皇家华人

New publication in Advances in Biological Regulation for Saiardi Lab

In their in聽Advances in Biological Regulation, the Saiardi Lab reveal an unforeseen complexity in the聽inositol pyrophosphate metabolism of the social amoeba聽Dictyostelium discoideum. In addition to聽the traditional IP6K and the PPIP5K enzymes, the amoeba possesses at least one additional protein responsible for inositol pyrophosphates synthesis. The authors聽believe that this novel metabolism is not an amoeba peculiarity, but聽a common feature present in other organisms too. Furthermore, their study uncouples the link between the IP6K and PPIP5K to inorganic polyphosphate (polyP) cellular levels, providing聽a different perspective to phosphate regulation by inositol pyrophosphates.

Article abstract:

Initial studies on the inositol phosphates metabolism were enabled by the social amoeba聽Dictyostelium discoideum.聽The abundant amount of inositol hexakisphosphate (IP6聽also known as Phytic acid) present in the amoeba allowed the discovery of the more polar inositol pyrophosphates, IP7聽and IP8, possessing one or two high energy phosphoanhydride bonds, respectively. Considering the contemporary growing interest in inositol pyrophosphates, it is surprising that in recent years聽D. discoideum, has contributed little to our understanding of their metabolism and function. This work fulfils this lacuna, by analysing the聽ip6k, ppip5k听补苍诲听ip6k-ppip5Kamoeba null strains using PAGE,聽13C-NMR and CE-MS analysis. Our study reveals an inositol pyrophosphate metabolism more complex than previously thought. The amoeba Ip6k synthesizes the 4/6-IP7聽in contrast to the 5-IP7聽isomer synthesized by the mammalian homologue. The amoeba Ppip5k synthesizes the same 1/3-IP7聽as the mammalian enzyme. In聽D. discoideum, the聽ip6k聽strain possesses residual amounts of IP7. The residual IP7聽is also present in the聽ip6k-ppip5K聽strain, while the聽ppip5ksingle mutant shows a decrease in both IP7聽and IP8聽levels. This phenotype is in contrast to the increase in IP7聽observable in the yeast聽vip1螖 strain. The presence of IP8聽in聽ppip5k聽and the presence of IP7聽in聽ip6k-ppip5K聽indicate the existence of an additional inositol pyrophosphate synthesizing enzyme. Additionally, we investigated the existence of a metabolic relationship between inositol pyrophosphate synthesis and inorganic polyphosphate (polyP) metabolism as observed in yeast. These studies reveal that contrary to the yeast, Ip6k and Ppip5k do not control polyP cellular level in amoeba.