Formation of melatonin and 5-hydroxyindole acetic acid from 14C-tryptophan by rat pineal glands in organ culture.

Abstract

THE rat pineal gland contains large amounts of serotonin1 and the enzymes tryptophan hydroxylase2 and aromatic 1-amino-acid decarboxylase3 which synthesize this indoleamine from tryptophan. We have reported that rat pineals in organ culture retain the ability to produce serotonin from its amino-acid precursors tryptophan and 5-hydroxytryptophan4. Most of the serotonin normally formed in the pineal is oxidized to 5-hydroxyindole acetic acid5 by the enzymes monoamine oxidase6 and aldehyde dehydrogenase. In addition, a portion of the indoleamine is N-acetylated7 and then converted to melatonin by hydroxyindole-O-methyl transferase8, an enzyme present in mammals only in the pineal gland9. By using isotopically labelled tryptophan as the substrate for our organ culture system, we have observed that such preparations can transform the serotonin produced to two end products: 5-hydroxyindole acetic acid (5HIAA) and melatonin.