Arylazido-β-alanine ADP-ribose, a novel irreversible competitive inhibitor of mitochondrial NADH-ubiquinone reductase

Marina V. Frenkin, Alexander Kotlyar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Arylazido-β-alanine ADP-ribose, a photoreactive analogue of ADP-ribose, was synthesized. In the dark, arylazido-β-alanine ADP-ribose acts as a competitive reversible inhibitor of mitochondrial NADH-ubiquinone reductase with a K(i) of 37 μM. Upon photolysis, arylazido-β-alanine ADP-ribose is converted to a potent irreversible active site-directed inhibitor of the enzyme. Photo-induced inhibition of membrane-bound NADH-ubiquinone reductase by arylazido-β-alanine ADP-ribose is incomplete and results in a 20-fold reduction of the NADH oxidase and 2.5-fold reduction of the energy-dependent NAD+ reductase activities. The arylazido-β-alanine ADP-ribose resistant activities (direct and reverse) of the enzyme are characterized by a two orders of magnitude lower affinity to the corresponding substrates compared to those of the uninhibited NADH-ubiquinone reductase. A different kinetic behavior of the inhibited and native enzyme can be explained by invoking the two catalytically competent nucleotide-binding sites model of NADH-ubiquinone reductase. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)139-146
Number of pages8
JournalBiochimica et Biophysica Acta - Bioenergetics
Issue number3
StatePublished - 10 Nov 1999


  • Arylazido-β-alanine ADP-ribose
  • Bovine heart mitochondrion
  • Competitive inhibition
  • NADH-ubiquinone reductase


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