Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine 2,3-dioxygenase activity in human cells and cell lines by interferon-gamma.
In all of eight tested human cells and cell lines with inducible indoleamine 2,3-dioxygenase (EC 1.13.11.17) tetrahydrobiopterin biosynthesis was activated by interferon-gamma. This was demonstrated by GTP cyclohydrolase I (EC 3.5.4.16) activities and intracellular neopterin and biopterin concentrations. Pteridine synthesis was influenced by extracellular tryptophan. In T 24-cell extracts, submillimolar concentrations of tetrahydrobiopterin stimulated the indoleamine 2,3-dioxygenase reaction.
Werner
E R
ER
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Werner-Felmayer
G
G
Fuchs
D
D
Hausen
A
A
Reibnegger
G
G
Wachter
H
H
D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis; D003067:Coenzymes / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006136:GTP Cyclohydrolase / Q000378:metabolism; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D019798:Neopterin; D014364:Tryptophan / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D003067:Coenzymes; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D006136:GTP Cyclohydrolase; C003402:sapropterin