New discoveries into how the body stores zinc

Confocal images of the kidney-like Malpighian tubule from a Drosophila larva at two magnifications. More details below the article.

Confocal images of the kidney-like Malpighian tubule from a Drosophila larva at two magnifications. More details below the article. © Erika Garay (Cinvestav)

Zinc deficiency is a global health problem affecting many people and results in a weak immune system in adults and especially in children. This is a challenge for health systems and is quite evident in the Mexican population, for example. Seeking explanations, researchers in Mexico teamed up with international synchrotron experts and gained new insights from studying Drosophila fruit flies, which are known to be a decent model system for human zinc metabolism.
Thanks to beamtime at BESSY II and at the SLS (PSI), they were able to show that the zinc stores in Drosophila flies depend on the tryptophan content of their diet.

“The first experiments were done on the KMC-3 spectroscopy beamline,” relates DFG Fellow Nils Schuth, who is currently researching in Mexico at the Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav). “We took organs from a fruit fly and performed direct measurements of the tissue. We gained very revealing information from the data. That was the first step, which already brought us forward. In a second step, we then compared the biological results with various synthesised chemical complexes.”

The project started in 2019. Then came the pandemic and travel restrictions. The next measurements were therefore performed at the Paul Scherrer Institute (PSI) on the SLS, where the two research institutes were already cooperating. In the spring of 2021, new measurements performed at BESSY II confirmed their discoveries.

Nils Schuth is thrilled with the experimental results, which now bridge a gap between chemical processes and biological functions. “The measurements at the two light sources allowed us to make a comparison of material that was isolated from flies with or without a zinc store.” These studies reveal the existence of a new chemical complex of zinc with 3-hydroxykynurenine (a tryptophan product) and chloride, which is essential for zinc storage.

The research on fruit flies is a significant contribution towards better understanding zinc retention in humans, and could help in developing dietary supplements. “Our results could even help in the treatment of COVID-19 because many people with the disease are also suffering from a zinc deficiency and upset tryptophan levels,” emphasises Nils Schuth.

Additional information about the picture:

Visible in red are the cell nuclei (large circles) and the tryptophan products 3-hydroxykynurenine and xanthurenic acid (little circles). Visible in green are the zinc transporters of the cells, which indicate a high concentration of zinc. The fact that the little red circles appear within green circles indicates that zinc accumulates in storage granules together with 3-hydroxykynurenine and xanthurenic acid. The experiments at BESSY II confirmed that zinc forms a chemical complex with 3-hydroxykynurenine and chloride. The results suggest that tryptophan-derived metabolites play an important role in the intracellular retention of zinc.

A detailed report on this research exists in Spanish and English: https://fanismissirlis.blog/2022/04/11/chemical-complex-regulates-body-zinc/

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