2,6-DICHLORO-4-NITROPHENOL (DCNP), AN ALTERNATE-SUBSTRATE INHIBITOR OF PHENOLSULFOTRANSFERASE

被引：24

作者：

SEAH, VMY ^{[1
]}

WONG, KP ^{[1
]}

机构：

[1] NATL UNIV SINGAPORE,FAC MED,DEPT BIOCHEM,SINGAPORE 0511,SINGAPORE

来源：

BIOCHEMICAL PHARMACOLOGY | 1994年 / 47卷 / 10期

关键词：

DCNP; PHENOLSULFOTRANSFERASE (PST); RAT LIVER; DOPAMINE;

D O I：

10.1016/0006-2952(94)90301-8

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

2,6-Dichloro-4-nitrophenol (DCNP)-(35)sulfate was identified and quantified by an HPLC-radiometric assay following its biosynthesis in vitro from S-35-labeled 3'-phosphoadenosine-5'-phosphosulfate (PAP(35)S) by phenolsulfotransferase (PST) of rat liver cytosol. Acid hydrolysis of DCNP-(35)sulfate produced almost stoichiometric release of inorganic (35)sulfate 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 mu M 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 PAP(35)S. The above kinetic data suggest that DCNP is an alternate-substrate inhibitor of rat liver PST.

引用

页码：1743 / 1749

页数：7