Interaction between the oxygen and tryptophan dependence of synaptosomal tryptophan hydroxylase.

The substrate dependence of tryptophan hydroxylase activity in rat striatal synaptosomes was examined. The Km for tryptophan in air to 8--13 microM, comparable to the concentration present in cerebrospinal fluid. The reaction is inhibited by amino acids with large nonpolar side chains. For leucine the inhibition appears competitive; it results from a decrease in the steady state levels of intrasynaptosomal tryptophan. The oxygen Km at 10 microM-tryptophan is 3--4 mm Hg, which is increased when the reaction is assayed with low levels of tryptophan in the medium, and in the presence of amino acids such as leucine. Similarly, the tryptophan Km is increased at low oxygen tensions; at 9 mm Hg of oxygen it is 23 microM. These interactions between tryptophan and oxygen dependence of the reaction are discussed in terms of likely physiological significance and implications for the pharmacological use of tryptophan.