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.
- Blood-brain barrier transport of amino acids in healthy controls and in patients with phenylketonuria
Journal of Inherited Metabolic Disease
Volume 18, Issue 6 , pp 653-664
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- Kluwer Academic Publishers
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- 1. Department of Neurology, University Hospital Rigshospitalet, Copenhagen, Denmark
- 3. Kennedy Institute, Glostrup, Denmark
- 4. Section of Clinical Genetics, Department of Pediatrics, University Hospital Rigshospitalet, Copenhagen, Denmark