Structure of lactate dehydrogenase inhibitor generated from coenzyme.
Two inhibitors of lactate dehydrogenase generated during NADH storage have been isolated by chromatography. One is a dimer of the dinucleotide where the AMP moiety is unmodified. The other is also generated from NAD+ in the presence of a high concentration of phosphate ions at alkaline pH. This inhibitor was proved to be the addition compound of one phosphate group to position C-4 of the nicotinamide ring of NAD+ by NMR spectroscopy, enzymatic cleavage, and dissociation to NAD+ at neutral pH. This compound is a competitive inhibitor with respect to NAD+ in the presence of the lactate dehydrogenase with a Ki of 2 X 10(-7) M. The interaction of this inhibitor with lactate dehydrogenase is discussed relative to the structure of this enzyme.
D000469:Alkaline Phosphatase; D000818:Animals; D004355:Drug Stability; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D009132:Muscles / Q000201:enzymology; D009243:NAD / Q000031:analogs & derivatives* / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet
D009243:NAD; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases