Reduction of serum phenylalanine levels in PKU rats with intestinal absorption inhibitors of phenylalanine (PHE): 61 View Full Text


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Article Info

DATE

1980-02

AUTHORS

J L Dhondt, J P Farriaux, M Dautrevaux, P Ardouin, L Corbeel

ABSTRACT

It has been often suggested that inhibition of the intestinal absorption of PHE would be a new approach for PKU treatment. We have previously shown that a PKU model for dietetic studies is obtained by means of the synergistic inhibition of Phenylalanine-Hydroxylase with p-chlorophenylalanine + cotrimoxazole (daily intraperitoneal injection of the 2 inhibitors leads to hyperphenylalaninemia without need for a phenylalanine load). Addition of beta-2-thienylalanine (THI) or phenylalaninol (PHE-ol) to the diet (1g%) significantly reduced phenylalaninemia: PHE: 1.30 ± 0.30, + THI : 0.70 ± 0.27, + PHE-ol:0.87 + 0.29 mmol/l. However, the effectiveness of THI or PHE-ol was mainly dependent on diet quality: with 5 isonitrogenous-isoosmotic diets (amino acids, lactalbumin & its hydrolysate, casein & its hydrolysate), decrease of serum PHE with THI or PHE-ol only occurred with high PHE diets (inhibitor/PHE molar ratio 1.4), without significant difference between results with intact or hydrolysed protein diets. It has been claimed that amino acid (AA) changes in serum, liver and brain, induced by hyperPHE, could explain disturbed protein synthesis in PKU; we confirm such changes in our PKU model (mainly: essential AA decrease in serum, liver and brain), however AA imbalance did not disappear on THI or PHE-ol supplemented diets. These data suggest that PHE analogues (such THI or PHE-ol)used in diets to decrease intestinal absorption of PHE cannot ensure serum PHE reduction comparable to that obtained with PHE restricted diets. More... »

PAGES

175

Identifiers

URI

http://scigraph.springernature.com/pub.10.1203/00006450-198002000-00088

DOI

http://dx.doi.org/10.1203/00006450-198002000-00088

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050052312


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