Figure 1

Induction of neopterin formation in brain cells. Pro-inflammatory cytokines like interferon-γ (IFN-γ) induce expression of GTP-cyclohydrolase I in various brain cells. As an intermediate product 7,8-dihydroneopterin-triphosphate is produced which is further converted by pyruvoyl-tetrahydropterin synthase (PTPS) to form 5,6,7,8-tetrahydrobiopterin (BH4), the cofactor of several aromatic amino acid monooxygenases that are involved in the production of tyrosine, L-DOPA, serotonin and nitric oxide. Different from neurons, monocytic cells possess only low constitutive activity of PTPS. Thus, 7,8-dihydroneopterin-triphosphate does not undergo conversion to BH4, rather it is dephosphorylated and oxidized to neopterin in non-enzymatic reactions.