GSNOR

GSNOR, or S-nitrosoglutathione reductase (also known as GSNO reductase), is a cytosolic enzyme that metabolizes S-nitrosoglutathione (GSNO), a stable reservoir of nitric oxide bioactivity. It catalyzes the NADH-dependent reduction of GSNO to glutathione disulfide (GSSG) and ammonia, thereby regulating intracellular levels of S-nitrosothiols and nitric oxide signaling. Through this denitrosylation activity, GSNOR influences the S-nitrosylation state of various proteins and modulates signaling pathways involved in vascular tone, immune responses, and neurotransmission.

In humans, GSNOR is encoded by the ADH5 gene and belongs to the alcohol dehydrogenase/oxidoreductase superfamily, class III. Although historically associated with alcohol metabolism, its physiologic function in nitrosothiol homeostasis is central. The enzyme is typically a cytosolic homodimer that uses NADH as a cofactor and often contains zinc at its catalytic site.

GSNOR homologs are found across a broad range of organisms, including mammals, plants, and many bacteria, reflecting a conserved role in regulating nitrosative stress. By controlling GSNO availability, GSNOR indirectly modulates the protein S-nitrosylation network, thereby affecting processes such as vascular signaling, immune defense, and cellular stress responses.

Clinical and pharmacologic interest centers on manipulating GSNOR activity. Reduced GSNOR function elevates S-nitrosothiol levels and enhances NO signaling, whereas increased activity can dampen nitrosative signaling. Inhibitors of GSNOR are studied as potential therapies to boost endogenous NO signaling, with research focused on respiratory diseases and conditions where enhanced S-nitrosylation may be beneficial.