Tetrahydrobiopterin, superoxide, and vascular dysfunction

Vásquez-Vivar, Jeannette

doi:10.1016/j.freeradbiomed.2009.07.024

Cited by 84Nitric Oxide and Endothelin EffectsFolate and B Vitamins ResearchMetabolism and Genetic Disorders

Tetrahydrobiopterin, superoxide, and vascular dysfunction

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Vásquez-Vivar, Jeannette·2009·Free Radical Biology and Medicine

DOI 10.1016/j.freeradbiomed.2009.07.024PMC PMC2852262

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Abstract

(6R)-5,6,7,8-Tetrahydrobiopterin (BH(4)) is an endogenously produced pterin that is found widely distributed in mammalian tissues. BH(4) works as a cofactor of aromatic amino acid hydroxylases and nitric oxide synthases. In the vasculature a deficit of BH(4) is implicated in the mechanisms of several diseases including atherosclerosis, hypertension, diabetic vascular disease, and vascular complications from cigarette smoking and environmental pollution. These ill-effects are connected to the ability of BH(4) to regulate reactive oxygen species levels in the endothelium. The possibility of using BH(4) as a therapeutical agent in cardiovascular medicine is becoming more compelling and many biochemical and physiological aspects involved in this application are currently under investigation. This review summarizes our current understanding of BH(4) reactivity and some aspects of cellular production and regulation.

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All NOS isoforms contain the cofactor tetrahydrobiopterin THB, and in its absence NOS produces superoxide •O2− instead of •NO.
“All NOS isoforms contain the important cofactor tetrahydrobiopterin THB, and in its absence, NOS produces superoxide •O2− instead of •NO [107].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [107]

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Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
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Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS
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Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin
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Maintenance of cellular tetrahydrobiopterin homeostasis
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Neuronal vulnerability to fetal hypoxia-reoxygenation injury and motor deficit development relies on regional brain tetrahydrobiopterin levels
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Aged garlic extract restores nitric oxide bioavailability in cultured human endothelial cells even under conditions of homocysteine elevation
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Role of Arginine Guanidinium Moiety in Nitric-oxide Synthase Mechanism of Oxygen Activation
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Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite
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Mitochondria-Targeted Spin Traps: Synthesis, Superoxide Spin Trapping, and Mitochondrial Uptake
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Inorganic Polyphosphate Is Essential for Salmonella Typhimurium Virulence and Survival in Dictyostelium discoideum
Varas, M. A., Riquelme-Barrios, S., Valenzuela, C., Marcoleta, A. E., Berríos-Pastén, C., Santiviago, C. A., & Chávez, F. P. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00008 · Cited by 29 · see citing works
Differential effects of ischemia/reperfusion on endothelial function and contractility in donation after circulatory death
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Mechanism of development of depression and probiotics as adjuvant therapy for its prevention and management
Gayathri, D., & Rashmi, B. S. (2017) · Mental Health & Prevention · doi:10.1016/j.mhp.2017.01.003 · Cited by 29 · see citing works
NO Way to Relax
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Impact of SOD in eNOS uncoupling: a two-edged sword between hydrogen peroxide and peroxynitrite
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Cell type-specific recycling of tetrahydrobiopterin by dihydrofolate reductase explains differential effects of 7,8-dihydrobiopterin on endothelial nitric oxide synthase uncoupling
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Oxidative Stress and Cell Death in Cardiovascular Disease
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Decreased Expression and Uncoupling of Endothelial Nitric Oxide Synthase in the Cerebral Cortex of Rats with Thioacetamide-Induced Acute Liver Failure
Milewski, K., Czarnecka, A. M., Albrecht, J., & Zielińska, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136662 · Cited by 23 · see citing works
Possible involvement of tetrahydrobiopterin in the disturbance of redox homeostasis in sepsis – Induced brain dysfunction
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Insights into Molecular Structure of Pterins Suitable for Biomedical Applications
Buglak, A. A., Kapitonova, M. A., Vechtomova, Y. L., & Telegina, T. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315222 · Cited by 23 · see citing works
Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human melanoma development
Gonçalves, D. A., de Sousa, R. X., Gonçalves, J. D., Silva, D. B., Soares, J. P. M., Icimoto, M. Y., Correa, C. S. A., Gimenez, M., Angelis, K. D., Llesuy, S., et al. (2019) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2019.105592 · Cited by 21 · see citing works
Tetrahydrobiopterin Protects Soluble Guanylate Cyclase against Oxidative Inactivation
Schmidt, K., Neubauer, A., Kolesnik, B., Stasch, J., Werner, E. R., Gorren, A. C. F., & Mayer, B. (2012) · Molecular Pharmacology · doi:10.1124/mol.112.079855 · Cited by 20 · see citing works
Machine perfusion of donor heart with normothermic blood versus hypothermic HTK in preserving coronary endothelium in a porcine model of DCD
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Is tetrahydrobiopterin a therapeutic option in diabetic hypertensive patients?
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Computational analysis of interactions of oxidative stress and tetrahydrobiopterin reveals instability in eNOS coupling
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How does ascorbate improve endothelial dysfunction? - A computational analysis
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Authors: Vásquez-Vivar, J.
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2009-10
Volume: 47
Issue: 8
Pages: 1108-1119
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/j.freeradbiomed.2009.07.024
PMC: PMC2852262
OpenAlex: W1968689753
Cited by: 84
References: 108
Citations by year: 2026: 3 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 7 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 12 · 2012: 6
FWCI: 0.95
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Free Radical Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL067244, HL067244)
National Institute of Neurological Disorders and Stroke (NS054017, R21NS054017)
Topics: Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords: tetrahydrobiopterin, superoxide, vascular dysfunction, nitric oxide synthase, aromatic amino acid hydroxylases, reactive oxygen species, endothelium, atherosclerosis, hypertension, diabetic vascular disease, cigarette smoking, environmental pollution, BH4 deficiency, BH4 supplementation, cardiovascular therapeutics
MeSH terms: Biopterins, Cardiovascular Diseases, Humans, Superoxides, Vasodilation

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Tetrahydrobiopterin, superoxide, and vascular dysfunction

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