The effect of metal ions on mitochondrial pyridine dinucleotide transhydrogenase.
Bovine heart submitochondrial particle transhydrogenase is inhibited by cations in a concentration and pH-dependent manner, and non-energy-linked transhydrogenation is inhibited to a greater extent by metals than the energy-linked reaction. The inhibition of the enzyme by Mg2+ is competitive with the NADP substrate and non-competitive with the NAD substrate. Mg2+ stimulates inactivation of the enzyme by 5,5'-dithiobis(2-nitrobenzoic acid), and protects against thermal and proteolytic inactivation. This suggests that Mg2+ binding in the NADP site alters transhydrogenase to a more thermostable conformation, which is less susceptible to attack by trypsin and more reactive with 5,5'-dithiobis(2-nitrobenzoic acid). Other cation inhibitors mimic Mg2+ in these properties. The order of effectiveness of the inhibitors tested is La3+ greater than Mn2+ greater than Ca2+ congruent to Mg2+ greater than Sr2+ greater than Na+ congruent to K+. This order is described by the Irving-Williams order for the stability of metal-ligand complexes, suggesting that carboxylates or amines may comprise the inhibitory cation binding site.
D000818:Animals; D002413:Cations, Divalent; D002414:Cations, Monovalent; D002417:Cattle; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008929:Mitochondria, Heart / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009250:NADP Transhydrogenases / Q000378:metabolism*; D013367:Submitochondrial Particles / Q000201:enzymology
D002413:Cations, Divalent; D002414:Cations, Monovalent; D004228:Dithionitrobenzoic Acid; D009247:NADH, NADPH Oxidoreductases; D009250:NADP Transhydrogenases