denitrosylation

Denitrosylation is the biochemical process of removing a nitric oxide (NO) group from S-nitrosylated cysteine residues or other S-nitrosothiols, restoring free thiols and often releasing NO. It serves as the counter-regulatory mechanism to S-nitrosylation and a means to modulate redox signaling in cells.

Enzymatic denitrosylation involves several thiol-based enzymes. The thioredoxin (Trx) and thioredoxin reductase (TrxR) system can denitrosylate S-nitrosylated proteins by transferring the NO moiety to the reductant and regenerating active thiols. Glutaredoxin (Grx) and glutathione (GSH) participate in glutathione-dependent denitrosylation, often through transnitrosation and reduction reactions. S-nitrosoglutathione reductase (GSNOR) degrades S-nitrosoglutathione (GSNO), thereby regulating cellular S-nitrosothiol pools and indirectly promoting denitrosylation by limiting NO donors. Non-enzymatic denitrosylation can occur through reducing agents such as GSH, ascorbate, NADH, and other thiols, particularly under reducing conditions.

Denitrosylation plays a role in regulating signaling pathways, enzyme activity, and protein function, contributing to cellular responses to oxidative and nitrosative stress. Dysregulation of denitrosylation has been associated with cardiovascular and neurodegenerative diseases and cancer, where altered nitrosothiol homeostasis can affect NO signaling and redox balance.