Figure 1. Pathways of enzymatic synthesis of PP-InsPs.

Figure modified from Shears 2009 [5]. The IP6Ks (myoinositol hexakisphosphate kinase; Kcs1 in yeast [48]), of which there are three isoforms in mammals, IP6K1, IP6K2 and IP6K3 [26,48,52], phosphorylate InsP₆ and 1-InsP₇ at the 5 position [41,53]. The PPIP5Ks (Vip1 in yeast [21]), of which there are two isoforms in mammals, PPIP5K1 and PPIP5K2 [18,19], phosphorylate InsP₆ and 5-InsP₇ at the 1 position [20,41]. Thus, the concerted actions of the IP6Ks and the PPIP5Ks leads to two routes of synthesis to InsP₈, which are designated pathway I and pathway II after Padmanabhan et al. [17]. The diphosphate groups that are added by these kinases are hydrolysed by a family of PP-InsP phosphohydrolases (DIPPs) [44,45].