Journal of Inherited Metabolic Disease

, Volume 18, Issue 6, pp 653-664

First online:

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

  • G. M. KnudsenAffiliated withDepartment of Neurology, University Hospital Rigshospitalet
  • , S. HasselbalchAffiliated withDepartment of Neurology, University Hospital Rigshospitalet
  • , P. B. ToftAffiliated withKennedy Institute
  • , E. ChristensenAffiliated withSection of Clinical Genetics, Department of Pediatrics, University Hospital Rigshospitalet
  • , O. B. PaulsonAffiliated withDepartment of Neurology, University Hospital Rigshospitalet
  • , H. LouAffiliated withKennedy Institute

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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.