Abstract
Inorganic polyphosphate (polyP) is a ubiquitous polymer of tens to hundreds of orthophosphate residues linked by high-energy phosphoanhydride bonds. In prokaryotes and lower eukaryotes, both the presence of polyP and of the biosynthetic pathway that leads to its synthesis are well-documented. However, in mammals, polyP is more elusive. Firstly, the mammalian enzyme responsible for the synthesis of this linear biopolymer is unknown. Secondly, the low sensitivity and specificity of available polyP detection methods make it difficult to confidently ascertain polyP presence in mammalian cells, since in higher eukaryotes, polyP exists in lower amounts than in yeast or bacteria. Despite this, polyP has been given a remarkably large number of functions in mammals. In this review, we discuss some of the proposed functions of polyP in mammals, the limitations of the current detection methods and the urgent need to understand how this polymer is synthesized.
Highlights
Arthur Kornberg and Igor Kulaev spent a large part of their careers working on inorganic polyphosphate
The discovery of the human inorganic polyphosphate (polyP) synthase would validate these previous findings and dramatically accelerate polyP research. This may be a herculean task considering that to date, more than 70 years after Arthur Kornberg and Igor Kulaev, started working on polyP, no enzyme carrying the ability to synthesize polyP in mammals has been identified
In contrast with what was previously demonstrated [9], we recently reported that D. discoideum cells lacking DdPpk1 have no detectable polyP levels demonstrating that this is the sole enzyme responsible for polyP synthesis in social amoeba [10]
Summary
Arthur Kornberg and Igor Kulaev spent a large part of their careers working on inorganic polyphosphate ( polyP). A large number of publications have reported on the diverse effects of exogenously added synthetic polyP to cultured cells. There are proteins, like the NAD kinase, able to use polyP instead of ATP as phosphate donor [21].
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