Serotonin and dopamine synthesis in phenylketonuria

Two regulation systems of the serotonin and dopamine biosynthesis in patients with classical and atypical PKU were investigated. In classical PKU, the serotonin and dopamine biosynthesis is inhibited by high L-phenylalanine in blood and tissues. The dopamine formation in vivo was inhibited by phenylalanine blood concentrations higher than 25 mg/dl: the serotonin formation was inhibited even at a phenylalanine blood concentration of only 8 mg/dl. In two patients with dihydrobiopterin synthetase deficiency, the dopamine, and even more pronounced the serotonin, excretions are considerably reduced. The dopamine excretion was reduced to about 50% and the serotonin excretion to only 10% compared to controls. Under BH4 therapy (16 mg daily), the dopamine values increased about twice, serotonin threefold and the phenylalanine blood concentration normalized to 1-1.5 mg/dl. On loading a patient with BH2 synthetase deficiency with 50 mg/kg deuterated tryptophan-d5 and 150 mg/kg deuterated tyrosine d2 (phenylalanine blood concentration of 16 mg/dl), deuterated dopamine d1 and serotonin d4 could only be formed in detectable amounts after BH4 administration. During BH4 therapy the amount of dopamine d1 and serotonin d4 formed was lower than but comparable to normal controls.