Abstract

Our experiments were performed to determine whether human liver, like that of other mammals, could catalyze the N-sulfation of an arylamine, 2-naphthylamine (2-NA) and, if so, whether this reaction might be catalyzed by one or both of the two known forms of human phenol sulfotransferase (PST). One form of PST is thermostable (TS) and catalyzes the sulfation of "simple" phenols such as p-nitrophenol, while the other form is thermolabile (TL) and catalyzes the sulfate conjugation of phenolic monoamines such as dopamine. When 2-NA that was not contaminated with 2-naphthol was used as substrate, human hepatic cytosol could catalyze the N-sulfation of 2-NA with an apparent Km of 322 microM. However, substrate kinetics of the sulfate donor for the reaction, 3'-phosphoadenosine-5'-phosphosulfate, were biphasic, with estimated apparent Km values of 0.13 and 2.2 microM for high and low affinity activities, respectively. Human liver arylamine N-sulfotransferase (AANST) activity was similar to that of TS but not TL PST with regard to thermal stability, inhibition by 2,6-dichloro-4-nitrophenol (DCNP), and regulation among individuals. For example, average temperatures that produced 50% inactivation of TL PST, TS PST, and AANST activities, measured with both 0.05 and 1.0 mM 2-NA as substrate, were 35.0, 40.5, 40.3 and 40.5 degrees C, respectively. IC50 values for the inhibition by DCNP of TL PST, TS PST, and AANST, measured with 0.05 and 1.0 mM 2-NA as substrate, were 110, 1.8, 1.3, and 4.0 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)