Alda-1 Explained
Alda-1 is an organic compound that enhances the enzymatic activity of human ALDH2.[1] Alda-1 has been proposed as a potential treatment for the alcohol flush reaction experienced by people with genetically deficient ALDH2.[2]
Mechanism of action
Ethanol is metabolized to acetaldehyde in people, which is then metabolized to acetic acid primarily by ALDH2.[1] People have various ALDH2 alleles. ALDH2*1 is a common allele (wild type), but about 40% of people of East Asian ethnicity have one or two copies of the dominant ALDH2*2 instead, which causes ALDH2 deficiency. If deficient people drink ethanol, they suffer from alcohol flush reaction due to acetaldehyde accumulation.[3]
Four Alda-1 molecules bind to each monomer of ALDH2 tetramer. This enhances NAD+ binding to ALDH2. NAD+ is required by ALDH2 for its enzymatic activity,[4] which is why Alda-1 increases ALDH2 activity by 2.1 fold if ALDH2 is coded by ALDH2*1 and by 11 fold if it is coded ALDH2*2.[2]
History
Chen et al. first reported Alda-1 in 2008.[2] [1] Alda-1 is the first known aldehyde dehydrogenase activator.[3]
Notes and References
- Ma X, Luo Q, Zhu H, Liu X, Dong Z, Zhang K, Zou Y, Wu J, Ge J, Sun A . 6 . Aldehyde dehydrogenase 2 activation ameliorates CCl4 -induced chronic liver fibrosis in mice by up-regulating Nrf2/HO-1 antioxidant pathway . Journal of Cellular and Molecular Medicine . 22 . 8 . 3965–3978 . May 2018 . 29799157 . 6050510 . 10.1111/jcmm.13677 .
- Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley TD, Mochly-Rosen D . Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart . Science . 321 . 5895 . 1493–5 . September 2008 . 18787169 . 2741612 . 10.1126/science.1158554 . 2008Sci...321.1493C .
- Mittal M, Bhagwati S, Siddiqi MI, Chattopadhyay N . A critical assessment of the potential of pharmacological modulation of aldehyde dehydrogenases to treat the diseases of bone loss . European Journal of Pharmacology . 886 . 173541 . November 2020 . 32896553 . 10.1016/j.ejphar.2020.173541 . 221540241 .
- Chen CH, Ferreira JC, Gross ER, Mochly-Rosen D . Targeting aldehyde dehydrogenase 2: new therapeutic opportunities . Physiological Reviews . 94 . 1 . 1–34 . January 2014 . 24382882 . 3929114 . 10.1152/physrev.00017.2013 .
