Chemistry:Alda-1
Template:Drug box 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 ALHD2 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]
References
- ↑ 1.0 1.1 1.2 "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. doi:10.1111/jcmm.13677. PMID 29799157.
- ↑ 2.0 2.1 2.2 "Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart". Science 321 (5895): 1493–5. September 2008. doi:10.1126/science.1158554. PMID 18787169. Bibcode: 2008Sci...321.1493C.
- ↑ 3.0 3.1 "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. doi:10.1016/j.ejphar.2020.173541. PMID 32896553.
- ↑ "Targeting aldehyde dehydrogenase 2: new therapeutic opportunities". Physiological Reviews 94 (1): 1–34. January 2014. doi:10.1152/physrev.00017.2013. PMID 24382882.
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