**Fund support**

hydroperoxide) used as substrate of the reaction. In the presence of 100 μM l‐penicillamine hydantoin, the enzyme reactions catalyzed by glutathione peroxidase were inhibited, but neither glutathione transferases, nor glutathione reductase were affected by l‐penicillamine

dl‐Buthionine‐[*S, R*]‐sulfoximine (BSO) can be used as an inhibitor to estimate the scavenging efficiency of H2O2 after GPX inhibition. The inhibitory effect did not act on GPX directly, but through suppress the synthesis of GSH by inhibiting γ‐glutamylcysteine synthetase, that cause glutathione decreased sharply in many tissues, especially kidney, liver, and pancreas [53]. BSO has an obvious inhibitory effect, for example in human fibroblasts cells, after 500 μM BSO treated, the GSH levels decreased to154.0 ± 16.9 nmol/mg protein from 418.4 ± 13.1 nmol/mg

Gold(I) thioglucose in the presence excess of glutathione (GSH) leads to strong and reversible inhibition of selenium‐GPXs. Gold(I) could competitively combine in reduced form of selenocysteine in active sites, and gold(I) forms a dead‐end complex with glutathione perox‐ idase resulting in suppression of GPXs. So glutathione peroxidase could be a target of gold drugs that used in the treatment of disease caused by excessive activity of GPXs, such as

To our knowledge, most literature studies on enhancing GPXs activity were about how to regulate expression of GPXs, study on the activator by acting the enzyme directly was few and

For some GPX mimetics, its activity can be enhanced by electron‐donating. naphthalene *peri*‐ diselenide mimeticswas increased by electron‐donating methoxy substituents, while a further 100‐fold increase was observed with the corresponding ditelluride. This was attributed to the ability of the methoxy group to stabilize the increasing positive charge at the selenium atom during the rate‐determining step of the catalytic cycle, which involves the oxidation of Se(II) to Se(IV), thus improved their catalytic activity to levels comparable with their aliphatic counterparts [56]. Others report that 6‐bromo‐substituted diselenides also enhanced its activity by threefold [57]. Another strategy is to change the aqueous solubility of the mimetics. Diaryl selenides containing *o*‐hydroxymethylene substituents function as peroxide‐destroying mimetics of the antioxidant selenoenzyme glutathione peroxidase. Several selenide analogues

hydantoin [52].

218 Enzyme Inhibitors and Activators

protein [54].

*4.4.2.2. Gold(I) thioglucose*

rheumatoid arthritis [55].

**4.5. Activators of GPXs**

most of them are GPX‐mimetic compounds.

*4.5.1. Enhance activity of GPX mimetics*

*4.4.2. Noncompetitive inhibitors*

*4.4.2.1. dl‐Buthionine‐[S, R]‐sulfoximine*

This work was supported by grants from the Key project of Natural Science Foundation of Guangdong Province (2014A030311010), Guangdong Province Modern Agro‐industry Technology Research System (2016LM1080)
