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

N Sakai, K Saito, S Kaufman, M P Heyes, S Milstien
Biochemical Journal Oct 15, 1993, 295 (2) 543-547; DOI: 10.1042/bj2950543
N Sakai
*Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, MD 20892, U.S.A.
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K Saito
†Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892, U.S.A.
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S Kaufman
*Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, MD 20892, U.S.A.
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M P Heyes
†Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892, U.S.A.
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S Milstien
*Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, MD 20892, U.S.A.
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Abstract

Activation of the immune system which occurs in inflammatory disease 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-gamma 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 sepia-pterin 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.

  • © 1993 The Biochemical Society, London
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October 1993

Volume: 295 Issue: 2

Biochemical Journal: 295 (2)
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Induction of pterin synthesis is not required for cytokine-stimulated tryptophan metabolism
N Sakai, K Saito, S Kaufman, M P Heyes, S Milstien
Biochemical Journal Oct 1993, 295 (2) 543-547; DOI: 10.1042/bj2950543
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Induction of pterin synthesis is not required for cytokine-stimulated tryptophan metabolism
N Sakai, K Saito, S Kaufman, M P Heyes, S Milstien
Biochemical Journal Oct 1993, 295 (2) 543-547; DOI: 10.1042/bj2950543

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