Zinc Alleviates Gut Barrier Dysfunction by Promoting the Methylation of AKT.

ABSTRACT: Zinc plays a crucial role in the gut barrier function and are widely used for the prevention of bowel disease. However, the mechanism via which zinc supplementation exerts this regulatory effect is unclear. The present study identifies and characterizes the zinc-responsive activation of AKT and demonstrates its function in alleviating gut barrier dysfunction. Mechanistically, zinc increased intracellular SAM production, a methyl donor, by promoting the activation of the metallochaperone ZNG1-METAP1 complex. Subsequently, zinc facilitates methylation (symmetrical dimethylarginine, SDMA) of AKT at residues R391 and R15, which is facilitated by PRMT5. The AKT^SDMA modification promotes AKT translocation from the cytoplasm to the plasma membrane and its interaction with mTORC2, ultim

SUBMITTER: Cai C 

PROVIDER: S-EPMC12412578 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature