Add time:09/24/2019         Source:sciencedirect.com

Suckling rats were injected subcutaneously with doses of L-ETHIONINE (cas 13073-35-3) (0.1 μmole/g body wt and 0.5 μmole/g body wt) at intervals of 12 hr. In the latter group, phenylalanine hydroxylase was effectively inhibited in vivo resulting in hyperphenylalaninemia and phenylketonuria. Due to the well-known sex-specific differences in l-ethionine metabolism female rats were much more affected by chronic administration of l-ethionine.The underlying mechanism of enzyme inhibition by ethionine could be disturbed protein synthesis and impaired protein phosphorylation, which was suggested by pronounced decreases in ATP content in liver. In the high dosage group depletions mainly of the branched-chain amino acids and lysine occurred in serum and brain, whereas the concentrations of methionine and tryptophan were increased. Tyrosine tended to be decreased in the course of hyperphenylalaninemia.Hyperphenylalaninemia and other resulting amino acid imbalances obviously impaired brain development during the early postnatal period. Concomitantly with reductions in protein concentrations, the activity of cathepsin D, a major intralysosomal acid proteinase, was increased in brain, suggesting also higher protein catabolism in brain. Side effects of this treatment, however, were higher mortality, loss of body weight, and a general impression of delayed development, resembling a state of undernutrition to some extent. These obvious side effects of ethionine limit the usefulness of ethionine as a suitable model for classic phenylketonuria in suckling rats.

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