The thyroid hormone converting enzyme human deiodinase 1 is inhibited by gold ions from inorganic salts, organic substances, and by small-size nanoparticles.

The selenocysteine-containing enzyme class deiodinases (DIO) consists of three isoforms. DIOs play a role in regulation of thyroid hormone (TH) signaling through the removal of iodide from TH leading to TH that interact with the hypothalamic-pituitary-thyroid (HPT) axis with differing potency. Some gold-containing organic substances are known to inhibit many selenoenzymes, including DIOs. It is, however, unclear whether the Au-containing substances or the Au ions are causing the inhibition. In this study, five organic and inorganic gold substances as well as three gold nanoparticles (AuNPs) were tested for their potential to inhibit DIO1. The enzyme activity was tested using human liver microsomes as an enzyme source and reverse T3 as a substrate; iodide release was measured by the Sandell-Kolthoff method. The three organic gold substances aurothioglucose, auranofin and sodium aurothiomalate inhibited DIO1 with IC between 0.38 and 0.75 μM while their structural analogues lacking the gold ion did not. Likewise, the two tested gold salts, Au(I) and Au(III) chloride, showed a concentration-dependent inhibition of the DIO1 with IC values of 0.95 and 0.57 μM. Further, AuNPs of different sizes (100, 30 and 5 nm diameter) were tested with only the 5 nm AuNPs leading to inhibition with an IC of 8 × 10 AuNP/L. This inhibition was not caused by the Au ions released by the AuNP into the incubation media. The exact mechanism of inhibition of DIO1 by 5 nm AuNPs should be further examined. In conclusion, the microsomal DIO1 assay demonstrated the inhibition of DIO1 by gold ions originating from different gold-containing substances, but not by Au released from AuNPs; rather DIO1 is inhibited by 5 nm, but not larger, AuNPs.