How S-nitrosothiols (SNOs) work on the brainstem to control breathing

(a) Hemoglobin is oxygenated in the lungs; one of its cysteine residues is then modified with SNO. (b) Oxygen levels in the brain (and other peripheral tissues) are lower than in blood. Hemoglobin releases its oxygen and changes its shape in a way that ultimately promotes transfer of its NO group to another cysteine residue, in this case on glutathione (c), by transnitrosylation. S-nitrosoglutathione is cleaved by the enzyme gamma-glutamyl transpeptidase in neuronal tissue to form S-nitrosocysteinyl glycine. It is also possible that S-nitrosocysteinyl glycine is then cleaved by a peptidase to produce S-nitroso-L-cysteine. One of these two molecules is then proposed to transnitrosylate a cysteine residue in a target protein in the nucleus tractus solitarius region of the brainstem, regulating the central neuronal circuitry that controls breathing.