Journal of Inherited Metabolic Disease

, Volume 12, Issue 2, pp 166–180 | Cite as

Evidence for inhibition of exodus of small neutral amino acids from non-brain tissues in hyperphenylalaninaemic rats

  • C. de Cespedes
  • J. G. Thoene
  • K. Lowler
  • H. N. Christensen


The mechanism of the depletion of several plasma amino acids in PKU has remained unexplained. In the present study, a statistically significant decrease in the plasma concentration of several amino acids was observed 2 h after the intraperitoneal injection of Phe to weanling rats. The pattern was very similar to the one observed in PKU patients. Statistically significant increases in the distribution ratios liver/plasma and, mainly, muscle/plasma ratios accompanied in most of the cases the corresponding decreases in plasma concentrations. Equimolar injection under the same conditions of the non-insulinogenic transport system L analogue, the a(±) isomer of the 2-amino-norbornane-2-carboxylic acid, produced, in a parallel effect to Phe, statistically significant increases in the distribution ratios of Ala and Gly, and probably of Pro in muscle, as well as of Ala in liver. These results seem to indicate that the high intracellular Phe attained inhibits the exodus of small neutral amino acids through system L, causing their depletion in plasma and ultimately in the brain. This effect may be additive to the inhibition by Phe of the entry of bulky neutral amino acids at the level of the blood-brain barrier. Further study is needed to assess the relevance of these effects to PKU.


Public Health Internal Medicine Plasma Concentration Metabolic Disease Transport System 
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Copyright information

© SSIEM and Kluwer Academic Publishers 1989

Authors and Affiliations

  • C. de Cespedes
    • 1
  • J. G. Thoene
    • 1
  • K. Lowler
    • 1
  • H. N. Christensen
    • 1
  1. 1.Departments of Biological Chemistry and PediatricsUniversity of Michigan Medical SchoolAnn ArborUSA

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