FIG. 2.
S-nitrosothiol and S-nitrosoprotein formation. S-Nitrosothiols (RSNO) are formed when NO• reacts with a low- or high-molecular-weight thiol (RSH) by the exchange of −H for −NO between sulfur groups, a process known as S-transnitrosation. This reaction is catalyzed by cell-surface protein disulfide isomerase (PDI); PDI also facilitates the transport of NO• by localizing the molecule to the cell-membrane space, where it may react with molecular oxygen to generate N2O3, which is a nitrosating agent. In plasma, S-nitrosothiols may react with albumin to generate S-nitrosoalbumin, the most abundant circulating S-nitrosated protein. S-Nitrosoalbumin may also participate in thiol-nitrosothiol exchange with low-molecular-weight thiols such as cysteine. Once S-nitrosocysteine is formed, it is transported across the cell membrane by the System L transporters to reside in the cytoplasm. Here, S-nitrosocysteine may once again participate in thiol-nitrosothiol exchange reactions to generate intracellular S-nitrosothiols. S-Nitrosothiols also play an important role in the formation of S-nitrosoproteins (PrSNO). The majority of S-nitrosoproteins are localized to the mitochondria. Within the mitochondria, NO• synthesized by eNOS or mitochondrial NOS may react with superoxide (•O2−) to form peroxynitrite (ONOO−). Peroxynitrite, in turn, may react with thiol-containing proteins (PrSHs) to yield S-nitrosoproteins or may first react with RSH to generate an S-nitrosothiol, which then facilitates S-nitrosoprotein formation. Adapted from (10). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article at www.liebertonline.com/ars).