Studies on the experimental phenylketonuria in rats.

Wister albino pregnant rats were fed on pellets containing 3.5% L-phenylalanine (Phe) from 10 days before the expected date of birth. The diet was then switched to 7% Phe pellets at the third week after birth. Baby rats were reared with breast milk, and weaned at the end of the 4th week after birth; thereafter, they were reared with a normal diet for one week at the 5th week, and then were given 7% Phe diet from the 6th week. These rats, which were reared with a diet of high Phe, showed a similar metabolic pattern to that of human phenylketonuria (PKU) in the following aspects: definite suppression of the liver Phe hydroxylase activity, excretion of a large amount of phenylpyruvic acid (PPA) and phenyllactic acid (PLA) into urine, and an elvated level of blood Phe content. But, they had an excessive amount of blood tyrosine (Tyr), and concurrently excreted massive homogentisic acid (HGA) in urine just as in human tyrosinemia alkaptonuria. The absence of urinary o-hydroxyphenylacetic acid (o-HPAA) was also a distinct difference from human PKU. In some rats, mild inhibition of the liver Phe hydroxylase activity was observed. In other rats, there was no excretion of PPA into urine as in human hyperphenylalaninemia. Further, the regulatory mechanism of Phe catabolism of experimental PKU was discussed by analysing the enzyme activity of the liver Phe hydroxylase, phenylalanine-pyruvate (Phe-Pyr) transaminase and tyrosine alpha-ketoglutarate (Tyr-alpha-Kg) transaminase at different developmental stages of the rats.