Fig. 2.

Multiple PTM of ALDH2 protein, contributing to its inactivation. Different types of PTM on ALDH2 are illustrated. Most PTMs led to the suppression of ALDH2 activity, although phosphorylation of ALDH2 by the PKCε isoform was shown to stimulate the ALDH2 activity, as recently reviewed [42]. The suppressed activities of ALDH2 and other isozymes, all of which share the 100%-conserved active site Cys residue, likely contribute to increased levels of toxic and carcinogenic acetaldehyde (AcAH) and lipid peroxides (MDA and 4-HNE) following exposure to ethanol, high fat and other toxic compounds. ER stress, mitochondrial dysfunction and tissue injury can be observed in acute and sub-chronic cases. Long-term chronic suppression of ALDH2 and other isozymes can also contribute to fibrosis, cirrhosis and carcinogenesis. The negative sign represents the inactivation of ALDH2 and other isozymes.