PMID- 15509890
OWN - NLM
STAT- MEDLINE
DCOM- 20090128
LR  - 20231213
IS  - 1559-0283 (Electronic)
IS  - 1085-9195 (Linking)
VI  - 41
IP  - 3
DP  - 2004
TI  - Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial 
      cells.
PG  - 415-34
AB  - 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.
FAU - Shi, Wenjuan
AU  - Shi W
AD  - Faculty of Nutrition and Department of Animal Science, Texas A&M University, 
      College Station, TX 77843, USA.
FAU - Meininger, Cynthia J
AU  - Meininger CJ
FAU - Haynes, Tony E
AU  - Haynes TE
FAU - Hatakeyama, Kazuyuki
AU  - Hatakeyama K
FAU - Wu, Guoyao
AU  - Wu G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Cell Biochem Biophys
JT  - Cell biochemistry and biophysics
JID - 9701934
RN  - 0 (Cytokines)
RN  - 0 (Estrogens)
RN  - 0 (Glucocorticoids)
RN  - 0 (Biopterins)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - 6779-87-9 (7,8-dihydrobiopterin)
RN  - EC 3.5.4.16 (GTP Cyclohydrolase)
RN  - EGX657432I (sapropterin)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Biopterins/*analogs & derivatives/biosynthesis/chemistry
MH  - Cytokines/metabolism
MH  - Endothelial Cells/*metabolism
MH  - Estrogens/chemistry
MH  - GTP Cyclohydrolase/metabolism
MH  - *Gene Expression Regulation
MH  - Glucocorticoids/chemistry
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Models, Biological
MH  - Nitric Oxide/metabolism
MH  - Oxygen/chemistry
MH  - Phenylalanine/chemistry
RF  - 127
EDAT- 2004/10/29 09:00
MHDA- 2009/01/29 09:00
CRDT- 2004/10/29 09:00
PHST- 2004/10/29 09:00 [pubmed]
PHST- 2009/01/29 09:00 [medline]
PHST- 2004/10/29 09:00 [entrez]
AID - CBB:41:3:415 [pii]
AID - 10.1385/CBB:41:3:415 [doi]
PST - ppublish
SO  - Cell Biochem Biophys. 2004;41(3):415-34. doi: 10.1385/CBB:41:3:415.