2,6-二氯-4-硝基苯酚（DCNP），一种酚磺基转移酶的替代底物抑制剂。

2,6-Dichloro-4-nitrophenol (DCNP), an alternate-substrate inhibitor of phenolsulfotransferase.

作者信息

Seah V M, Wong K P

机构信息

Department of Biochemistry, Faculty of Medicine, National University of Singapore, Kent Ridge.

出版信息

Biochem Pharmacol. 1994 May 18;47(10):1743-9. doi: 10.1016/0006-2952(94)90301-8.

DOI:10.1016/0006-2952(94)90301-8

PMID:8204091

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.

摘要

通过大鼠肝细胞溶质的酚磺基转移酶（PST）在体外由35S标记的3'-磷酸腺苷-5'-磷酸硫酸酯（PAP35S）生物合成2,6-二氯-4-硝基苯酚（DCNP）-35硫酸盐后，采用高效液相色谱-放射测定法对其进行鉴定和定量。DCNP-35硫酸盐的酸水解几乎化学计量地释放出无机35硫酸盐和DCNP。在对硝基苯酚（p-NP）或多巴胺（人P和M型PST形式的原型底物）硫酸化的双底物实验中，10 microM DCNP分别使反应抑制约15%和78%。这与它对人源PST的作用形成对比，其中P-PST对DCNP抑制更敏感。在所有混合双底物实验中，观察到两种硫酸化产物之间存在倒数关系。动力学数据表明p-NP竞争性抑制DCNP的硫酸化。同样，DCNP竞争性抑制p-NP和多巴胺的硫酸化。然而，在不同浓度的PAP35S下测定时，观察到DCNP对p-NP硫酸化存在非竞争性抑制。上述动力学数据表明DCNP是大鼠肝脏PST的一种替代底物抑制剂。