Bioactivation of nitroglycerin by the East Asian variant of aldehyde dehydrogenase-2
نویسندگان
چکیده
Background The East Asian variant of mitochondrial aldehyde dehydrogenase (ALDH2) exhibits significantly reduced dehydrogenase, esterase and nitroglycerin (GTN) reductase activities [1]. The small molecule Alda-1 was reported to partly restore low acetaldehyde dehydrogenase activity of this variant [2]. In the present study we compared the wild-type enzyme (ALDH2*1) with the East Asian variant (ALDH2*2) regarding GTN bioactivation and effects of Alda-1.
منابع مشابه
Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans.
OBJECTIVE Nitrates are used widely in clinical practice. However, the mechanism underlying the bioactivation of nitrates to release NO remains unclear. Recent animal data suggest that mitochondrial aldehyde dehydrogenase (ALDH2) plays a central role in nitrate bioactivation, but its role in humans is not known. We investigated the role of ALDH2 in the vascular effects of nitroglycerin (NTG) in ...
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Background Mitochondrial aldehyde dehydrogenase (ALDH2) plays an essential role in nitroglycerin (GTN) bioactivation, resulting in formation of nitric oxide (NO) or a related activator of soluble guanylate cyclase (sGC) and consequently in cGMP-mediated vasorelaxation [1]. ALDH2 denitrates GTN to 1,2-glyceryl dinitrate (1,2-GDN) and nitrite but also catalyzes reduction of GTN to nitric oxide (N...
متن کاملVascular bioactivation of nitroglycerin is catalyzed by cytosolic aldehyde dehydrogenase-2.
RATIONALE According to general view, aldehyde dehydrogenase-2 (ALDH2) catalyzes the high-affinity pathway of vascular nitroglycerin (GTN) bioactivation in smooth muscle mitochondria. Despite having wide implications to GTN pharmacology and raising many questions that are still unresolved, mitochondrial bioactivation of GTN in blood vessels is still lacking experimental support. OBJECTIVE In t...
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Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN) to yield nitric oxide (NO) or a related species that activates soluble guanylate cyclase (sGC), resulting in cGMP-mediated vasodilation. Accordingly, established ALDH2 inhibitors attenuate GTN-induced vasorelaxation in vitro and in vivo. However, the ALDH2 hypothesis has not been reconc...
متن کاملEast asian variant of aldehyde dehydrogenase 2 is associated with coronary spastic angina: possible roles of reactive aldehydes and implications of alcohol flushing syndrome.
BACKGROUND Coronary spastic angina (CSA) is a common disease among East Asians, including Japanese. The prevalence of alcohol flushing syndrome associated with deficient activity of the variant aldehyde dehydrogenase 2 (ALDH2*2) genotype is prevalent among East Asians. We examined whether CSA is associated with the ALDH2*2 genotype in Japanese. METHODS AND RESULTS The study subjects consisted...
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