 8333267 . 10.1038/s12276-021-00646-3 .
6. Felmlee MA, Morse BL, Morris ME . γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology . AAPS J . 23 . 1 . 22 . January 2021 . 33417072 . 8098080 . 10.1208/s12248-020-00543-z .
7. Tay E, Lo WK, Murnion B . Current Insights on the Impact of Gamma-Hydroxybutyrate (GHB) Abuse . Subst Abuse Rehabil . 13 . 13–23 . 2022 . 35173515 . 8843350 . 10.2147/SAR.S315720 . free .