Guanylate cyclase and the ⋅NO/cGMP signaling pathway
Open accessAbstract
Signal transduction with the diatomic radical nitric oxide (NO) is involved in a number of important physiological processes, including smooth muscle relaxation and neurotransmission. Soluble guanylate cyclase (sGC), a heterodimeric enzyme that converts guanosine triphosphate to cyclic guanosine monophosphate, is a critical component of this signaling pathway. sGC is a hemoprotein; it is through the specific interaction of NO with the sGC heme that sGC is activated. Over the last decade, much has been learned about the unique heme environment of sGC and its interaction with ligands like NO and carbon monoxide. This review will focus on the role of sGC in signaling, its relationship to the other nucleotide cyclases, and on what is known about sGC genetics, heme environment and catalysis. The latest understanding in regard to sGC will be incorporated to build a model of sGC structure, activation, catalytic mechanism and deactivation.
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The high affinity and rapid binding of NO to ferrous heme are important biologically for regulation of mitochondrial respiration at CcOx.
“The high affinity and rapid binding to ferrous heme are important biologically for the activation of sGC to generate the second messenger cGMP and the regulation of mitochondrial respiration at CcOx (9–16).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [11]
The high affinity and rapid binding of NO to ferrous heme are important biologically for activation of sGC to generate cGMP.
“The high affinity and rapid binding to ferrous heme are important biologically for the activation of sGC to generate the second messenger cGMP and the regulation of mitochondrial respiration at CcOx (9–16).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [11]
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Nitric oxide donors: chemical activities and biological applications
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- Authors
- Denninger, J. W., & Marletta, M. A.
- Affiliations
- University of Michigan (US)
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 1411
- Issue
- 2-3
- Pages
- 334-350
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2071293996
- Cited by
- 1,040
- References
- 123
- Citations by year
- 2026: 13 · 2025: 30 · 2024: 29 · 2023: 41 · 2022: 38 · 2021: 29 · 2020: 35 · 2019: 41 · 2018: 49 · 2017: 35 · 2016: 41 · 2015: 30 · 2014: 35 · 2013: 29 · 2012: 33
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- soluble guanylate cyclase, nitric oxide signaling, cGMP signaling, heme proteins, carbon monoxide, smooth muscle relaxation, neurotransmission, enzyme mechanism, enzyme inactivation
- MeSH terms
- Animals, Catalysis, Cell Line, Enzyme Activation, Free Radicals, Cyclic GMP, Guanylate Cyclase, Humans, Models, Chemical, Nitric Oxide, Structure-Activity Relationship, Signal Transduction, Gene Expression, Nitric Oxide Synthase
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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