The NO-heme signaling hypothesis.

The NO-heme signaling hypothesis.
Free Radic Biol Med. 2017 Sep 03;:
Authors: Kleschyov AL
Abstract
While the biological role of nitric oxide (NO) synthase (NOS) is appreciated, several fundamental aspects of the NOS/NO-related signaling pathway(s) remain incompletely understood. Canonically, the NOS-derived NO diffuses through the (inter)cellular milieu to bind the prosthetic ferro(Fe(2+))-heme group of the soluble guanylyl cyclase (sGC). The formation of ternary NO-ferroheme-sGC complex results in the enzyme activation and accelerated production of the second messenger, cyclic GMP. This paper argues that cells dynamically generate mobile/exchangeable NO-ferroheme species, which activate sGC and regulate the function of some other biomolecules. In contrast to free NO, the mobile NO-ferroheme may ensure safe, efficient and coordinated delivery of the signal within and between cells. The NO-heme signaling may contribute to a number of NOS/NO-related phenomena (e.g. nitrite bioactivity, selective protein S-(N-)nitrosation, endothelium and erythrocyte-dependent vasodilation, some neural and immune NOS functions) and predicts new NO-related discoveries, diagnostics and therapeutics.
PMID: 28877508 [PubMed - as supplied by publisher]

Source: Free Radical Biology and Medicine - September 3, 2017 Category: Biology Authors: Kleschyov AL Tags: Free Radic Biol Med Source Type: research