Document Detail

Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial cells.
MedLine Citation:
PMID:  15509890     Owner:  NLM     Status:  MEDLINE    
Tetrahydrobiopterin (BH4) is a member of the pterin family that has a core structure of pyrazino-2,3-d-pyrimidine rings. Because BH4 is an essential cofactor for the biosynthesis of nitric oxide (a major vasodilator), there is growing interest in BH4 biochemistry in endothelial cells (the cells that line blood vessels). BH4 is synthesized via de novo and salvage pathways from guanosine 5'-triphosphate (GTP) and 7,8-dihydrobiopterin, respectively, in animal cells. GTP cyclohydrolase-I (GTP-CH) is the first and rate-controlling enzyme in the de novo pathway. Available evidence shows that endothelial GTP-CH expression and BH4 synthesis are stimulated by a wide array of nutritional (phenylalanine and arginine), hormonal (insulin and estrogen), immunological (inflammatory cytokines including interleukin [IL]-1, interferon-gamma, and tumor necrosis factor-alpha), therapeutic (statins and cyclosporin A), and endothelium-derived (basic fibroblast growth factor and H2O2) factors. In contrast, glucocorticoids and anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor [TGF]-beta) inhibit endothelial BH4 synthesis. Because BH4 is oxidized to 7,8-dihydrobiopterin and 7,8-dihydropterin at physiological pH, endothelial BH4 homeostasis is regulated by both BH4 synthesis and its oxidation. Vitamin C, folate, and other antioxidants enhance endothelial BH4 bioavailability through chemical stabilization or scavenging of reactive oxygen species, thereby contributing to the maintenance of physiological homeostasis in the endothelium. New knowledge about the cellular and molecular mechanisms for the regulation of endothelial BH4 synthesis and bioavailability is beneficial for developing effective means to prevent and treat cardiovascular disorders, the leading cause of death in developed nations.
Wenjuan Shi; Cynthia J Meininger; Tony E Haynes; Kazuyuki Hatakeyama; Guoyao Wu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Cell biochemistry and biophysics     Volume:  41     ISSN:  1559-0283     ISO Abbreviation:  Cell Biochem. Biophys.     Publication Date:  2004  
Date Detail:
Created Date:  2004-10-28     Completed Date:  2009-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9701934     Medline TA:  Cell Biochem Biophys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  415-34     Citation Subset:  IM    
Faculty of Nutrition and Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.
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MeSH Terms
Biopterin / analogs & derivatives*,  biosynthesis,  chemistry
Cytokines / metabolism
Endothelial Cells / metabolism*
Estrogens / chemistry
GTP Cyclohydrolase / metabolism
Gene Expression Regulation*
Glucocorticoids / chemistry
Hydrogen-Ion Concentration
Models, Biological
Nitric Oxide / metabolism
Oxygen / chemistry
Phenylalanine / chemistry
Reg. No./Substance:
0/Cytokines; 0/Estrogens; 0/Glucocorticoids; 10102-43-9/Nitric Oxide; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; 63-91-2/Phenylalanine; 6779-87-9/7,8-dihydrobiopterin; 7782-44-7/Oxygen; EC Cyclohydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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