2.B.97.  The Metal Ion Ionophore, Pyrithione (Pyrithione) Family 

Pyrithione (2-mercapto pyridine-N-oxide) is a heavy metal (Zn2+, Fe2+ and Cu2+) ionophore that transports itself with or without metal ions across cell membranes.  It can function as a metal ion uptake transporter because of the negative membrane potential in most cells including bacterial, archaea and eukaryotes. The reverse reaction, efflux of these ions can be catalyzed by CopA (a copper exporting ATPase; 3.A.3.5.5) and ZntA (a Zn2+ exporting ATPase (3.A.3.6.2). Two transporters, FepC (TC# 3.A.1.14.2) and MetQ (TC# 3.A.1.24.1) may be capable to taking up both pyrithione and its metal conjugates (Salcedo-Sora et al. 2021). Zinc-pyrithione activates the volume-regulated anion channel, VRAC (TC# 1.A.25.3.1)), through an antioxidant-sensitive mechanism (Figueroa and Denton 2021). A direct way to determine zinc transport kinetics using an assay based on a zinc-specific fluorescent dye, FluoZin-3 has been described (Ben Yosef et al. 2023).





Ben Yosef, T.E., R. Zarivach, and A. Moran. (2023). Characterizing Mammalian Zinc Transporters Using an In Vitro Zinc Transport Assay. J Vis Exp.

Figueroa, E.E. and J.S. Denton. (2021). Zinc pyrithione activates the volume-regulated anion channel through an antioxidant-sensitive mechanism. Am. J. Physiol. Cell Physiol. 320: C1088-C1098.

Salcedo-Sora, J.E., A.T.R. Robison, J. Zaengle-Barone, K.J. Franz, and D.B. Kell. (2021). Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in. Molecules 26:.