Inhibition of human sulfotransferases (SULTs) by per- and polyfluoroalkyl substances (PFASs) and structure-activity relationship.

Per- and polyfluoroalkyl substances (PFASs) are a family of highly fluorinated aliphatic substances widely used in industrial and commercial applications. This study aims to determine the inhibition of PFASs towards sulfotransferases (SULTs) activity, and trying to explain the toxicity mechanism of PFASs. In vitro recombinant SULTs-catalyzed sulfation of p-nitrophenol (PNP) was utilized as a probe reaction. The incubation system was consisted of PFASs, SULTs, PNP, 3'-phosphoadenosine-5'-phosphosulfate, MgCl and Tris-HCl buffer. Ultra-performance liquid chromatography was employed for analysis of the metabolites. All tested PFASs showed inhibition towards SULTs. The longer the carbon chain length of the PFASs terminated with -COOH, the higher is its capability of inhibiting SULT1A3. PFASs with -SOH had a relatively higher ability to inhibit SULT1A3 activity than those with -COOH, -I and -OH. The inhibition kinetic parameter was 2.16 and 1.42 μM for PFOS-SULT1A1, PFTA-SULT1B1. In vitro in vivo extrapolation showed that the concentration of PFOS and PFTA in human matrices might be higher than the threshold for inducing inhibition of SULTs. Therefore, PFASs could interfere with the metabolic pathways catalyzed by SULTs in vivo. All these results will help to understand the toxicity of PFASs from the perspective of metabolism.