In vivo studies of the tryptophan-5-hydroxylase system

An in vivo determination of tryptophan-5-hydroxylase (E.C. 1.14.16.4) activity is described. Subjects were loaded with deuterated L-tryptophan-d5 (50 mg/kg body weight) and the deuterated serotonin-d4 in urine was analysed using mass fragmentography. Four control subjects were dosed orally and two of them also intravenously with 50 mg/kg of L-tryptophan-d5. One patient with atypical phenylketonuria (PKU) due to a tetrahydrobiopterin (BH4) deficiency was dosed without and during BH4 treatment. Without BH4, the patient showed only minor formation of deuterated serotonin. After BH4 administration (2.5 mg/kg body weight) the serotonin formation increased about four-fold but was not normalized. Serotonin in urine and blood was analyzed as the pentafluoropropionyl (PFP) derivative using gas chromatography—mass fragmentography. Deuterated serotonin was used as internal standard. The analysis of tryptamine can be performed with the same procedure.