Inactivation of Aldehyde Dehydrogenase by Disulfiram in the Presence and Absence of Lipoic Acid or Dihydrolipoic Acid: An in Vitro Study

The inhibition of aldehyde dehydrogenase (ALDH) by disulfiram (DSF) in vitro can be prevented and/or reversed by dithiothreitol (DTT), which is a well-known low molecular weight non-physiological redox reagent commonly used in laboratory experiments. These observations inspired us to ask the question whether the inhibition of ALDH by DSF can be preserved or abolished also by dihydrolipoic acid (DHLA), which is the only currently known low molecular weight physiological dithiol in the body of humans and other animals. It can even be metaphorized that DHLA is an “endogenous DTT”. Lipoic acid (LA) is the oxidized form of DHLA. We investigated the inactivation of ALDH derived from yeast and rat liver by DSF in the presence or absence of LA or DHLA. The results clearly show that DHLA is able both to restore and protect ALDH activity blocked by DSF. The proposed mechanism is discussed.