title: Inhibition of horse liver alcohol dehydrogenase and rabbit muscle lactate dehydrogenase by phenylhydrazine.
abstract: The activity of horse liver alcohol dehydrogenase was inhibited by phenylhydrazine. Kinetic experiments showed that this compound produced linear competitive inhibition with respect to NAD+ and linear noncompetitive inhibition with respect to ethanol. These results suggested that the inhibitor competes with NAD+ for the coenzyme binding site of alcohol dehydrogenase, forming a dead-end complex with the free form of the enzyme. A Ki value of 393 +/- 51 microM was estimated for the enzyme-inhibitor complex. Further evidence for this mechanism of inhibition arose from the fact that the same kind of inhibition was found for rabbit muscle lactate dehydrogenase. The Ki value for the lactate dehydrogenase-phenylhydrazine complex was 43.41 +/- 2.10 mM. The significant difference between these Ki values is explained in terms of known differences in hydrophobicity of the nicotinamide binding region in the two enzymes.
authors.affiliation: Departamento de Bioquimica, Universidade Federal do Rio de Janeiro, Brasil.
authors.forename: L M
authors.initials: LM
authors.lastname: Paiva
authors.forename: G F
authors.initials: GF
authors.lastname: Pinto
authors.forename: E G
authors.initials: EG
authors.lastname: Oestreicher
mesh_terms: D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D000818:Animals; D000431:Ethanol / Q000378:metabolism; D006736:Horses; D006834:Hydrazines / Q000494:pharmacology; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology*; D009132:Muscles / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010659:Phenylhydrazines / Q000494:pharmacology*; D011817:Rabbits; D012663:Semicarbazides / Q000494:pharmacology
chemical_list: D006834:Hydrazines; D010659:Phenylhydrazines; D012663:Semicarbazides; C030299:phenylhydrazine; D009243:NAD; C029424:hydrazine; C010059:carbamylhydrazine; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D007770:L-Lactate Dehydrogenase