Dependence of 5-HT and catecholamine synthesis on concentrations of precursor amino-acids in rat brain

Summary The short-term influence of varying concentrations of the precursors tryptophan and tyrosine on the formation of 5-hydroxytryptophan and Dopa, respectively, in three different rat-brain regions was investigated. The concentrations of the precursors were either increased by the intraperitoneal administration of the respective precursor or decreased by loading with large neutral amino acids competing with the precursors for the same carrier mechanisms.The formation of 5-hydroxytryptophan was found to depend on the level of tryptophan in the brain in a manner predicted from published kinetic data, except when large doses of non-precursor amino acids had been given (>300 mg/kg). In the latter case the hydroxylation of tryptophan was less rapid than expected. The apparent K _m of tryptophan hydroxylase calculated from these data was about 25 M, which is in reasonably good agreement with earlier published in-vitro and in-vivo data.The formation of Dopa likewise depended on the level of the precursor tyrosine in a predictable manner, in this case without any anomalous results after large doses of non-precursor amino acids. The apparent K _m of tyrosine hydroxylase was calculated from these invivo observations to be about 25 M, which is in fairly close agreement with published in-vitro data.It is concluded that under normal conditions tryptophan hydroxylase in the rat brain is about half-saturated with its amino-acid substrate, whereas tyrosine hydroxylase appears to be about 75% saturated.