Journal of Inherited Metabolic Disease

, Volume 18, Issue 6, pp 653–664 | Cite as

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

  • G. M. Knudsen
  • S. Hasselbalch
  • P. B. Toft
  • E. Christensen
  • O. B. Paulson
  • H. Lou
Article

Summary

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 apparentK m for phenylalanine were determined.

Statistically significant relationships between plasma phenylalanine and PS1 were established in three out of four volunteers, the averageV max value being 46.7 nmol/g per min and the apparentK m 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.

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Copyright information

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

Authors and Affiliations

  • G. M. Knudsen
    • 1
  • S. Hasselbalch
    • 1
  • P. B. Toft
    • 2
  • E. Christensen
    • 3
  • O. B. Paulson
    • 1
  • H. Lou
    • 2
  1. 1.Department of NeurologyUniversity Hospital RigshospitaletCopenhagenDenmark
  2. 2.Kennedy InstituteGlostrupDenmark
  3. 3.Section of Clinical Genetics, Department of PediatricsUniversity Hospital RigshospitaletCopenhagenDenmark

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