GGL Inhibitors

GGL inhibitors encompass a range of chemicals specifically designed to thwart the biochemical pathways mediated by gamma-glutamyltransferase 5 (GGL). The first chemical, Acivicin, competitively binds to the active site of GGL, the cleavage of gamma-glutamyl moieties from glutathione. Acivicin achieves this by mimicking the structure of glutathione and occupying the enzyme's active site, which makes it unable to process its natural substrate.

The second compound, 6-Diazo-5-oxo-L-norleucine (DON), operates on a different principle. As a glutamine antagonist, it not only inhibits GGL but also disrupts other enzymes that rely on glutamine as a substrate. When DON competes with glutamine for binding to GGL, the enzyme's ability to convert leukotriene C4 to leukotriene D4 is inhibited. L-serine-borate complex, another inhibitor, forms a tetrahedral transition state analog with the enzyme. This analog occupies and blocks the active site of GGL, rendering it catalytically inactive. By doing so, the L-serine-borate complex interferes with the enzyme's capability to perform its specialized reactions, such as the cleavage of gamma-glutamyl moieties and the conversion of leukotrienes. Therefore, these compounds achieve GGL inhibition either by competitive inhibition, substrate antagonism, or by directly impeding the enzyme's catalytic action.