Abstract
Phenylalanine is accumulated in the genetically linked deficiency phenylketonuria. The effect ofl-phenylalanine on the transport of tryptophan was studied using membrane vesicles from rat-brain synaptosomes. Phenylalanine at similar concentrations to those found in phenylketonuric patients competitively inhibits tryptophan uptake, with aK i of the same order as theK m for tryptophan. This inhibition could be responsible for the depletion of serotonin found in phenylketonuria.
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Aragon, M. C., Gimenez, C., Mayor, Jr. F., Marvizon, J. G. and Valdivieso, F. Tyrosine transport by membrane vesicles isolated from rat brain.Biochim. Biophys. Acta 646 (1981) 465–470
Aragón, M. C., Gimenez, C. and Valdivieso, F. Inhibition by phenylalanine of tyrosine transport by synaptosomal plasma membrane vesicles: implications in the pathogenesis of phenylketonuria.J. Neurochem. 39 (1982) 1185–1187
Barbosa, E., Joanny, P. and Carriol, J. Accumulation active du tryptophane dans le cortex cérébral isolé du rat.C. R. Soc. Biol. (París) 164 (1970) 345–350
Blasberg, R. G. and Lajtha, A. Substrate specificity on steady-state amino acid transport in mouse brain slices.Arch. Biochem. 112 (1965) 361–377
Blau, K. Phenylalanine hydroxylase deficiency: Biochemical, physiological, and clinical aspects of phenylketonuria and related phenylalaninemias. In Youdim, M. B. H. (ed)Aromatic Amino Acid Hydroxylases and Mental Disease, Wiley, New York, NY (1979), pp. 77–139
Fernston, J. W. and Wurtzman, R. J. Brain serotonin content: physiological dependence on plasma tryptophan levels.Science 173 (1974) 149–152
Grahame-Smith, D. G. and Parfitt, A. G. Tryptophan transport across the synaptosomal membrane.J. Neurochem. 17 (1970) 1339–1352
Grahame-Smith, D. G. Studies in vivo on the relationship between brain tryptophan, brain 5-HT synthesis, and hyperactivity in rats treated with a monoamine oxidative inhibitor andl-tryptophan.J. Neurochem. 18 (1971) 1053–1066
Guroff, G. and Udenfriend, S. Studies on aromatic amino acid uptake by rat brainin vivo.J. Biol. Chem. 237 (1962) 803–806
Hedqvist, P. and Stjarne, L. The relative role of recapture and of ‘de novo’ synthesis for the maintenance of neurotransmitter homeostasis in noradrenergic nerves.Acta Physiol. Scand. 76 (1969) 270–276
Johnston, G. A. R. and Iversen, L. L. Glycine uptake in rat central nervous systems slices and homogenates: Evidence for different uptake systems in spinal cord and cerebral cortex.J. Neurochem. 18 (1971) 1951–1961
Kanner, B. I. Active transport of α-aminobutyric acid by membrane vesicles isolated from rat brain.Biochemistry 17 (1978) 1207–1211
Kanner, B. I. and Sharon, I. Active transport ofl-proline by membrane vesicles isolated from rat brain.Biochim. Biophys. Acta 600 (1980) 185–194
Korpi, E. R. Tryptophan and phenylalanine transport in rat cerebral cortex slices as influenced by sodium ions.Neurochem. Res. 5 (1980) 415–431
Kuhar, M. J. and Zarbin, M. A. Synaptosomal transport: A chloride dependence for choline, GABA, glycine, and several other compounds.J. Neurochem. 31 (1978) 251–256
Laakso, M. L. and Oja, S. S. Transport of tryptophan and tyrosine in rat brain slices in the presence of lithium.Neurochem. Res. 4 (1979) 411–423
Lädhesmäki, P. and Hannus, M.-L. Effect of aromatic acids on the influx of aromatic amino acids in rat brain slices.Exp. Brain. Res. 30 (1977) 539–548
Lajtha, A. Amino acid transport in the brainin vivo andin vitro. In Wolstenholme, G. E. W. and Fitzsimons, D. W. (eds.)Aromatic Amino Acids in the Brain, Elsevier, Amsterdam, 1974, pp. 25–41
Logan, W. J. and Snyder, S. H. High affinity uptake systems for glycine, glutamic and aspartic acids in synaptosomes of rat central nervous tissues.Brain. Res. 42 (1972) 413–431
Mandell, A. J. and Knapp, S. Regulation of serotonin biosynthesis in brain: role of the high affinity uptake of tryptophan into serotonergic neurons.Fed. Proc., Fed. Am. Soc. Exp. Biol. 36 (1977) 2142–2148
Marvizón, J. G., Mayor, Jr. F., Argón, M. C., Gimenez, C., and Valdivieso, F.l-Aspartate transport into plasma membrane vesicles derived from rat brain synaptosomes.J. Neurochem. 37 (1981) 1401–1406
Mayor, Jr. F., Marvizón, J. G., Aragon, M. C., Giménez, C. and Valdivieso, F. Glycine transport into plasma membrane vesicles derived from rat brain synaptosomes.Biochem. J. 198 (1981) 535–541
McKean, C. H., Boggs, D. E. and Peterson, N. A. The influence of high phenylalanine and tyrosine on the concentration of essential amino acids in brain.J. Neurochem. 15 (1968) 235–241
McKean, C. H. The effects of high phenylalanine concentration on serotonin and catecholamine metabolism in the human brain.Brain Res. 47 (1972) 469–476
Neame, K. D. Phenylalanine as inhibitor of transport of amino-acids in brain.Nature (London) 192 (1961) 173–174
Pratt, O. E. The transport of metabolizable substances into the living brain. In Levi, G., Battistin, L. and Lajtha, A. (eds.)Transport Phenomena in the Nervous System: Physiological and Pathological Aspects. Advances in Experimental Medicine and Biology. Plenum Press, New York, 1976, pp 55–75
Pratt, O. E. The needs of the brain for amino acids and how they are transported across the blood-brain barrier. In Belton, N. R. and Toothill, C. (eds.)Transport and Inherited Disease. MTP Press, Lancaster, 1981, pp. 87–122
Resch, K., Imm, W., Ferber, E., Wallach, D. F. M. and Fisher, H. Quantitative determination of soluble and membrane proteins through their native fluorescence.Naturwissenschaften 58 (1971) 220
Sershen, H. and Lajtha, A. Inhibition pattern of analogs indicates the presence of ten or more transport systems for amino acids in brain cells.J. Neurochem. 32 (1979) 719–726
Tyfield, L. A. and Holton, J. B. The effect of high concentrations of histidine on the level of other amino acids in plasma and brain of the mature rat.J. Neurochem. 26 (1976) 101–105
Vahvelainen, M.-L. and Oja, S. S. Kinetic analysis of phenylalanine-induced inhibition in the saturable influx of tyrosine, tryptophan, leucine and histidine into brain cortex slices from adult and 7-day-old rats.J. Neurochem. 24 (1975) 885–892
Vorhees, C. V., Butcher, R. E. and Berry, H. K. Progress in experimental phenylketonuria: a critical review.Neurosci. Biobehav. Rev. 5 (1981) 177–190
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Herrero, E., Aragon, M.C., Gimenez, C. et al. Inhibition byl-phenylalanine of tryptophan transport by synaptosomal plasma membrane vesicles: Implications in the pathogenesis of phenylketonuria. J Inherit Metab Dis 6, 32–35 (1983). https://doi.org/10.1007/BF02391190
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DOI: https://doi.org/10.1007/BF02391190