Action of zinc-complexing agents on nicotinamide adenine dinucleotide-linked aldehyde dehydrogenases from yeast and liver

Metal-complexing agents (1,10-phenanthroline (OP), 8-hydroxyquinoline (OHQ), EDTA, and histidine) produce essential activation of yeast aldehyde dehydrogenase (E.C.1.2.1.5), like cysteine and BAL. The extent of enzyme activation varies according to the coenzyme structure. Diethyldithiocarbamate and cyanide are weaker activators, and glycine, glycylglycine, adenine, and cupferron do not stimulate the enzyme activity. Liver aldehyde dehydrogenase (E.C.1.2.1.3) and cysteine-activated yeast aldehyde dehydrogenase are inhibited by OP, OHQ, diethyldithiocarbamate and α,α′-dipyridyl. The instantaneous inhibition is reversible, competitive between chelator and coenzyme and mostly noncompetitive with respect to substrate. The kinetics of inhibition is consistent wih the presence of zinc as an intrinsic constituent of both enzymes. OP, BAL, and other ligands produce time and temperature-dependent progressive inhibition of yeast aldehyde dehydrogenase (but not of liver aldehyde dehydrogenase). This inhibition increases with the specific activity of the enzyme preparation, or the presence of adenosine phosphates, nicotinamide and acetylpyridine dinucleotides, or sodium or ammonium ions. Thiol compounds, other ligands (EDTA, cyanide, OHQ, etc.), pyridine aldehyde dinucleotides, pyrophosphate, zinc, potassium, and rubidium ions prevent or decrease OP irreversible inhibition. The effects of most of ligands as enzyme activators and as enzyme protectors against OP inhibition are closely related, and with cysteine, the relationship is quantitative. Highly purified preparations of yeast aldehyde dehydrogenases contain traces of heavy metals that, by forming inactive enzyme-mercaptides, have apparently a significant role for the enzyme instantaneous activation and for the progressive inhibition by chelators. OP and OHQ increase the sensitivity of yeast aldehyde dehydrogenase toward SH-reagents and decrease that of the liver enzyme.