Blood-brain barrier transport of amino acids in healthy controls and in patients with phenylketonuria
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Blood-brain barrier transport of amino acids in healthy controls and in patients with phenylketonuria. / Knudsen, G M; Hasselbalch, S; Toft, P B; Christensen, E; Paulson, O B; Lou, H.
In: Journal of Inherited Metabolic Disease, Vol. 18, No. 6, 1995, p. 653-64.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Blood-brain barrier transport of amino acids in healthy controls and in patients with phenylketonuria
AU - Knudsen, G M
AU - Hasselbalch, S
AU - Toft, P B
AU - Christensen, E
AU - Paulson, O B
AU - Lou, H
PY - 1995
Y1 - 1995
N2 - 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 apparent Km for phenylalanine were determined. Statistically significant relationships between plasma phenylalanine and PS1 were established in three out of four volunteers, the average Vmax value being 46.7 nmol/g per min and the apparent Km 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 of L-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.
AB - 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 apparent Km for phenylalanine were determined. Statistically significant relationships between plasma phenylalanine and PS1 were established in three out of four volunteers, the average Vmax value being 46.7 nmol/g per min and the apparent Km 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 of L-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.
KW - Adult
KW - Amino Acids/metabolism
KW - Biological Transport
KW - Blood-Brain Barrier
KW - Brain/metabolism
KW - Humans
KW - Leucine/metabolism
KW - Male
KW - Phenylalanine/metabolism
KW - Phenylketonurias/metabolism
U2 - 10.1007/BF02436753
DO - 10.1007/BF02436753
M3 - Journal article
C2 - 8750601
VL - 18
SP - 653
EP - 664
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
SN - 0141-8955
IS - 6
ER -
ID: 275018230