Figure 3.

Endogenous formation of reactive persulfide species and its function in 8-nitro-cGMP metabolism. (A) Formation of reactive persulfide species by CBS and CSE. CBS and CSE produce CysSSH as a primary product from cystine, and the following reaction with endogenous thiol compounds forms various reactive persulfide species in vivo; (B) Reactive persulfide species–dependent metabolic pathway regulating 8-nitro-cGMP signaling. The 8-nitro-cGMP reacts with reactive persulfide species to form 8-SH-cGMP with the release of nitrite. An additional reaction between the sulfhydrated metabolite 8-SH-cGMP and ROS results in cGMP formation by oxidative desulfidation, and the cGMP thus formed is then degraded by phosphodiesterase. CBS, cystathionine β-synthase; CSE, cystathionine γ-lyase; Cys, cysteine; CysSSH, cysteine persulfide; GSH, glutathione; cGMP, guanosine 3′,5′-cyclic monophosphate; 8-nitro-cGMP, 8-nitroguanosine 3′,5′-cyclic monophosphate; NO₂⁻, nitrite anion; ROS, reactive oxygen species.