The interaction of liver alcohol dehydrogenase with phenyl adenine dinucleotide, a novel analog of pyridine nucleotide coenzymes.
We have synthesized phenyl adenine dinucleotide (P1-adenosine-5')-P2-(beta-D-ribofuranosylbenzene-5')-pyrophosphate (PhAD), a novel analog of pyridine nucleotide coenzymes. This compound contains a planar aromatic ring, as does NAD+, but lacks a positive charge. PhAD is an inhibitor of horse liver alcohol dehydrogenase, competitive with NADH. PhAD is very similar to NAD+ sterically since both compounds have a planar aromatic ring. However, PhAD resembles NADH in binding to the enzyme because the dissociation constants of both compounds show a parallel increase as the pH is raised, whereas those of NAD+ behave in the opposite manner. These observations indicate that the enzyme differentiates between NAD+ and NADH on the basis of the positive charge on the molecule and not the stereochemical orientation of the reduced nicotinamide ring.
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D006736:Horses; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009243:NAD / Q000031:analogs & derivatives*; D013329:Structure-Activity Relationship
D009243:NAD; D000429:Alcohol Oxidoreductases