Catalysis of S-nitrosothiols formation by serum albumin: The mechanism and implication in vascular control

Nitric oxide (NO(⋅)) is a short-lived physiological messenger. Its various biological activities can be preserved in a more stable form of S-nitrosothiols (RS-NO). Here we demonstrate that at physiological NO(⋅) concentrations, plasma albumin becomes saturated with NO(⋅) and accelerates formation of low-molecular-weight (LMW) RS-NO in vitro and in vivo. The mechanism involves micellar catalysis of NO(⋅) oxidation in the albumin hydrophobic core and specific transfer of NO(+) to LMW thiols. Albumin-mediated S-nitrosylation and its vasodilatory effect directly depend on the concentration of circulating LMW thiols. Results suggest that the hydrophobic phase formed by albumin serves as a major reservoir of NO(⋅) and its reactive oxides and controls the dynamics of NO(⋅)-dependant processes in the vasculature.