Some properties of bovine pineal tryptophan hydroxylase.

Abstract

Bovine pineal tryptophan hydroxylase is a pterin-dependent aromatic amino acid monooxygenase with a broad substrate specificity and with low Km values for the amino acid substrates, L-tryptophan and L-phenylalanine. p-Chlorophenylalanine, an inhibitor of the tryptophan hydroxylation in the brain, also serves as a good substrate of the bovine pineal enzyme. The full activity of this enzyme is detected in vitro only after preincubation with dithiothreitol under reductive conditions. The enzyme is profoundly and more or less specifically inhibited by L-5HTP, the product of tryptophan hydroxylation, suggesting a possible regulatory role of this hydroxylated amino acid. The Km of the enzyme for tetrahydrobiopterin, a presumed natural cofactor, is significantly higher than the expected tissue concentration if the cofactor is assumed to be uniformly distributed in the tissue. These properties of bovine pineal tryptophan hydroxylase are distinguishable from those of the hydroxylase in the brain indicating that the hydroxylation of tryptophan in the brain leading to the synthesis of serotonin and the reaction in the pineal gland leading to the formation of melatonin are catalyzed by different tryptophan hydroxylases and are probably under separate regulatory mechanisms.