Cell Biochemistry and Biophysics

, Volume 41, Issue 3, pp 415–433

Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial cells

  • Wenjuan Shi
  • Cynthia J. Meininger
  • Tony E. Haynes
  • Kazuyuki Hatakeyama
  • Guoyao Wu
Review Article

DOI: 10.1385/CBB:41:3:415

Cite this article as:
Shi, W., Meininger, C.J., Haynes, T.E. et al. Cell Biochem Biophys (2004) 41: 415. doi:10.1385/CBB:41:3:415

Abstract

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-γ, and tumor necrosis factor-α), 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]-β) 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 know ledge 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.

Index Entries

Tetrahy drobiopterin GTP cyclohydrolase-I nitric oxide endothelial cells 

Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Wenjuan Shi
    • 1
  • Cynthia J. Meininger
    • 2
  • Tony E. Haynes
    • 1
  • Kazuyuki Hatakeyama
    • 3
  • Guoyao Wu
    • 1
    • 2
  1. 1.Faculty of Nutrition and Department of Animal ScienceTexas A&M UniversityCollege Station
  2. 2.Department of Medical Physiology and Cardiovascular Research InstituteThe Texas A&M University System Health Science CenterCollege Station
  3. 3.Department of SurgeryUniversity of PittsburghPittsburgh

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