Induction of pterin synthesis is not required for cytokine-stimulated tryptophan metabolism

N. Sakai, Kuniaki Saito, S. Kaufman, M. P. Heyes, S. Milstien

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Activation of the immune system which occurs in inflammatory diseases leads to parallel increases in pterin synthesis and increased production of neuroactive L-tryptophan metabolites. Several model systems were studied to determine whether pterins, which are cofactors for hydroxylation reactions, could be required in the oxidative kynurenine pathway of L-tryptophan degradation. Treatment of mice with interferon-γ increased L-tryptophan metabolism without any corresponding change in tissue biopterin concentrations. Cytokine-treated human fibroblasts, macrophages and glioblastoma cells all showed increases in kynurenine production, which were completely independent of pterin synthesis. When pterin synthesis de novo was blocked, either by an inhibitor of GTP cyclohydrolase or because of a genetic deficiency of one of the enzymes of the pathway of pterin biosynthesis, cytokine-stimulated increases in tryptophan metabolism were unaffected. Furthermore, increasing intracellular tetrahydrobiopterin concentrations by treating cells with sepiapterin also had no effect on markers of tryptophan metabolism. Therefore, both normal and cytokine-stimulated L-tryptophan metabolism appears to be completely independent of pterin biosynthesis.

Original languageEnglish
Pages (from-to)543-547
Number of pages5
JournalBiochemical Journal
Volume295
Issue number2
DOIs
Publication statusPublished - 01-01-1993
Externally publishedYes

Fingerprint

Pterins
Metabolism
Tryptophan
Cytokines
Kynurenine
Biosynthesis
GTP Cyclohydrolase
Biopterin
Hydroxylation
Macrophages
Immune system
Fibroblasts
Glioblastoma
Metabolites
Interferons
Immune System
Chemical activation
Tissue
Degradation
Enzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sakai, N. ; Saito, Kuniaki ; Kaufman, S. ; Heyes, M. P. ; Milstien, S. / Induction of pterin synthesis is not required for cytokine-stimulated tryptophan metabolism. In: Biochemical Journal. 1993 ; Vol. 295, No. 2. pp. 543-547.
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Induction of pterin synthesis is not required for cytokine-stimulated tryptophan metabolism. / Sakai, N.; Saito, Kuniaki; Kaufman, S.; Heyes, M. P.; Milstien, S.

In: Biochemical Journal, Vol. 295, No. 2, 01.01.1993, p. 543-547.

Research output: Contribution to journalArticle

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