Liver tryptophan pyrrolase activity and metabolism of brain 5-HT in rat

Abstract

TRYPTOPHAN is the amino acid precursor of 5-hydroxytryptamine (5-HT) both peripherally and in the central nervous system, but the metabolism of tryptophan by way of the 5-HT pathway accounts for only 1 % of urinary tryptophan metabolites¹. The major route of tryptophan metabolism starts with its conversion to formylkyneurenine by tryptophan pyrrolase², and it has been suggested^3,4 that depressive illness may be caused by the induction of liver tryptophan pyrrolase by plasma corticosteroids⁵, leading to decreased synthesis and turnover of 5-HT in the brain. We confirm the increase in activity of liver tryptophan pyrrolase produced by hydrocortisone and the decrease in activity by allopurinol reported by Curzon and Green². Hydrocortisone also increased the concentration of ‘free’ tryptophan in the serum. Although the concentration of 5-HT in the brain was unchanged, tryptophan and 5-hydroxyindole acetic acid (5-HIAA) concentrations in the brain were also increased. ‘Free’ and total tryptophan concentrations in the serum were reduced by allopurinol injection, but concentrations of tryptophan in the brain were unchanged. These results are not compatible with the theory that the induction of liver pyrrolase by hydrocortisone induces the symptoms of depressions.