ArticleThe Journal of biological chemistry2010
Characterization of the East Asian variant of aldehyde dehydrogenase-2: bioactivation of nitroglycerin and effects of Alda-1.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- ALDH2 gene G487A polymorphism and coronary artery disease: a meta-analysis including 5644 participants.Journal of cellular and molecular medicine · 2018Pooled it
- Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure.The Journal of clinical investigation · 2025Article
- Mechanisms and preventive measures of ALDH2 in ischemia‑reperfusion injury: Ferroptosis as a novel target (Review).Molecular medicine reports · 2025Review
- Protection of retinal function and morphology in MNU-induced retinitis pigmentosa rats by ALDH2: an in-vivo study.BMC ophthalmology · 2020Article
- Alda-1 Attenuates Hyperoxia-Induced Acute Lung Injury in Mice.Frontiers in pharmacology · 2020Article
- Alda-1 attenuates hyperoxia-induced mitochondrial dysfunction in lung vascular endothelial cells.Aging · 2019Article
- Mitochondrial aldehyde dehydrogenase-2 deficiency compromises therapeutic effect of ALDH bright cell on peripheral ischemia.Redox biology · 2017Article
- Human Second Window Pre-Conditioning and Post-Conditioning by Nitrite Is Influenced by a Common Polymorphism in Mitochondrial Aldehyde Dehydrogenase.JACC. Basic to translational science · 2017Article
- Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.Antioxidants & redox signaling · 2015Review
- Mitochondrial reactive oxygen species at the heart of the matter: new therapeutic approaches for cardiovascular diseases.Circulation research · 2015Review
- Human ALDH1B1 polymorphisms may affect the metabolism of acetaldehyde and all-trans retinaldehyde--in vitro studies and computational modeling.Pharmaceutical research · 2015Article
- Effect of aldehyde dehydrogenase 2 gene polymorphism on hemodynamics after nitroglycerin intervention in Northern Chinese Han population.Chinese medical journal · 2015Article
- Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system.Science translational medicine · 2014Article
- Targeting aldehyde dehydrogenase 2: new therapeutic opportunities.Physiological reviews · 2014Review
- Catalytic contribution of threonine 244 in human ALDH2.Chemico-biological interactions · 2013Article
- Molecular characterization of a thermostable aldehyde dehydrogenase (ALDH) from the hyperthermophilic archaeon Sulfolobus tokodaii strain 7.Extremophiles : life under extreme conditions · 2013Article
- Vascular bioactivation of nitroglycerin by aldehyde dehydrogenase-2: reaction intermediates revealed by crystallography and mass spectrometry.The Journal of biological chemistry · 2012Article
- Nitroglycerin use in myocardial infarction patients.Circulation journal : official journal of the Japanese Circulation Society · 2012Review
- ALDH2 activator inhibits increased myocardial infarction injury by nitroglycerin tolerance.Science translational medicine · 2011Article
- Mitochondrial aldehyde dehydrogenase and cardiac diseases.Cardiovascular research · 2010Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The East Asian variant of mitochondrial aldehyde dehydrogenase (ALDH2) exhibits significantly reduced dehydrogenase, esterase, and nitroglycerin (GTN) denitrating activities. The small molecule Alda-1 was reported to partly restore low acetaldehyde dehydrogenase activity of this variant. In the present study we compared the wild type enzyme (ALDH2*1) with the Asian variant (ALDH2*2) regarding GTN bioactivation and the effects of Alda-1. Alda-1 increased acetaldehyde oxidation by ALDH2*1 and ALDH2*2 approximately 1.5- and 6-fold, respectively, and stimulated the esterase activities of both enzymes to similar extent as the coenzyme NAD. The effect of NAD was biphasic with pronounced inhibition occurring at > or = 5 mM. In the presence of 1 mM NAD, Alda-1 stimulated ALDH2*2-catalyzed ester hydrolysis 73-fold, whereas the NAD-stimulated activity of ALDH2*1 was inhibited because of 20-fold increased inhibitory potency of NAD in the presence of the drug. Although ALDH2*2 exhibited 7-fold lower GTN denitrating activity and GTN affinity than ALDH2*1, the rate of nitric oxide formation was only reduced 2-fold, and soluble guanylate cyclase (sGC) activation was more pronounced than with wild type ALDH2 at saturating GTN. Alda-1 caused slight inhibition of GTN denitration and did not increase GTN-induced sGC activation in the presence of either variant. The present results indicate that Alda-1 stimulates established ALDH2 activities by improving NAD binding but does not improve the GTN binding affinity of the Asian variant. In addition, our data revealed an unexpected discrepancy between GTN reductase activity and sGC activation, suggesting that GTN denitration and bioactivation may reflect independent pathways of ALDH2-catalyzed GTN biotransformation.
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