Tryptophan regulates <i>Drosophila</i> zinc stores
Erika Garay, Nils Schuth, Alessandra Barbanente, Carlos Tejeda-Guzmán, Daniele Vitone, Beatriz Osorio, Adam H. Clark, Maarten Nachtegaal, Michael Haumann, Holger Dau, Alberto Vela, Fabio Arnesano, Liliana Quintanar, Fanis Missirlis
Abstract
Zinc deficiency is commonly attributed to inadequate absorption of the metal. Instead, we show that body zinc stores in Drosophila melanogaster depend on tryptophan consumption. Hence, a dietary amino acid regulates zinc status of the whole insect—a finding consistent with the widespread requirement of zinc as a protein cofactor. Specifically, the tryptophan metabolite kynurenine is released from insect fat bodies and induces the formation of zinc storage granules in Malpighian tubules, where 3-hydroxykynurenine and xanthurenic acid act as endogenous zinc chelators. Kynurenine functions as a peripheral zinc-regulating hormone and is converted into a 3-hydroxykynurenine–zinc–chloride complex, precipitating within the storage granules. Thus, zinc and the kynurenine pathway—well-known modulators of immunity, blood pressure, aging, and neurodegeneration—are physiologically connected.