Multiple forms of aryl sulfotransferase for acetaminophen sulfate conjugation in rat liver cytosol.

Abstract

The multiplicity of aryl aulfotransferase (phenol sulfotransferase, PST) in acetaminophen (APAP) sulfate conjugation was studied in rat liver cytosol. The sulfation rate showed the optimal pH of about 9 similar to that in the phenolic monoamine sulfation. And another optimal pH of about 6.4 was found at the higher APAP concentration such as 16 mM, suggesting the existence of the PST multiplicity in the APAP sulfation. The effect of thermal treatment at various temperatures, 37 to 41°C, showed that PST catalyzing the sulfation at the lower APAP concentration (about less than 1 mM) is more thermolabile and has the lower K_m for APAP than at the higher APAP concentration. The APAP sulfation at μM order APAP in the presence of p-nitrophenol (PNP) was shown to be decreased by the substrate inhibition of PNP to PST. Consequently it is considered the sulfation at the lower APAP concentration (μM order) is mainly catalyzed by the thermolabile PST with the lower K_m for APAP, and at the higher APAP concentration the thermostable PST with the higher K_m partially contributes to the sulfation.