Role of the general base Glu268 in nitroglycerin bioactivation and mechanism-based superoxide formation by aldehyde dehydrogenase-2
نویسندگان
چکیده
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 (NO) [2]. To elucidate the mechanism of ALDH2-catalyzed GTN bioactivation in relation to the established ALDH2 activities (dehydrogenase, esterase), we compared the function of the wildtype (WT) enzyme with a mutant lacking the general base Glu268 (E268Q).
منابع مشابه
Site-directed mutagenesis of aldehyde dehydrogenase-2 suggests three distinct pathways of nitroglycerin biotransformation.
To elucidate the mechanism underlying reduction of nitroglycerin (GTN) to nitric oxide (NO) by mitochondrial aldehyde dehydrogenase (ALDH2), we generated mutants of the enzyme lacking the cysteines adjacent to reactive Cys302 (C301S and C303S), the glutamate that participates as a general base in aldehyde oxidation (E268Q) or combinations of these residues. The mutants were characterized regard...
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