Kinetics of phenylalanine transport at the human blood-brain barrier investigated in vivo.

[classical phenylketonuria]

In vivo proton magnetic resonance spectroscopy was used to investigate intracerebral phenylalanine (Phe ) concentrations in nine patients with classical phenylketonuria (PKU ). The study included serial examinations (n = 31 ; plasma Phe levels : 0 .47 -2 .24 mmol /l ) of patients either receiving a Phe-restricted diet (200 mg Phe per day ; four patients ) or a diet rich in Phe (1000 mg Phe per day ; three patients ). No spectrum showed metabolic abnormalities besides elevated Phe . Difference spectroscopy yielded intracerebral Phe concentrations between 0 .20 and 0 .76 mmol /l . Regional variations between parieto-occipital periventricular brain , frontal brain , and cerebellum were not statistically significant . Data could be fitted assuming saturable Phe transport into the brain , based on a symmetric Michaelis-Menten model (characterized by an apparent Michaelis transport constant , K (t ,app ), and a maximum transport velocity , Tmax ) and constant Phe consumption in the brain cells (described by a velocity Vmax ). Non-linear least-squares fitting of the combined data from all patients yielded K (t ,app ) = 0 .16 +/- 0 .11 mmol /l and (Tmax / Vmax ) = 9 .0 +/- 4 .1 . Carrier saturation and competitive inhibition of the influx of other large neutral amino acids can be expected at plasma Phe levels usually found in PKU patients .