title: 2,6-Dichloro-4-nitrophenol (DCNP), an alternate-substrate inhibitor of phenolsulfotransferase.
abstract: 2,6-Dichloro-4-nitrophenol (DCNP)-35sulfate was identified and quantified by an HPLC-radiometric assay following its biosynthesis in vitro from 35S-labeled 3'-phosphoadenosine-5'-phosphosulfate (PAP35S) by phenolsulfotransferase (PST) of rat liver cytosol. Acid hydrolysis of DCNP-35sulfate produced almost stoichiometric release of inorganic 35sulfate and DCNP. In two-substrate experiments of sulfation of p-nitrophenol (p-NP) or dopamine (prototype substrates for P and M human PST forms), 10 microM DCNP inhibited the reactions by about 15 and 78%, respectively. This contrasts with its action on PST of human origin where the P-PST was more sensitive to DCNP inhibition. In all mixed bi-substrate experiments, a reciprocal relationship between the two sulfated products was observed. Kinetic data showed that p-NP inhibited the sulfation of DCNP competitively. Likewise the sulfation of p-NP and dopamine was competitively inhibited by DCNP. However, non-competitive inhibition was observed in the sulfation of p-NP by DCNP, measured at varying concentrations of PAP35S. The above kinetic data suggest that DCNP is an alternate-substrate inhibitor of rat liver PST.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, National University of Singapore, Kent Ridge.
authors.forename: V M
authors.initials: VM
authors.lastname: Seah
authors.forename: K P
authors.initials: KP
authors.lastname: Wong
mesh_terms: D000818:Animals; D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors*; D003600:Cytosol / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism; D006247:Harmine / Q000031:analogs & derivatives / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D009596:Nitrophenols / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013431:Sulfates / Q000378:metabolism*
chemical_list: D009596:Nitrophenols; D013431:Sulfates; C001326:harmol; D006247:Harmine; C015802:2,6-dichloro-4-nitrophenol; D015239:Arylsulfotransferase; D004298:Dopamine; C024836:4-nitrophenol