RESUMEN
Hypertryptophanemia is a rare inherited metabolic disorder probably caused by a blockage in the conversion of tryptophan to kynurenine, accumulating tryptophan and some of its metabolites in plasma and tissues of affected patients. The patients present mild to moderate mental retardation with exaggerated affective responses, periodic mood swings, and apparent hypersexual behavior. Pyruvate kinase catalyses a critical step in the glycolysis pathway, the main route that provides energy to brain functioning. The main objective of the present study was to determine pyruvate kinase activity in brain cortex of rats subjected to acute chemically induced hypertryptophanemia. The effect of alanine administration to the treated rats on the enzyme activity was also investigated. We also studied the in vitro effect of the two amino acids on pyruvate kinase activity in the brain cortex of nontreated rats. The results indicated that tryptophan inhibits pyruvate kinase in vitro and in vivo and that alanine prevents this inhibitory effect on the enzyme activity. Considering the crucial role pyruvate kinase plays in glucose metabolism in brain, it is possible that inhibition of this enzyme activity may contribute to the brain damage characteristic of this disease. Further studies will be necessary to evaluate possible benefits of alanine administration to the patients affected by hypertryptophanemia.