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Eventually, in some dogs, systolic failure develops from the chronic volume overload

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As detailed in Section 2.1, GGT-mediated hydrolysis of the γ-glutamyl bond initiates the extracellular γ-glutamyl cycle, ultimately recycling cysteine, glycine, and glutamate back into the cell for renewed GSH synthesis [75] Of note in the context of the Glu-GSH axis, GGT activity represents a quantitatively significant route by which glutamate is regenerated from exported GSH: GGT is predominantly expressed on the plasma membrane of hepatocytes, renal tubular cells, and intestinal epithelial cells, where this recycling mechanism maintains precursor availability for continuous GSH resynthesis [27]