Abstract
Phenylalanine transport through the brain capillary wall, i.e., the blood-brain barrier (BBB), is characterized by a very high affinity (low K m ) transport system in laboratory rats. To test whether phenylalanine transport at the human BBB is also mediated by a very high affinity (low K m ) transport system, brain capillaries were isolated from fresh autopsy human brain, as well as from fresh rat brain or from fresh or 42-hour postmortem rabbit brain. The results show that the K m values for phenylalanine transport are virtually identical at either the rat or human BBB. Therefore, the marked derangements in brain amino acid metabolism caused by hyperphenylalaninemia in rats may also occur in humans at comparable increases in blood phenylalanine.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Andersen, A.E., and Avins, L. (1976). Lowering brain phenylalanine levels by giving other large neutral amino acids. Arch. Neurol. 33:686–686.
Binek-Singer, P., and Johnson, T.C. (1982). The effects of chronic hyperphenylala-ninaemia on mouse brain protein synthesis can be prevented by other amino acids. Biochem. J. 206:407–414.
Choi, T., and Pardridge, W.M. (1986). Phenylalanine transport at the human blood-brain barrier. Studies in isolated human brain capillaries. J. Biol. Chem. 261:6536–6541.
Comar, D., Saudubray, J.M., Duthilleul, A., Delforge, J., Maziere, M., Berger, G., Charpentier, C., Todd-Pokropek, A., with Crouze, M., and Depondt, E. (1981). Brain uptake of 11C-methionine in phenylketonuria. Eur. J. Pediatr. 136:13–19.
Duffy, K.R., Pardridge, W.M., and Rosenfeld, R.G. (1988). Human blood-brain barrier insulin-like growth factor (IGF) receptor. Metabolism 37:136–140.
Fernstrom, J.D., and Faller, D.V. (1978). Neutral amino acids in the brain: changes in response to food ingestion. J. Neurochem. 30:1531–1538.
Fernstrom, J.D., and Wurtman, R.J. (1972). Brain serotonin content: physiological regulation by plasma neutral amino acids. Science 178:414–416.
Frey, G.H. (1976). Use of aspartame by apparently healthy children and adolescents. J. Toxicol. Environ. Health 2:401–415.
Levy, H.L., and Waisbren, S.E. (1983). Effects of untreated maternal phenylketonuria and hyperphenylalaninemia on the fetus. N. Engl. J. Med. 309:1269–1274.
Miller, L., Braun, L.D., Pardridge, W.M., and Oldendorf, W.H. (1985). Kinetic constants for blood-brain barrier amino acid transport in conscious rats. J. Neurochem. 45:1427–1432.
Oldendorf, W.H., Sisson, W.B., and Silverstein, A. (1971). Brain uptake of sele-nomethioine Se 75. II. Reduced brain uptake of selenomethionine Se 75 in phenylketonuria. Arch. Neurol. 24:524–528.
Pardridge, W.M. (1986). Potential effects of the dipeptide sweetener aspartame on the brain. In Wurtman, R.J., and Wurtman, J.J. (eds.), Nutrition and the brain, Volume 7. New York: Raven Press, pp. 199–241.
Pardridge (1987): Phenylalanine transport at the human blood-brain barrier. In Kaufman, S. (ed.), Amino acids in health and disease: new perspectives. New York: Alan R. Liss, Inc., pp. 43–64.
Pardridge, W.M., and Choi, T. (1986). Amino acid transport at the human blood-brain barrier. Fed. Proc. 45:2073–2078.
Pardridge, W.M., and Oldendorf, W.H. (1977): Transport of metabolic substrates through the blood-brain barrier. J. Neurochem. 28:5–12.
Pardridge, W.M., Eisenbergy J., and Yang, J. (1985). Human blood-brain barrier insulin receptor. J. Neurochem. 44:1771–1778.
Pardridge, W.M., Eisenberg, J., and Yang, J. (1987). Human blood-brain barrier transferrin receptor. Metabolism 36:892–895.
Scriver, C.R., and Clow, C.L. (1980). Phenylketonuria: epitome of human biochemical genetics. N. Engl. J. Med. 303:1336–1342.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Birkhäuser Boston
About this chapter
Cite this chapter
Pardridge, W.M. (1988). Phenylalanine Transport at the Human Blood-Brain Barrier. In: Wurtman, R.J., Ritter-Walker, E. (eds) Dietary Phenylalanine and Brain Function. Birkhäuser Boston. https://doi.org/10.1007/978-1-4615-9821-3_5
Download citation
DOI: https://doi.org/10.1007/978-1-4615-9821-3_5
Publisher Name: Birkhäuser Boston
Print ISBN: 978-1-4615-9823-7
Online ISBN: 978-1-4615-9821-3
eBook Packages: Springer Book Archive