Medical Research Council Cell Biology Unit, Laboratory for Molecular Cell Biology, Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
J Biol Chem. 2011 Sep 16;286(37):31966-74. doi: 10.1074/jbc.M111.266320. Epub 2011 Jul 20.
Inorganic polyphosphate (poly-P) consists of just a chain of phosphate groups linked by high energy bonds. It is found in every organism and is implicated in a wide variety of cellular processes (e.g. phosphate storage, blood coagulation, and pathogenicity). Its metabolism has been studied mainly in bacteria while remaining largely uncharacterized in eukaryotes. It has recently been suggested that poly-P metabolism is connected to that of highly phosphorylated inositol species (inositol pyrophosphates). Inositol pyrophosphates are molecules in which phosphate groups outnumber carbon atoms. Like poly-P they contain high energy bonds and play important roles in cell signaling. Here, we show that budding yeast mutants unable to produce inositol pyrophosphates have undetectable levels of poly-P. Our results suggest a prominent metabolic parallel between these two highly phosphorylated molecules. More importantly, we demonstrate that DDP1, encoding diadenosine and diphosphoinositol phosphohydrolase, possesses a robust poly-P endopolyphosphohydrolase activity. In addition, we prove that this is an evolutionarily conserved feature because mammalian Nudix hydrolase family members, the three Ddp1 homologues in human cells (DIPP1, DIPP2, and DIPP3), are also capable of degrading poly-P.
无机多聚磷酸盐（poly-P）由通过高能键连接的磷酸基团链组成。它存在于每个生物体中，并且与多种细胞过程有关（例如磷酸盐储存、血液凝固和致病性）。其代谢主要在细菌中进行研究，而在真核生物中则基本未被描述。最近有人提出，多聚磷酸盐代谢与高度磷酸化肌醇物质（肌醇焦磷酸盐）的代谢有关。肌醇焦磷酸盐是一种磷原子数多于碳原子数的分子。与多聚磷酸盐一样，它们含有高能键，在细胞信号转导中发挥重要作用。在这里，我们表明无法产生肌醇焦磷酸盐的芽殖酵母突变体中的 poly-P 水平无法检测到。我们的结果表明这两种高度磷酸化分子之间存在明显的代谢平行关系。更重要的是，我们证明编码二腺苷和二磷酸肌醇磷酸水解酶的 DDP1 具有强大的多聚磷酸内切多磷酸水解酶活性。此外，我们证明这是一种进化上保守的特征，因为哺乳动物 Nudix 水解酶家族成员，即人类细胞中的三个 Ddp1 同源物（DIPP1、DIPP2 和 DIPP3），也能够降解 poly-P。
