Transport of amino acids across the blood-brain barrier: Implications for treatment of maternal phenylketonuria Maternal PKU Workshop DOI:
Cite this article as: Gardiner, R.M. J Inherit Metab Dis (1990) 13: 627. doi:10.1007/BF01799517 Summary
Amino acid transport at the mammalian blood-brain barrier has been extensively characterized. Transport of
l-phenylalanine and related neutral amino acids is known to be mediated by a stereospecific, sodium independent, saturable carrier. The affinity of this carrier is much higher than that of comparable systems in other tissues. This feature renders it susceptible to inhibition. It has been suggested that inhibition of neutral amino acid influx into the brain by hyperphenylalaninaemia contributes to the pathophysiology of brain damage in this condition.
Methods for investigation of amino acid transport at the blood-brain barrier are discussed, and current knowledge of blood-brain barrier amino acid transport at the blood-brain barrier is reviewed. Developmental changes are delineated, with particular reference to recent work on the ovine blood-brain barrier.
There is insufficient information concerning blood-brain barrier transport of amino acids in the fetal brain to allow firm conclusions to be drawn concerning implications for treatment of maternal PKU. Reasonable extrapolation from animal data suggests that transport inhibition may contribute to impaired fetal brain growth in maternal PKU, and can be minimized by attempts to maintain a normal milieu from the time of conception.
Banos, G., Daniel, P. M., Moorhouse, S. R. and Pratt, O. E. The requirements of the brain for some amino acids.
246 (1975) 539–548
Betz, A. L. and Goldstein, G. W. Polarity of the blood-brain barrier: neutral amino acid transport into isolated brain capillaries.
202 (1978) 225–227
Bradbury, M. W. B.
The Concept of a Blood-Brain Barrier
, John Wiley, Chichester and New York, 1979
Braun, L. D., Cornford, E. M. and Oldendorf, W.H. Newborn rabbit blood-brain barrier is selectively permeable and differs substantially from the adult.
34 (1980) 147–152
Brenton, D. P. and Gardiner, R. M. Transport of
-phenylalanine and related amino acids at the ovine blood-brain barrier.
402 (1988) 497–514
Christensen, H. N. On the development of amino acid transport systems.
32 (1973) 19–28
Cremer, J. E., Braun, L. D. and Oldendorf, W. H. Changes during development in transport processes of the blood-brain barrier.
Biochim. Biophys. Acta
448 (1976) 633–637
Crone, C. Facilitated transfer of glucose from blood into brain tissue.
181 (1965) 103–113
Drogani, E., Bearley, M., Smith, I. and Lloyd, J. K. Timing of strict diet in relation to fetal damage in maternal phenylketonuria.
2 (1987) 927–930
Joo, F. The blood-brain barrier
: ten years of research on microvessels isolated from the brain.
7(1) (1985) 1–25
Levy, H. L. and Waisbren, S. E. Effects of untreated maternal phenylketonuria and hyperphenylalaninaemia on the fetus.
N. Engl. J. Med.
309 (1983) 1269–1274
Momma, S., Aoyagi, M., Rapoport, S. I. and Smith, Q. R. Phenylalanine transport across the blood-brain barrier as studied with the
brain perfusion technique.
48 (1987) 1291–1300
Oldendorf, W. H. Brain uptake of radiolabelled amino acid, amines and hexoses after arterial injection.
Am. J. Physiol.
221 (1971) 1629–1639
Pardridge, W. M. and Mietus, L. J. Kinetics of neutral amino acid transport through the blood-brain barrier of the newborn rabbit.
38 (1982) 955–962
Pratt, O. E. The transport of metabolisable substances into the living brain.
Adv. Exp. Med. Biol.
69 (1976) 55–75
Pratt, O. E. Transport inhibition in the pathology of phenylketonuria and other inherited metabolic diseases.
J. Inher. Metab. Dis.
5 Suppl. 2 (1982) 75–81
Sarna, G. S., Kantamareni, B. D. and Curzon, G. Variables influencing the effect of a meal on brain tryptophan.
44 (1985) 1575–1580
Sershen, H. and Lajtha, A. Capillary transport of amino acids in the developing brain.
53 (1976) 465–474
Seta, K., Sershen, H. and Lajtha, A. Cerebral amino acid uptake
in newborn mice.
47 (1972) 415–425
Smith, Q. R., Momma, S., Aoyagi, M. and Rapoport, S. I. Kinetics of neutral amino acid transport across the blood-brain barrier.
49 (1987) 1651–1658
Takasato, Y., Rapoport, S. I. and Smith, Q. R. An
brain perfusion technique to study cerebrovascular transport in rat.
Am. J. Physiol.
247 (1984) H484-H493
Yudilevich, D. L., De Rose, N. and Sepulveda, F. V. Facilitated transport of amino acids through the blood brain barrier of the dog. Studies in a single capillary circulation.
44 (1972) 569–578
Yudilevich, D. L., Wheeler, C. P. D. and Bustamante, J. C. A comparative view of amino acid transport across the blood-brain barrier (endothelium) and the placenta (trophoblast). In:
Proceedings of Symposium on Peptide and Amino Acid Transport Mechanisms in the Central Nervous System, (In press) Copyright information
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