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

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

研究成果: Article査読

12 被引用数 (Scopus)


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.

ジャーナルBiochemical Journal
出版ステータスPublished - 1993

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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