GTP cyclohydrolase I is coinduced in hepatocytes stimulated to produce nitric oxide

David A. Geller, Mauricio Di Silvio, Timothy R. Billiar, Kazuyuki Hatakeyama*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


GTP cyclohydrolase I is the rate-controlling enzyme in the production of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase. Here we show that GTP cyclohydrolase I mRNA was present in unstimulated hepatocytes and was up-regulated 2- to 3-fold concurrently with iNOS induction induced in vivo by LPS injection and in vitro by stimulation with LPS and inflammatory cytokines tumor necrosis factor α, interleukin-1 β, and interferon-γ. Hepatocyte GTP cyclohydrolase I enzyme activity increased 2-fold in vivo after LPS. This coinduction of GTP cyclohydrolase I resulted in increased total intracellular biopterin which supported induced NO synthesis. The addition of a GTP cyclohydrolase I inhibitor to the stimulated hepatocytes decreased intracellular biopterin levels and resulted in a decrease in NO production. The results show that GTP cyclohydrolase I is up-regulated by certain acute inflammatory conditions. Further, the results indicate that biopterin is essential as a cofactor for induced NO synthase activity in hepatocytes. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)633-641
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - 24 Sep 2000
Externally publishedYes


  • Acute inflammation
  • Biopterin
  • Endotoxin
  • GTP cyclohydrolase I
  • Hepatocyte
  • Liver
  • Nitric oxide
  • Nitric oxide synthase
  • Tetrahydrobiopterin


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