Mechanisms of action of histidinol dehydrogenase and UDP-Glc dehydrogenase. Evidence that the half-reactions proceed on separate subunits.
Histidinol dehydrogenase and UDP-Glc dehydrogenase catalyze 4-electron dehydrogenations that convert primary alcohol groups to the corresponding acids. Both reactions proceed in two distinct steps involving the oxidation of the primary alcohol to a bound form of the intermediate aldehyde, followed by oxidation of this to the corresponding acid. The enzymes have subunit structure, the former is made up of two subunits and the latter of six (beef liver enzyme). Evidence is presented that the two half-reactions proceed independently of the overall reaction. Histidinol dehydrogenase preparations that approach total dissociation into subunits also approach total inhibition of the overall reaction, while the second half reaction is completely unaffected and 50% of the first half-reaction survives. Further, the fraction of overall activity surviving in partially dissociated preparations follows the weight fraction of residual dimer. UDP-Glc dehydrogenase behaves in an analogous fashion. These data are interpreted on the basis that both enzymes function by carrying out first oxidation step at a site on one subunit and then pass the intermediate to a vicinal site on the adjacent subunit, where the reaction is completed.
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism*; D002417:Cattle; D006641:Histidinol; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D046911:Macromolecular Substances; D010084:Oxidation-Reduction; D012486:Salmonella typhimurium / Q000201:enzymology; D013401:Sugar Alcohol Dehydrogenases / Q000302:isolation & purification; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000378:metabolism*
D046911:Macromolecular Substances; D006641:Histidinol; D000429:Alcohol Oxidoreductases; D002237:Carbohydrate Dehydrogenases; D013401:Sugar Alcohol Dehydrogenases; D014533:Uridine Diphosphate Glucose Dehydrogenase