Nitric-oxide synthase: A cytochrome P450 family foster child
Abstract
Nitric-oxide synthase (NOS), the enzyme responsible for mammalian NO generation, is no cytochrome P450, but there are striking similarities between both enzymes. First and foremost, both are heme-thiolate proteins, employing the same prosthetic group to perform similar chemistry. Moreover, they share the same redox partner, a diflavoprotein reductase, which in the case of NOS is incorporated with the oxygenase in one polypeptide chain. There are, however, also conspicuous differences, such as the presence in NOS of the additional cofactor tetrahydrobiopterin, which is applied as an auxiliary electron donor to prevent decay of the oxyferrous complex to ferric heme and superoxide. In this review similarities and differences between NOS and cytochrome P450 are analyzed in an attempt to explain why NOS requires BH4 and why NO synthesis is not catalyzed by a member of the cytochrome P450 family.
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BH4 plays a critical role in the catalytic cycle of NOS.
“In addition, BH4 plays a critical role in the catalytic cycle of NOS (87, 204, 377, 904, 933, 1000, 1007).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [377]
CYPOR is a diflavin protein structurally and evolutionarily related to the reductase domain of the NOS enzymes.
“CYPOR is a diflavin protein, structurally and evolutionarily related to the reductase domain of the NOS enzymes (377) that functions as a general reductase of the many CYP proteins.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [377]
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- Authors
- Gorren, A. C. F., & Mayer, B.
- Affiliations
- University of Graz (AT)
- Corresponding author
- Gorren, Antonius C.F.
- Venue
- Biochimica et Biophysica Acta (BBA) - General Subjects
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 1770
- Issue
- 3
- Pages
- 432-445
- ISSN
- 0304-4165 (ISSN-L)
- OpenAlex
- W2044259132
- Cited by
- 129
- References
- 134
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 4 · 2013: 13 · 2012: 4
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- nitric oxide synthase, cytochrome P450, tetrahydrobiopterin, flavoprotein reductase, oxygenase, superoxide, electron transfer, enzyme evolution, nitric oxide production
- MeSH terms
- Animals, Bacterial Proteins, Biological Transport, Cytochrome P-450 Enzyme System, Humans, Nitric Oxide, Oxidation-Reduction, Protons, Nitric Oxide Synthase
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