Nitrosylaatio

Nitrosylaatio, known in English as S-nitrosylation, refers to a covalent modification in which a nitric oxide (NO) group is added to a thiol group of cysteine residues in proteins, forming an S-nitrosothiol (RS-NO). The term also covers nitrosylation of metal centers in metalloproteins, where NO binds to a metal ion to form a metal–nitrosyl complex. The reaction is influenced by the cellular redox state and can occur via direct interaction of NO with thiolates, formation of nitrosating species such as N2O3, or through transnitrosylation from preformed S-nitrosothiols.

Biological significance of nitrosylaatio lies in its role as a reversible regulatory mechanism for protein function. S-nitrosylation can alter enzyme activity, protein–protein interactions, localization, and stability, thereby participating in signaling pathways related to vasodilation, neurotransmission, and immune responses. Denitrosylation processes, mediated by enzymes such as thioredoxin and glutaredoxin systems and via the GSNO reductase pathway, restore the unmodified state and help maintain redox balance. Dysregulation of nitrosylaatio is associated with nitrosative stress and has been linked to cardiovascular disease, neurodegeneration, and inflammatory conditions.

Occurrence and examples: NO produced by nitric oxide synthases can initiate nitrosylaatio, and NO may activate soluble guanylate cyclase through metal nitrosylation. Many cysteine-containing proteins undergo S-nitrosylation across tissues, and transnitrosylation from donors like S-nitrosoglutathione (GSNO) can propagate the modification.

Detection and study: Methods include the biotin-switch assay and mass spectrometry–based approaches, each with limitations regarding specificity and context.