Journal of Inherited Metabolic Disease

, Volume 18, Issue 6, pp 653–664

Blood-brain barrier transport of amino acids in healthy controls and in patients with phenylketonuria


  • G. M. Knudsen
    • Department of NeurologyUniversity Hospital Rigshospitalet
  • S. Hasselbalch
    • Department of NeurologyUniversity Hospital Rigshospitalet
  • P. B. Toft
    • Kennedy Institute
  • E. Christensen
    • Section of Clinical Genetics, Department of PediatricsUniversity Hospital Rigshospitalet
  • O. B. Paulson
    • Department of NeurologyUniversity Hospital Rigshospitalet
  • H. Lou
    • Kennedy Institute

DOI: 10.1007/BF02436753

Cite this article as:
Knudsen, G.M., Hasselbalch, S., Toft, P.B. et al. J Inherit Metab Dis (1995) 18: 653. doi:10.1007/BF02436753


Blood-brain barrier permeability to phenylalanine and leucine in four patients with phenylketonuria and in four volunteers was measured five times by the double-indicator method at increasing plasma concentrations of phenylalanine. Based on the permeability-surface area product (PS) from blood to brain (PS1) and on plasma phenylalanine levels, Vmax and the apparentKm for phenylalanine were determined.

Statistically significant relationships between plasma phenylalanine and PS1 were established in three out of four volunteers, the averageVmax value being 46.7 nmol/g per min and the apparentKm 0.328 mmol/L. Owing to saturation of the carrier, such a relationship could not be established in the patients.

In phenylketonuria, PS1 for phenylalanine and leucine decreased significantly by 55% and 46%, respectively. Transport from brain back to blood, PS2, decreased significantly and cerebral large neutral amino acid net uptake was generally decreased in patients with phenylketonuria.

In conclusion, the transport ofl-phenylalanine across the human blood-brain barrier follows Michaelis-Menten kinetics. In phenylketonuria, brain permeability to large neutral amino acids is reduced by about 50% and net uptake appears decreased.

Copyright information

© Society for the Study of Inborn Errors of Metabolism and Kluwer Academic Publishers 1995