Chronic Hyperphenylalaninemia Produces Cerebral Hyperglycinemia in Immature Rats

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Abstract
The amino acid content of 3 tissues was measured in 10 day old rats made hyperphenylalaninemic from 3-10 days old by daily injections of phenylalanine and .alpha.-methylphenylalanine to inhibit phenylalanine hydroxylase (PAH). At 12 h after the last injection the concentrations of alanine, valine, methionine, isoleucine and leucine in the cerebral hemispheres were depressed by 25-50%, glycine was elevated 2.3-fold. In the spinal cord the levels of phosphoserine, methionine and leucine were decreased by 40-50%, serine and threonine increased by 50%. Tyrosine and phenylalanine concentrations were high in all tissues, 2-3 and 15-30 times normal, respectively; of the amino acids included, they were the only ones changed in the liver. Cerebral hyperglycinemia was produced by chronic treatment with phenylalanine and p-chlorophenylalanine to inhibit PAH but not by acute (12 h) hyperphenylalaninemia. An increase in cerebral phosphoserine phosphatase activity was greater in rats treated with phenylalanine and PAH inhibitor than with only inhibitor. The content of brain glycine normally declines with age from birth to 15 days; this decrease was prevented by chronic hyperphenylalaninemia. Attempts to reduce the cerebral glycine content of the hyperphenylalaninemic rats were unsuccessful. A therapeutic protocol, methionine loading, may be useful since it increased the methionine and decreased the phenylalanine contents in the brain.