Small Molecule Signaling Agents: the Integrated Chemistry and Biochemistry of Nitrogen Oxides, Oxides of Carbon, Dioxygen, Hydrogen Sulfide, and Their Derived Species

Overview

Journal Chem Res Toxicol

Publisher American Chemical Society

Specialty Toxicology

Date 2012 Jan 24

PMID 22263838

Citations 129

Authors

Jon M Fukuto

Samantha J Carrington

Dean J Tantillo

Jason G Harrison

Louis J Ignarro

Bruce A Freeman

Andrew Chen

David A Wink

Affiliations

Soon will be listed here.

Abstract

Several small molecule species formally known primarily as toxic gases have, over the past 20 years, been shown to be endogenously generated signaling molecules. The biological signaling associated with the small molecules NO, CO, H₂S (and the nonendogenously generated O₂), and their derived species have become a topic of extreme interest. It has become increasingly clear that these small molecule signaling agents form an integrated signaling web that affects/regulates numerous physiological processes. The chemical interactions between these species and each other or biological targets is an important factor in their roles as signaling agents. Thus, a fundamental understanding of the chemistry of these molecules is essential to understanding their biological/physiological utility. This review focuses on this chemistry and attempts to establish the chemical basis for their signaling functions.

Citing Articles

The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases.

Pan Y, Matsunaga T, Zhang T, Akaike T Biomolecules. 2025; 15(2).

PMID: 40001475 PMC: 11852411. DOI: 10.3390/biom15020172.

Lactoperoxidase catalytically oxidize hydrogen sulfide via intermediate formation of sulfheme derivatives.

Rios-Gonzalez B, Doman A, Ditroi T, Garai D, Crespo L, Gerfen G Redox Biochem Chem. 2024; 8.

PMID: 38993681 PMC: 11238738. DOI: 10.1016/j.rbc.2024.100021.

Carbon Monoxide as a Potential Therapeutic Agent: A Molecular Analysis of Its Safety Profiles.

Bansal S, Liu D, Mao Q, Bauer N, Wang B J Med Chem. 2024; 67(12):9789-9815.

PMID: 38864348 PMC: 11215727. DOI: 10.1021/acs.jmedchem.4c00823.

Oxygen is an essential gasotransmitter directly sensed via protein gasoreceptors.

Anbalagan S Animal Model Exp Med. 2024; 7(2):189-193.

PMID: 38529771 PMC: 11079153. DOI: 10.1002/ame2.12400.

50 shades of oxidative stress: A state-specific cysteine redox pattern hypothesis.

Cobley J Redox Biol. 2023; 67:102936.

PMID: 37875063 PMC: 10618833. DOI: 10.1016/j.redox.2023.102936.

References

Yukl E, de Vries S, Moenne-Loccoz P . The millisecond intermediate in the reaction of nitric oxide with oxymyoglobin is an iron(III)--nitrato complex, not a peroxynitrite. J Am Chem Soc. 2009; 131(21):7234-5. PMC: 2734454. DOI: 10.1021/ja9026924. View

Miranda K, Nagasawa H, Toscano J . Donors of HNO. Curr Top Med Chem. 2005; 5(7):649-64. DOI: 10.2174/1568026054679290. View

Lahiri S, Roy A, Baby S, Hoshi T, Semenza G, Prabhakar N . Oxygen sensing in the body. Prog Biophys Mol Biol. 2005; 91(3):249-86. DOI: 10.1016/j.pbiomolbio.2005.07.001. View

Branzoli U, MASSEY V . Evidence for an active site persulfide residue in rabbit liver aldehyde oxidase. J Biol Chem. 1974; 249(14):4346-9. View

Gladwin M, Grubina R, Doyle M . The new chemical biology of nitrite reactions with hemoglobin: R-state catalysis, oxidative denitrosylation, and nitrite reductase/anhydrase. Acc Chem Res. 2008; 42(1):157-67. DOI: 10.1021/ar800089j. View

Forman H, Fukuto J, Miller T, Zhang H, Rinna A, Levy S . The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal. Arch Biochem Biophys. 2008; 477(2):183-95. PMC: 2590784. DOI: 10.1016/j.abb.2008.06.011. View

Li L, Moore P . An overview of the biological significance of endogenous gases: new roles for old molecules. Biochem Soc Trans. 2007; 35(Pt 5):1138-41. DOI: 10.1042/BST0351138. View

de Beus M, Chung J, Colon W . Modification of cysteine 111 in Cu/Zn superoxide dismutase results in altered spectroscopic and biophysical properties. Protein Sci. 2004; 13(5):1347-55. PMC: 2286766. DOI: 10.1110/ps.03576904. View

Koppenol W . Thermodynamics of reactions involving nitrogen-oxygen compounds. Methods Enzymol. 1996; 268:7-12. DOI: 10.1016/s0076-6879(96)68005-7. View

10.

Giulivi C, Kato K, Cooper C . Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology. Am J Physiol Cell Physiol. 2006; 291(6):C1225-31. DOI: 10.1152/ajpcell.00307.2006. View

11.

Gunaydin H, Houk K . Mechanisms of peroxynitrite-mediated nitration of tyrosine. Chem Res Toxicol. 2009; 22(5):894-8. PMC: 2712443. DOI: 10.1021/tx800463y. View

12.

Sumbayev V, Budde A, Zhou J, Brune B . HIF-1 alpha protein as a target for S-nitrosation. FEBS Lett. 2003; 535(1-3):106-12. DOI: 10.1016/s0014-5793(02)03887-5. View

13.

Pryor W, Squadrito G . The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol. 1995; 268(5 Pt 1):L699-722. DOI: 10.1152/ajplung.1995.268.5.L699. View

14.

Huie R, Padmaja S . The reaction of no with superoxide. Free Radic Res Commun. 1993; 18(4):195-9. DOI: 10.3109/10715769309145868. View

15.

DeMaster E, Quast B, Redfern B, Nagasawa H . Reaction of nitric oxide with the free sulfhydryl group of human serum albumin yields a sulfenic acid and nitrous oxide. Biochemistry. 1995; 34(36):11494-9. DOI: 10.1021/bi00036a023. View

16.

Bartberger M, Liu W, Ford E, Miranda K, Switzer C, Fukuto J . The reduction potential of nitric oxide (NO) and its importance to NO biochemistry. Proc Natl Acad Sci U S A. 2002; 99(17):10958-63. PMC: 123192. DOI: 10.1073/pnas.162095599. View

17.

Mustafa A, Gadalla M, Snyder S . Signaling by gasotransmitters. Sci Signal. 2009; 2(68):re2. PMC: 2744355. DOI: 10.1126/scisignal.268re2. View

18.

Kim-Shapiro D, Gladwin M, Patel R, Hogg N . The reaction between nitrite and hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic vasodilation. J Inorg Biochem. 2004; 99(1):237-46. DOI: 10.1016/j.jinorgbio.2004.10.034. View

19.

Basu S, Azarova N, Font M, King S, Hogg N, Gladwin M . Nitrite reductase activity of cytochrome c. J Biol Chem. 2008; 283(47):32590-7. PMC: 2583304. DOI: 10.1074/jbc.M806934200. View

20.

Gunaydin H, Houk K . Molecular dynamics simulation of the HOONO decomposition and the HO*/NO2* caged radical pair in water. J Am Chem Soc. 2008; 130(31):10036-7. DOI: 10.1021/ja711365e. View