The Effect of High Dietary Phenylalanine on the Concentration of Brain and Liver Serotonin and Nicotinamide Adenine Dinucleotide in Rats

Fifty-four weanling Long-Evans-Sprague-Dawley rats were fed a niacin-free, 12 percent casein basal diet for one week. At the end of the pre-experimental adjustment period each rat was assigned to one of seven groups so that the average weight per group did not differ by more than one or two grams. Three of the seven groups ("A," "B" and "C") were fed the experimental diets (basal supplemented with L-phenylalanine to 3, 5 and 7 percent levels). One group of rats ("BC") was fed the basal diet (0 .62 percent L-phenylalanine) ad libitum. Feed consumption of all rats fed the experimental diets was measured daily and rations of basal diet equal to the amounts eaten by experimental rats were given to the pair-fed control rats ("AA," "BB" and "CC"). At the end of the two-week experimental period the rats were sacrificed by decapitation. The right hemisphere of the brain was used for the analysis of NAD and the left hemisphere for serotonin assay. Liver (two separate lobes) samples were taken for serotonin and NAD analysis.

The effect of high levels of L-phenylalanine on feed consumption, weight gain, the concentration of serotonin in brain and liver, and the concentration of NAD in brain and liver were studied. The major purposes of this research were twofold: (1) To study the effect of excess amounts of L-phenylalanine on the kynurenine pathway of tryptophan metabolism, and (2) To study the relationship between the two major metabolites of tryptophan metabolism, serotonin and NAD, in the same animal as affected by high levels of L-phenylalanine.

As the percentage of L-phenylalanine in the diet increased to 5 and 7 percent, the feed consumption and weight gain decreased respectively in relation to rats fed the basal control diet. The decrease in feed consumption was significant (P<0.005) for rats fed the 7 percent L-phenylalanine diet and approached significance for rats fed the diet containing 5 percent L-phenylalanine. Decreased feed consumption and growth depression might be attributed to the excess amounts of L-phenylalanine.

The concentration of both brain and liver serotonin decreased in relation to the values obtained for "BC" and pair-fed basal ("AA, " "BB" and "CC") rats as the level of L-phenylalanine in the diet increased from 3 to 7 percent. The greatest differences were found at the 5 and 7 percent levels of L-phenylalanine.

The only significant difference (P<0.005) in the concentration of brain NAD of the experimental rats as compared to rats fed the basal control diet was the decrease demonstrated by rats ("A") fed the 3 percent level of L-phenylalanine. It might appear that L-phenylalanine fed at the 3 percent level either caused more tryptophan to enter the serotonin pathway than the kynurenine pathway in the brain or that the low concentration of NAD found in "A" rats might be attributed to failure of NAD already formed in the liver to pass from the blood stream to the brain.

The decreased concentration of liver NAD in rats fed the diet containing 7 percent L-phenylalanine might be attributed to decreased feed intake as a result of an excess of the amino acid in the diet. It appears that the failure of the concentration of liver NAO of rats in group "B" to decrease as expected due to decreased tryptophan intake might be a result of the 5 percent level of L-phenylalanine causing more tryptophan to enter the NAO pathway of tryptophan metabolism than entered the serotonin pathway.

The mean total brain weight and serotonin content of brain decreased significantly in rats fed diets containing 5 and 7 percent levels of L-phenylalanine. These reductions might not be attributed to decreased feed consumption alone but also to the level of L-phenylalanine in the experimental diets. A tendency for the NAD content to increase from the significantly low content found in "A" rats toward values comparable to that found in rats fed the basal control diet was demonstrated.

It appears that higher levels of L-phenylalanine (5 and 7 percent) decreased feed consumption, weight gain, brain size and serotonin content while NAD was decreased at the 3 percent level. Thus it seems that the higher levels of L-phenylalanine (5 and 7 percent) might have caused more of the tryptophan eaten to enter the kynurenine pathway of tryptophan metabolism with a correspondingly smaller amount entering the serotonin pathway. The opposite relationship was indicated for the 3 percent level of L-phenylalanine.