Nitric-oxide Dioxygenase Function of Human Cytoglobin with Cellular Reductants and in Rat Hepatocytes
Open accessAbstract
Cytoglobin (Cygb) was investigated for its capacity to function as a NO dioxygenase (NOD) in vitro and in hepatocytes. Ascorbate and cytochrome b(5) were found to support a high NOD activity. Cygb-NOD activity shows respective K(m) values for ascorbate, cytochrome b(5), NO, and O(2) of 0.25 mm, 0.3 microm, 40 nm, and approximately 20 microm and achieves a k(cat) of 0.5 s(-1). Ascorbate and cytochrome b(5) reduce the oxidized Cygb-NOD intermediate with apparent second order rate constants of 1000 m(-1) s(-1) and 3 x 10(6) m(-1) s(-1), respectively. In rat hepatocytes engineered to express human Cygb, Cygb-NOD activity shows a similar k(cat) of 1.2 s(-1), a K(m)(NO) of 40 nm, and a k(cat)/K(m)(NO) (k'(NOD)) value of 3 x 10(7) m(-1) s(-1), demonstrating the efficiency of catalysis. NO inhibits the activity at [NO]/[O(2)] ratios >1:500 and limits catalytic turnover. The activity is competitively inhibited by CO, is slowly inactivated by cyanide, and is distinct from the microsomal NOD activity. Cygb-NOD provides protection to the NO-sensitive aconitase. The results define the NOD function of Cygb and demonstrate roles for ascorbate and cytochrome b(5) as reductants.
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Oxygenated Cygb reacts with NO to form nitrate in a NO dioxygenation reaction that scavenges NO.
“In addition, the oxygenated form of Cygb reacts with NO to form nitrate in a NO dioxygenation reaction that scavenges NO (339) (Eq. 8)”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [339]
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References 65 · Cited by 94
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- Authors
- Gardner, A. M., Cook, M. R., & Gardner, P. R.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- University of Dayton (US)
- Corresponding author
- Gardner, Paul R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 285
- Issue
- 31
- Pages
- 23850-23857
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2911317
- OpenAlex
- W2078025686
- Cited by
- 94
- References
- 65
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 8 · 2019: 4 · 2018: 8 · 2017: 12 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 7
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association (9730193 N)
- National Institutes of Health (9730193N)
- National Institute of General Medical Sciences (R01GM065090, GM-65090)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- nitric oxide dioxygenase, nitric oxide, vitamin C, cytochrome b5, rat hepatocytes, enzyme kinetics
- MeSH terms
- Neuroglobin, Cytoglobin, Animals, Ascorbic Acid, Catalysis, Globins, Heme, Humans, Kinetics, Nerve Tissue Proteins, Nitric Oxide, Oxygenases, Cytochromes b5, Caco-2 Cells, Hepatocytes, Cell Line, Tumor, Rats
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