Comparing the chemical biology of NO and HNO

Abstract

For the past couple of decades nitric oxide (NO) and nitroxyl (HNO) have been extensively studied due to the important role they play in many physiological and/or pharmacological processes. Many researchers have reported important signaling pathways as well as mechanisms of action of these species, showing direct and indirect effects depending on the environment. Both NO and HNO can react with, among others, metals, proteins, thiols and heme proteins via unique and distinct chemistry leading to improvement of some clinical conditions. Understanding the basic chemistry of NO and HNO and distinguishing their mechanisms of action as well as methods of detection are crucial for understanding the current and potential clinical applications. In this review, we summarize some of the most important findings regarding NO and HNO chemistry, revealing some of the possible mechanisms of their beneficial actions.

Biological signaling by small inorganic molecules

“…NO can interact with a number of other heme proteins including hemoglobin, cyclooxygenase, cytochrome P450 and cytochrome c oxidase [126, 127]. NO can either bind directly to the iron center or can interact with other bound ligands.…”

“…NO has a higher affinity for Fe 2+ compared to Fe 3+ . Several summaries of rate constants for Fe 2+ and Fe 3+ heme interactions have been reported [126, 127, 132, 133]. A quick rule of thumb for the flux of NO required for activation is to take the reciprocal of the K eq , which is k on / k off .…”

Regulation of pancreatic β-cell survival by nitric oxide

“…4,27 When NO reacts with O 2 •-, they produce peroxynitrite (ONOO -), which provokes oxidative of Mcl-1, which depends on apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase (Ask-1/Jnk) activation. 56,58,59 In other cell types, NO induces apoptosis through the activation of ASK-1.…”

“…Extensive information about these reactions has been compiled by Dr. David Wink at NCBI in Bethesda, MD USA. 22,27,28 On the other hand, the direct effects of NO are related to fast and direct reactions between NO and target molecules. 22,29 These effects generally regulate physiological processes necessary to maintain cell viability.…”

Nitric oxide releasing-dendrimers: an overview

“…NO can be administered in gaseous form (respiratory route) in specific cases (Serafim et al, 2012), but this compound is known to react with a wide number of molecules (proteins, thiols, heme proteins, metals and others) and also can be oxidized in solution to NO 2 by O 2 (Fukuto et al, 2012;Toledo, Augusto, 2012). In addition, the NO lifetime in biological media varies from 10 ms to 1 sec (Thomas et al, 2001;Flores-Santana et al, 2009). Furthermore local lack or excess of NO can be deleterious for biological systems.…”