Influence of Phenylalanine Administration on the Free Amino Acids of Brain and Liver in the Rat

Abstract

RECENT studies have indicated that L-phenylalanine inhibits antibody response to diphtheria toxoid in rats and rabbits ( RYAN and CARVER, 1964). It was suggested, as an explanation for the inhibition, that excess phenylalanine caused a disturbance in the free amino acids of the animals with a resultant decrease in antibody (protein) synthesis. It is also conceivable that chronic alterations in the amino acids of the central nervous system induced by phenylalanine could also give rise to changes in protein synthesis. Since an excess or deficiency of an amino acid might exert an effect on the distribution of other amino acids, a quantitative study of the amino acids in rat brain and liver was conducted to assess the influence of phenylalanine on the concentration of the other amino acids. METHODS L-Phenylalanine (Nutritional Biochemical) was dissolved in dilute HC1-saline, neutralized with NaOH and brought to volume. All injections were made intraperitoneally in a volume not exceeding 2.0 ml. Sprague-Dawley male rats weighing between 150-175 g were used. The control animals received saline; the experimental groups were injected with 100 mg L-phenylalanine. At 15, 30, and 120 min after injection, the rats were placed under light ether anaesthesia, a midline incision was made, the heart was exposed and blood was removed by cardiac puncture. The hepatic vein and spinal cord were clamped with haemostats, and saline was perfused through the heart for 5 sec to free the brain of blood (CHIIUGOS, GREENGARD and UDENFRIEND, 1960). The animals were sacrificed, the brains and livers were quickly removed and blotted with filter paper, and the free amino acids were isolated with minor modifications according to TALLAN, MOORE and STEIN (1956) and quantitated by ion-exchange chromatography (SPACKMAN, STEIN and MOORE, 1958). RESULTS 45

The Effects of Hyperphenylalaninemia on Fetal Development: a New Animal Model of Maternal Phenylketonuria

“…The only well understood mechanism underlying chemical alterations in the brains of phenylketonurics, and of animal models of the disease, is the inhibition by excess phenylalanine of the cerebral uptake of amino acids sharing a common transport system (3,6,33,41). The present results show that this mechanism is operative in the 22-day-old fetus as well (see methionine, leucine, isoleucine and valine in Table 4).…”

“…Observations on blood sampled at different times throughout the day indicated that this indeed was the case. The plasma phenylalanine levels of the pregnant rats on the experimental diet were highest during the dark period (i.e., at midnight, 2 A.M. or 6 A.M.). They were 30-50 and 6Wo lower at 10 P.M. and 6 P.M., respectively.…”

Some Biochemical Consequences of Feeding Excesses of Phenylalanine to Rats*

“…The fact that brain total alpha-amino nitrogen was not altered in these experiments, despite elevated phenylalanine and tyrosine, indicates that aggravated imbalance of other brain amino acids cau occur in animals with raised pheuylalanine levels (cf. Carver, 1965;Boggs and McKean. 1965).…”

Alteration in Composition of Deoxyribonucleic Acid, Ribonucleic Acid, Proteins, and Amino Acids in Brain of Rats Fed High and Low Phenylalanine Diets

“…The concentration of aniino acids in brain is very sensitive to phenylalanine levels as shown by changes in the brain free aniino acids content caused by a single injection of i.-phcnylalaninc [3]. In our experiments, prolonged high levels of phenylalanine in plasma and correspondingly high concentration in the brain resulted in a pronounced increase in tyrosinc in brain and in a significant depletion of cerebral pools of valine, methionine, isoleucine, and leucine.…”