INACTIVATION OF HUMAN ALDEHYDE DEHYDROGENASE BY ISOSORBIDE DINITRATE

摘要: Isosorbide dinitrate inactivated E1 and E2 isozymes of human aldehyde dehydrogenase (EC 1.2.1.3), abolishing both esterase activities. NAD promoted, whereas chloral protected the enzyme from inactivation. The inactivation was irreversible upon dialysis occurred without incorporation 14C-labeled isosorbide dinitrate. Inactivation associated with formation products, isosorbide-2-mononitrate isosorbide-5-mononitrate. At 25 degrees C there were two pathways product formation: a fast pathway, sensitive to inhibitors, slower pathway insensitive inhibitors. simultaneously, inhibited by active site-directed inhibitor bromoacetophenone. 0 degree slow abolished, allowing study catalyzed reaction. isozyme at in single turnover that accounted for 80% catalytic activity loss being major product. No nitrate ever detected; C, nitrite detected but less than stoichiometric amounts. mononitrates also substrates inactivators dehydrogenase. Isosorbide-2-mononitrate had lowest K(i) k3 values when compared other esters isosorbide. Reversibility 2-mercaptoethanol suggested involvement sulfhydryls. appears be mechanism-based involves function