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The activation of metabolites of nitric oxide synthase by metals is both redox and oxygen dependent: a new feature of nitrogen oxide signaling

The activation of metabolites of nitric oxide synthase by metals is both redox and oxygen dependent: a new feature of nitrogen oxide signaling
The activation of metabolites of nitric oxide synthase by metals is both redox and oxygen dependent: a new feature of nitrogen oxide signaling
Nitrite (NO(2)-), N (G)-hydroxy-L-arginine (NOHA), and hydroxylamine (NH(2)OH) are products of nitric oxide synthase (NOS) activity and can also be formed by secondary reactions of nitric oxide (NO). These compounds are commonly considered to be rather stable and as such to be dosimeters of NO biosynthesis. However, each can be converted via metal-catalyzed reactions into either NO or other reactive nitrogen oxide species (RNOS), such as nitrogen dioxide (NO(2)) and nitroxyl (HNO), which have biologic activities distinct from those of the parent molecules. Consequently, certain aspects of tissue regulation controlled by RNOS may be dictated to a significant extent by metal-dependent reactions, thereby offering unique advantages for cellular and tissue regulation. For instance, because many metal-catalyzed reactions depend on the redox and oxygen status of the cellular environment, such reactions could serve as redox indicators. Formation of RNOS by metal-mediated pathways would confine the chemistry of these species to specific cellular sites. Additionally, such mechanisms would be independent both of NO and NOS, thus increasing the lifetime of RNOS that react with NO. Thus metal-mediated conversion of nitrite, NOHA, and NH(2)OH into biologically active agents may provide a unique signaling mechanism. In this review, we discuss the biochemistry of such reactions in the context of their pharmacologic and biologic implications.
1523-0864
1363-1371
Donzelli, Sonia
05040e2c-6d36-458e-96ad-7585b2aa2605
Switzer, Christopher H.
be8d1041-0a07-4613-9d83-91585bb87b86
Thomas, Douglas D.
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Ridnour, Lisa A.
820d6040-f6c0-41d2-af5c-f44d70f2b255
Espey, Michael Graham
be05250f-de20-48c2-bc05-924c1f572a7c
Isenberg, Jeffrey S.
42b49e83-0b7b-48b0-ae3e-0dc38468f2c4
Tocchetti, Carlo G.
af34254a-8223-41c7-b8f1-da7378c5e65e
King, S. Bruce
5241453a-2323-4e76-a41c-85abc3ebdf46
Lazzarino, Giuseppe
2344efe0-43bc-4781-9f72-451f3d7f407d
Miranda, Katrina M.
128fa814-eb00-472f-a5e7-5657e59ac9b9
Roberts, David D.
74e27116-83e2-4553-929d-4688c31214c3
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Wink, David A.
008b5aec-8c2b-4035-8912-fb6fd530413c
Donzelli, Sonia
05040e2c-6d36-458e-96ad-7585b2aa2605
Switzer, Christopher H.
be8d1041-0a07-4613-9d83-91585bb87b86
Thomas, Douglas D.
b685f80a-b4f5-42fa-b90f-3b7ec1ed6b7a
Ridnour, Lisa A.
820d6040-f6c0-41d2-af5c-f44d70f2b255
Espey, Michael Graham
be05250f-de20-48c2-bc05-924c1f572a7c
Isenberg, Jeffrey S.
42b49e83-0b7b-48b0-ae3e-0dc38468f2c4
Tocchetti, Carlo G.
af34254a-8223-41c7-b8f1-da7378c5e65e
King, S. Bruce
5241453a-2323-4e76-a41c-85abc3ebdf46
Lazzarino, Giuseppe
2344efe0-43bc-4781-9f72-451f3d7f407d
Miranda, Katrina M.
128fa814-eb00-472f-a5e7-5657e59ac9b9
Roberts, David D.
74e27116-83e2-4553-929d-4688c31214c3
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Wink, David A.
008b5aec-8c2b-4035-8912-fb6fd530413c

Donzelli, Sonia, Switzer, Christopher H., Thomas, Douglas D., Ridnour, Lisa A., Espey, Michael Graham, Isenberg, Jeffrey S., Tocchetti, Carlo G., King, S. Bruce, Lazzarino, Giuseppe, Miranda, Katrina M., Roberts, David D., Feelisch, Martin and Wink, David A. (2006) The activation of metabolites of nitric oxide synthase by metals is both redox and oxygen dependent: a new feature of nitrogen oxide signaling. Antioxidants & Redox Signaling, 8 (7-8), 1363-1371. (doi:10.1089/ars.2006.8.1363). (PMID:16910783)

Record type: Article

Abstract

Nitrite (NO(2)-), N (G)-hydroxy-L-arginine (NOHA), and hydroxylamine (NH(2)OH) are products of nitric oxide synthase (NOS) activity and can also be formed by secondary reactions of nitric oxide (NO). These compounds are commonly considered to be rather stable and as such to be dosimeters of NO biosynthesis. However, each can be converted via metal-catalyzed reactions into either NO or other reactive nitrogen oxide species (RNOS), such as nitrogen dioxide (NO(2)) and nitroxyl (HNO), which have biologic activities distinct from those of the parent molecules. Consequently, certain aspects of tissue regulation controlled by RNOS may be dictated to a significant extent by metal-dependent reactions, thereby offering unique advantages for cellular and tissue regulation. For instance, because many metal-catalyzed reactions depend on the redox and oxygen status of the cellular environment, such reactions could serve as redox indicators. Formation of RNOS by metal-mediated pathways would confine the chemistry of these species to specific cellular sites. Additionally, such mechanisms would be independent both of NO and NOS, thus increasing the lifetime of RNOS that react with NO. Thus metal-mediated conversion of nitrite, NOHA, and NH(2)OH into biologically active agents may provide a unique signaling mechanism. In this review, we discuss the biochemistry of such reactions in the context of their pharmacologic and biologic implications.

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More information

Published date: 15 August 2006
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337828
URI: http://eprints.soton.ac.uk/id/eprint/337828
ISSN: 1523-0864
PURE UUID: b05ecbdc-25bb-4fcf-a56a-b311f696ccc6
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 04 May 2012 13:00
Last modified: 15 Mar 2024 03:41

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Contributors

Author: Sonia Donzelli
Author: Christopher H. Switzer
Author: Douglas D. Thomas
Author: Lisa A. Ridnour
Author: Michael Graham Espey
Author: Jeffrey S. Isenberg
Author: Carlo G. Tocchetti
Author: S. Bruce King
Author: Giuseppe Lazzarino
Author: Katrina M. Miranda
Author: David D. Roberts
Author: Martin Feelisch ORCID iD
Author: David A. Wink

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