Free tryptophan in serum controls brain tryptophan level and serotonin synthesis

Abstract Tryptophan (Try) is the only aminoacid present in plasma bound to serum proteins. The administration of Try to rats increased free and total Try in serum. Changes in free Try were much more pronounced and longer lasting than in total Try. Brain Try and 5-hydroxyindoleacetic acid (5-HIAA) underwent changes, parallel and proportional to the changes in free Try in serum. Rats fasted for 24 hours had higher concentrations of free serum tryptophan, brain tryptophan and 5-HIAA than rats fed for 2 hours. In contrast, total serum tryptophan was lower in fasted than in fed rats. These results indicate that brain tryptophan and serotonin turnover are controlled by free serum tryptophan and that free serum tryptophan levels are independent from total serum tryptophan concentrations.