title: Interaction of Mg2+ with human liver aldehyde dehydrogenase. II. Mechanism and site of interaction.
abstract: The dehydrogenase reaction of the cytoplasmic isozyme (E1) of human aldehyde dehydrogenase (EC 1.2.1.3) was inhibited while that of the mitochondrial isozyme (E2) was stimulated by low levels of Mg2+ (up to about 150 microM). However, with respect to esterase activity, Mg2+ had a similar effect on both isozymes in that only the NADH-stimulated reaction was effected. Comparison of coenzyme dissociation constants from the dehydrogenase reaction with the coenzyme stimulation constants from the esterase reactions provided the detailed mechanism of the action of Mg2+. The data indicate that Mg2+ acts similarly to bring about alterations in the activity of both isozymes. With E1, where NADH release is the rate-determining step, Mg2+ inhibits by causing a tighter binding of NADH to the enzyme. With E2, however, the stimulation results from the increased rate of acid release from the ternary complex (rate-determining step for E2) when Mg2+ is also present. These results suggest that three enzyme conformers participate in the dehydrogenase reaction and provide a unified mechanism for the stimulation of the dehydrogenase reaction catalyzed by the E2 isozyme, inhibition of the same reaction catalyzed by the E1 isozyme, and the effects of Mg2+ on the esterase reactions (nonstimulated and coenzyme stimulated) of both isozymes.
mesh_terms: D000444:Aldehyde Dehydrogenase; D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology*; D015636:Magnesium Chloride; D008433:Mathematics; D008930:Mitochondria, Liver / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D007527:Isoenzymes; D015636:Magnesium Chloride; D009243:NAD; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase; D008274:Magnesium