Alcohol dehydrogenase (ADH) is a crucial rate-limiting
enzyme in
alcohol metabolism. Our previous research found that ethanol-induced
intracellular extracts of Lactococcus lactis (L. lactis) could enhance alcohol
metabolism in mice, but the responsible compounds remain unidentified.
The study aimed to screen potential ADH-activating peptides from ethanol-induced L. lactis using virtual screening and molecular docking
calculation. Among them, the pentapeptide FAPEG might bind to ADH
through hydrophobic interaction and hydrogen bonds, then enhancing
ADH activity. Spectroscopy analysis further investigated the peptide-enzyme
interaction between FAPEG and ADH, including changes in the amino
acid residue microenvironment and secondary structural alterations.
Furthermore, FAPEG could protect against alcoholic liver injury (ALI)
in mice by reducing blood alcohol concentration, enhancing the activity
of antioxidant and alcohol metabolism enzymes, and attenuating alcohol-induced
hepatotoxicity, which was related to the activation of the Nrf2/keap1/HO-1
signaling pathway. The study provided preliminary evidence that the
generation of ADH-activating peptides in ethanol-induced L. lactis has the potential in preventing ALI in
mice using in silico prediction and in vivo validation approaches.