Höer A, Oberdisse E
Institut für Pharmakologie der Freien Universität Berlin, Federal Republic of Germany.
Biochem J. 1991 Aug 15;278 ( Pt 1)(Pt 1):219-24. doi: 10.1042/bj2780219.
The influence of highly phosphorylated inositol phosphates on the Ins(1,3,4,5)P4 3-phosphatase enriched from the soluble fraction of pig brain was tested, using [5-32P]Ins(1,3,4,5)P4 as substrate. Both Ins(1,3,4,5,6)P5 and InsP6 were very potent inhibitors of the Ins(1,3,4,5)P4 3-phosphatase. The Ki values were approximately 60 nM and approximately 3 nM for Ins(1,3,4,5,6)P5 and InsP6 respectively. Ins(1,3,4,5,6)P5 and InsP6 also inhibited the Ins(1,4,5)P3/Ins(1,3,4,5)P4 5-phosphatase. Using Ins(1,3,4,5)P4 as substrate, the Ki values were about 35 microM and 15 microM for Ins(1,3,4,5,6)P5 and InsP6 respectively. The concentrations which led to a 50% inhibition of Ins(1,4,5)P3 (0.5 microM) degradation by the 5-phosphatase were about 20 and 10 microM for the pentakis- and hexakis-phosphate respectively. As the intracellular concentrations of Ins(1,3,4,5,6)P5 and InsP6 are high (up to 60 microM) compared with those of the inositol trisphosphates and tetrakisphosphates, it is possible that the highly phosphorylated inositol phosphates act as regulators in the metabolism of Ca(2+)-mobilizing inositol phosphates.
以[5-32P]Ins(1,3,4,5)P4为底物，检测了高度磷酸化的肌醇磷酸对从猪脑可溶性部分富集的Ins(1,3,4,5)P4 3-磷酸酶的影响。Ins(1,3,4,5,6)P5和InsP6都是Ins(1,3,4,5)P4 3-磷酸酶的强效抑制剂。Ins(1,3,4,5,6)P5和InsP6的Ki值分别约为60 nM和约3 nM。Ins(1,3,4,5,6)P5和InsP6也抑制Ins(1,4,5)P3/Ins(1,3,4,5)P4 5-磷酸酶。以Ins(1,3,4,5)P4为底物时，Ins(1,3,4,5,6)P5和InsP6的Ki值分别约为35 μM和15 μM。导致5-磷酸酶对Ins(1,4,5)P3（0.5 μM）降解产生50%抑制的浓度，五磷酸酯和六磷酸酯分别约为20 μM和10 μM。由于与肌醇三磷酸和四磷酸相比，Ins(1,3,4,5,6)P5和InsP6的细胞内浓度较高（高达60 μM），因此高度磷酸化的肌醇磷酸有可能作为动员Ca(2+)的肌醇磷酸代谢的调节剂。
