Alcohol dehydrogenase class-3 (glutathione-dependent formaldehyde dehydrogenase) (ADH5)

Alcohol dehydrogenase class-3 (ADH5) is a human enzyme encoded by the ADH5 gene, and is a member of the alcohol dehydrogenase family. It operates as a homodimer and is best known for its role as a glutathione-dependent formaldehyde dehydrogenase, catalyzing the oxidation of S-hydroxymethyl-glutathione adducts, thus protecting against formaldehyde toxicity—a carcinogenic and cytotoxic metabolite. ADH5 further acts as S-nitrosoglutathione reductase (GSNOR), regulating nitric oxide signaling and protein S-nitrosylation. These functions are integral to cellular homeostasis, impacting detoxification, DNA repair, airway reactivity, and cardiovascular and immune responses. Deficiency or altered activity of ADH5 is linked to increased risk for cancer, inflammatory conditions (including asthma), Fanconi anemia, and disorders involving redox imbalance. While not directly a drug target in mainstream clinical therapy, ADH5 is actively researched for its biomarker and therapeutic potential, and the instability of its recombinant protein has posed technical challenges.

Other names

Alcohol dehydrogenase 5Alcohol dehydrogenase class chi chainADH-3ADHXFDHFALDHGSH-FDHS-(hydroxymethyl)glutathione dehydrogenaseS-nitrosoglutathione reductaseGlutathione-dependent formaldehyde dehydrogenaseFormaldehyde dehydrogenaseGSNORHEL-S-60p

GSNOR antagonists/inhibitors (increase S-nitrosylation by inhibiting nitrosoglutathione reduction, modulating redox and NO signaling) Formaldehyde scavengers (reduce substrate load, modulating ADH5 activity indirectly)