Figure 2.

Effect of immune activation on the availability of tetrahydrobiopterin (BH4). The guanosine-triphosphate-cyclohydrolase-1 (GTP-CH1) is the rate limiting enzyme of guanosine-triphosphate (GTP) conversion in dihydrobiopterin (BH2). Increased GTP-CH1 activity occurring in conditions of immune activation ultimately leads to the production of neopterin at the expense of tetrahydrobiopterin (BH4) formation. BH4 plays a fundamental role in neurotransmitter synthesis, in particular serotonin and dopamine, by acting as a cofactor of the tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH). Cytokine-induced GTP-CH1 activation reduces therefore monoaminergic neurotransmission. BH4 is also a cofactor of the nitric oxide synthase (NOS). Reduced BH4 availability can indirectly contributes to increase the production of free radicals promoting oxidative stress.