Is aldehyde dehydrogenase inhibited by sulfur compounds? In vitro and in vivo studies.

Aldehyde dehydrogenase (ALDH) catalyzes the critical step of ethanol metabolism, i.e. transformation of toxic acetaldehyde to acetic acid. It is a redox sensitive protein with the key Cys in its active site. Recently, it has been documented that activity of some proteins can be modified by sulfur-containing molecules called reactive sulfur species leading to the formation of hydro- persulfides. The aim of the present study was to examine whether ALDH activity can be modified in this way. Studies were performed in vitro using yeast ALDH and various reactive sulfur species, including Na2S, GSSH, K2Sx, Na2S2O3, and garlic-derived allyl sulfides. The effect of garlic-derived trisulfide on ALDH activity was also studied in vivo in the rat liver. The obtained results clearly demonstrated that ALDH could be regulated by sulfur species which inhibited its enzymatic activity. The results also suggested that not H2S but polysulfides or hydropersulfides were the oxidizing species responsible for this modification. This process was easily reversible by reducing agents. After the treatment with polysulfides or hydropersulfides the level of protein-bound sulfur increased, while the activity of the enzyme dramatically decreased. Moreover, the study demonstrated that ALDH activity was inhibited in vivo in the rat liver after garlic-derived trisulfide administration. This is the first study reporting the regulation of ALDH activity by sulfane sulfur species and the results suggest that it leads to the inhibition of the enzyme.