The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria
Open accessAbstract
Large neutral amino acids (LNAAs), including phenylalanine (Phe), compete for transport across the blood-brain barrier (BBB) via the L-type amino acid carrier. Accordingly, elevated plasma Phe impairs brain uptake of other LNAAs in patients with phenylketonuria (PKU). Direct effects of elevated brain Phe and depleted LNAAs are probably major causes for disturbed brain development and function in PKU. Competition for the carrier might conversely be put to use to lower Phe influx when the plasma concentrations of all other LNAAs are increased. This hypothesis was tested by measuring brain Phe in patients with PKU by quantitative 1H magnetic resonance spectroscopy during an oral Phe challenge with and without additional supplementation with all other LNAAs. Baseline plasma Phe was approximately 1,000 micromol/l and brain Phe was approximately 250 micromol/l in both series. Without LNAA supplementation, brain Phe increased to approximately 400 micromol/l after the oral Phe load. Electroencephalogram (EEG) spectral analysis revealed acutely disturbed brain activity. With concurrent LNAA supplementation, Phe influx was completely blocked and there was no slowing of EEG activity. These results are relevant for further characterization of the LNAA carrier and of the pathophysiology underlying brain dysfunction in PKU and for treatment of patients with PKU, as brain function might be improved by continued LNAA supplementation.
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Cited by
Branched-Chain Amino Acids and Brain Function
Fernstrom, J. D. (2005) · The Journal of Nutrition · doi:10.1093/jn/135.6.1539s · Cited by 514
Wiersema, J. R., van der Meere, J. J., & Roeyers, H. (2005) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-005-0110-1 · Cited by 37
Metabolism of carnitine in phenylacetic acid-treated rats and in patients with phenylketonuria
Fischer, G. M., Nemeti, B., Farkas, V., Debreceni, B., Laszlo, A., Schaffer, Z., Somogyi, C., & Sandor, A. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00023-5 · Cited by 20
Metadata
- Authors
- Pietz, J., Kreis, R., Rupp, A., Mayatepek, E., Rating, D., Boesch, C., & Bremer, H. J.
- Venue
- Journal of Clinical Investigation
- Published
- 1999-04-15
- Volume
- 103
- Issue
- 8
- Pages
- 1169-1178
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2052438797
- Cited by
- 300
- References
- 33
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Pietz, J., Kreis, R., Rupp, A., Mayatepek, E., Rating, D., Boesch, C., & Bremer, H. J. (1999). Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria. Journal of Clinical Investigation. https://doi.org/10.1172/jci5017
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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