The effect of hyperphenylalaninaemia on glycine metabolism in developing rat brain.

The brains of 3--16-day-old rats that were rendered hyperphenylalaninaemic by daily injections of alpha-methylphenylalanine plus phenylalanine were subjected to biochemical analysis. Fluctuations throughout the treatment period in the concentrations of branched-chain amino acids, methionine and serotonin were in agreement with the known interference of excess plasma phenylalanine with transport. The glycine content, however, became abnormal only by day 5, remained so through the treatment, and the elevation was equally apparent at 4, 8 or 24 h after the last daily injections. On the last day of treatment there were small increases in the taurine, glutamate, aspartate and 4-aminobutyrate concentrations, attributable mainly to the diencephalon or brain stem. After day 3 of treatment there were persistent elevations in the specific activity of phosphoserine phosphatase and glycine synthase (but not serine hydroxymethyltransferase) of the brain in each of the regions analysed. The observations indicate that chronic hyperphenylalaninaemia interferes with the normal regulation of intracerebral glycine metabolism during a critical period of early postnatal development, and suggest that the resulting excess in this amino acid (particularly marked in the cortex) contributes to the behavioural abnormalities that these animals exhibit in later life.