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.