Garay, E., Schuth, N., Barbanente, A., Tejeda-Guzmán, C., Vitone, D., Osorio, B., Clark, A.H., Nachtegaal, M., Haumann, M., Dau, H., Vela, A., Arnesano, F., Quintanar, L., Missirlis, F. (2022). Tryptophan regulates Drosophila zinc stores.  Proc. Natl. Acad. Sci. U.S.A. 119(16): e2117807119.

FBrf0253150

Research paper

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.

PMC9169789 (PMC) (EuropePMC)