ALDH1B1

Aldehyde Dehydrogenase 1 Family Member B1 (ALDH1B1) is a mitochondrial NAD+-dependent oxidoreductase critical for aldehyde detoxification. Common aliases include ALDHX and mitochondrial aldehyde dehydrogenase 1B1. It catalyzes the oxidation of diverse aldehydes—such as acetaldehyde from alcohol metabolism and 4-hydroxynonenal from lipid peroxidation—via a conserved mechanism: an active-site cysteine forms a thiohemiacetal intermediate, which is oxidized to a thioester before hydrolysis to the carboxylic acid product, regenerating the enzyme. ALDH1B1 integrates into pathways like Nrf2-driven antioxidant defense, maintaining cellular redox balance.
Dysregulated ALDH1B1 expression links to multiple pathologies. Overexpression in colorectal, pancreatic, and hepatocellular carcinomas correlates with cancer stem cell phenotypes, chemoresistance, and poor prognosis. It also modulates acetaldehyde-induced oxidative stress in alcohol-related liver disease. Drug development focuses on ALDH1B1 inhibitors as anti-cancer agents; preclinical selective small-molecule inhibitors show promise in reducing tumor growth and enhancing chemotherapy sensitivity, though clinical trials remain in early stages.