Portela Torres, Paloma; (2020) Inositol phosphate pathway evolution and synthesis in Dictyostelium discoideum. Masters thesis (M.Phil), UCL (University College London).

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Abstract

Inositol phosphates (InsPs) are polar water-soluble derivatives of the six- carbon cyclitol inositol. They are synthesized, through phosphorylation reactions, by kinases of four distinct families: IPK, IP5-2K, ITPK1 and PPIP5K, which are thought to be present across all eukaryotes. A pleiotropy of functions has been ascribed to InsPs, from nutrient storage as phytate (InsP6) in plant seeds to the regulation of energy metabolism for the highly phosphorylated inositol pyrophosphates (PP-InsPs). PP-InsPs were first identified and structurally described in the slime mould D. discoideum, in part due to the high concentrations of these molecules in amoeba. However, the amoeba knockout strains for the homologous enzymes synthesising PP-InsPs in humans (and yeast), IP6K (kcs1) and PPIP5K (vip1), do not present clear phenotypes. The work presented in this thesis expanded our biochemical understanding of these kinases by identifying additional isomers of inositol pyrophosphates and IpkA as the main source of InsP8 in the social amoeba. These findings shed light into the evolution of the inositol phosphate pathway and suggested an increased complexity of isomers and enzymes. Inositol phosphate kinase functions were identified in all domains of the tree of life as well as certain viruses, increasing our understanding of the origin and diversification of the inositol phosphate pathway.

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