Updating NO^•/HNO interconversion under physiological conditions: A biological implication overview

Azanone (HNO/NO^-), also called nitroxyl, is a highly reactive compound whose biological role is still a matter of debate. A key issue that remains to be clarified regarding HNO and its biological activity is that of its endogenous formation. Given the overlap of the molecular targets and reactivity of nitric oxide (NO•) and HNO, its chemical biology was perceived to be similar to that of NO• as a biological signaling agent. However, despite their closely related reactivity, NO• and HNO's biochemical pathways are quite different. Moreover, the reduction of nitric oxide to azanone is possible but necessarily coupled to other reactions, which drive the reaction forward, overcoming the unfavorable thermodynamic barrier. The mechanism of this NO•/HNO interplay and its downstream effects in different contexts were studied recently, showing that more than fifteen moderate reducing agents react with NO• producing HNO. Particularly, it is known that the reaction between nitric oxide and hydrogen sulfide (H₂S) produces HNO. However, this rate constant was not reported yet. In this work, firstly the NO•/H₂S effective rate constant was measured as a function of the pH. Then, the implications of these chemical (non-enzymatic), biologically compatible, routes to endogenous HNO formation was discussed. There is no doubt that HNO could be (is?) a new endogenously produced messenger that mediates specific physiological responses, many of which were attributed yet to direct NO• effects.