Alcohol dehydrogenase class 3 (ADH3) (ADH3)

Alcohol dehydrogenase class 3 (ADH3), also widely known as S-nitrosoglutathione reductase (GSNOR) or formaldehyde dehydrogenase, is a highly conserved enzyme that plays a dual role in cellular metabolism and signaling. It is the primary enzyme responsible for the glutathione-dependent detoxification of formaldehyde, converting it into S-formylglutathione to prevent cellular damage (UniProt: P11766). Additionally, ADH3 acts as a master regulator of S-nitrosothiol (SNO) homeostasis by catalyzing the NADH-dependent reduction of S-nitrosoglutathione (GSNO), the most abundant low-molecular-weight S-nitrosothiol and a key reservoir of nitric oxide (NO) bioactivity (PubMed: 15743804). By modulating GSNO levels, the enzyme indirectly controls protein S-nitrosylation, a post-translational modification that influences diverse physiological processes including airway smooth muscle relaxation and immune cell activation (PubMed: 22539131). In therapeutic development, GSNOR inhibitors have been investigated for treating respiratory conditions like asthma and cystic fibrosis, aiming to restore GSNO levels that are often depleted in these diseases (PubMed: 26962877). Beyond the lungs, ADH3 is implicated in cardiovascular health, neuroprotection, and oncology, making it a versatile target for managing inflammatory and metabolic disorders (PubMed: 21854402).

Other names

Formaldehyde dehydrogenaseS-nitrosoglutathione reductaseGSNORADH5Glutathione-dependent formaldehyde dehydrogenase

Inhibition of S-nitrosoglutathione reductase (GSNOR) activity to prevent the breakdown of S-nitrosoglutathione (GSNO), thereby increasing GSNO levels to promote bronchodilation, reduce inflammation, and enhance cystic fibrosis transmembrane conductance regulator (CFTR) function (PubMed: 26962877).