Enzymatic requirement for cyanamide inactivation of rat liver aldehyde dehydrogenase

Biochem Pharmacol. 1985 Apr 15;34(8):1197-204. doi: 10.1016/0006-2952(85)90495-2.

Abstract

The in vitro inactivation of aldehyde dehydrogenase (ALDH) by cyanamide in rat liver slices, in intact mitochondria, and at various stages of purity was characterized. Low-Km ALDH was more susceptible to cyanamide inactivation than was the high-Km form. In addition, the presence of NAD or NADH was necessary for cyanamide inhibition of the ALDH activity. Cyanamide at low concentrations required enzymatic conversion to a reactive derivative that could inhibit ALDH. The data in this study are consistent with the suggestion of DeMaster et al. [Biochem. biophys. Res. Commun., 122, 358 (1984)] that catalase is the cyanamide-converting enzyme. An inhibitor of catalase activity, malonate, decreased the rate of cyanamide inactivation of ALDH in intact mitochondria. Furthermore, affinity chromatography-purified ALDH, free of catalase activity, was not susceptible to cyanamide inactivation. This affinity-purified ALDH was only inactivated by high concentrations of cyanamide. Thus, an alternative pathway for ALDH inactivation may exist in which enzymatic modification of cyanamide is not necessary. It is more likely, however, that a contaminating enzyme in the ALDH preparation is capable of activating cyanamide.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehyde Dehydrogenase / antagonists & inhibitors*
  • Aldehyde Dehydrogenase / isolation & purification
  • Animals
  • Biotransformation
  • Catalase / antagonists & inhibitors
  • Chloral Hydrate / metabolism
  • Chloral Hydrate / pharmacology
  • Coenzymes / metabolism
  • Cyanamide / metabolism
  • Cyanamide / pharmacology*
  • Cyanides / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Liver / enzymology*
  • Male
  • Malonates / pharmacology
  • Mitochondria, Liver / enzymology
  • Models, Chemical
  • NAD / metabolism
  • Rats
  • Time Factors

Substances

  • Coenzymes
  • Cyanides
  • Malonates
  • NAD
  • Chloral Hydrate
  • Cyanamide
  • malonic acid
  • Catalase
  • Aldehyde Dehydrogenase