Effect of experimental hyperphenylalaninemia on biogenic amine synthesis at later stages of brain development

The effects of experimental hyperphenylalaninemia on catecholamine and serotonin synthesis in brain at a later stage of brain development were investigated. A group of 35-day-old rats treated with normal chow supplemented with 5% Phe + 0.4% alpha-methylphenylalanine, alpha MP, for the previous 10 days showed decreases in dopa, norepinephrine, and epinephrine versus controls. A group treated with a normal diet supplemented with 0.4% alpha MP showed similar decreases and these differences could be attributed to the presence of the phenylalanine hydroxylase and tyrosine hydroxylase inhibitor, alpha MP, rather than the hyperphenylalaninemia condition. No differences in dopamine were observed. Serotonin and 5-hydroxyindoleacetic acid (5HIAA) were decreased 50% in the HyPhe condition and were unaffected in the presence of alpha MP alone, indicating that the decreases in serotonin and 5HIAA were due to the increases in phenylalanine rather than the presence of the inhibitor. These abnormalities in serotonin metabolism at later stages of brain development may be relevant to early discontinuation of dietary therapy in the PKU patient and implies a role in tryptophan supplementation to increase intracerebral serotonin values.