Tracking the Nitric Oxide Signaling Pathway
Both nitric oxide (NO) and hydrogen sulfide (H2S) work as gaseous signaling molecules with comparable physiological effects. Many of the vital concerns concerning the interplay between these two gasotransmitters hinge on their chemical reactivity and the fleeting existence of HSNO, an essential product of the reaction between them. As reported in the journal Angewandte Chemie, a group of scientists stabilized, isolated, and identified 2 of the species connected to these signaling paths with binding to zinc complex.
NO is the central signaling molecule in biology that controls many physiological functions, including vascular dilation, nerve impulses, and cell protection. Remarkably, H2S shows similar effects, relaxing smooth muscle cells involved in vasodilation. HSNO might thus play an essential part in the overlap of these signaling paths. Nonetheless, this very reactive species is so unstable that its biochemistry and distinct reaction paths are complicated to define. HSNO passes conveniently via cell membranes and can nitrosylate proteins, moving its nitrosyl group (-N=O) to other residues, particularly cysteine, which represents an important action in various cellular regulatory mechanisms. At biological pH, HSNO likely exists as the thionitrite anion SNO− that is unstable towards conversion to the perthionitrite anion SSNO−.
Valiallah Hosseininasab, a graduate student in the team led by Timothy H. Warren at Georgetown College (Washington, D.C., U.S.), stabilized the SNO− and SSNO− anions through binding to a unique zinc complex influenced by a typical environment setting for zinc in biology. From a physiological standpoint, zinc is essential to metal associated with many processes, including regulating blood’s pH via the enzyme carbonic anhydrase. Furthermore, molecules involved in nitric oxide signaling, such as H2S and S-nitrosothiols (molecules with an -S-N=O team), promptly react with zinc sulfur bonds that create vital structural units whose adjustment in proteins causes functional change.
The Georgetown team showed that zinc complexes consisting of the SNO− and SSNO− anions could be isolated and defined. Examination of their reactivity patterns revealed fascinating differences in their reactions with thiols (substances with a sulfide group,-SH), ubiquitous antioxidants that aid protect cells from damages. While reactions with perthionitrite produce NO, thionitrite forms either dinitrogen oxide (laughing gas) N2O or S-nitrosothiols, which are ready NO reservoirs. These results imply that the smallest differences throughout physiological signaling paths can cause various output signals that ultimately result from the interaction between NO and H2S.
Originally published by: phys.org
Reference: Valiallah Hosseininasab et al, Thionitrite and Perthionitrite in NO Signaling at Zinc, Angewandte Chemie International Edition (2021). DOI: 10.1002/anie.202104906
