Inositol synthetic pathway

Enzyme Ei is the phospholipase A, for which there is an excess of substrate in the plasma membrane i.e. a zero order process. (Eor details of this process, see Chapter 11). E, is a phosphatase, which catalyses a first order process. In fact, IP2 can be hydrolysed to produce IPi which is further hydrolysed to produce free inositol. The latter is salvaged by using it to re-form phosphatidylinositol in the phospholipid synthetic pathway and then phosphorylated to prodnce PIP2 (Chapter 11, Eigure 11.21). These reactions are not jnst of biochemical interest bnt are involved in the treatment of bipolar disease a mental disorder. 

Figure 2. Biosynthetic pathways from glucose 6-P to myo-inositol tetra/r/.vphosphates. The six carbons of the Ins ring are numbered according to the D-numbering convention. The pathways to the center-left proceed entirely via soluble myo-inositol (Ins) phosphates. Pathways to the center-right proceed via phosphatidylinositol (Ptdlns) phosphates. Questionmarks indicate synthetic steps that have not been confirmed in chemical, molecular or genetic analyzes. In addition, the hydrolysis of PtdIns(3,4,5)P3 to yield Ins(l,3,4,5)P4 has not been observed in any experiments, and is entirely speculative. P = PH204.

By comparison with alcohol asymmetric acylation (i.e., esterification) as discussed above, alcohol asymmetric phosphorylation has not attracted so much attention from the synthetic community thus far. This is rather curious given the pivotal importance of phosphorylated alcohols in biological systems where three of the most important and weU-studied signal transduction pathways, the mitogen-activated protein kinase pathway (MAPK), adenylyl cyclase dependent pathway (cAMP), and inositol triphosphate/diacylglycerol pathway (IP3/DAG), all rely critically on chemo- and/or stereoselective alcohol phosphorylation/dephosphorylation by kinase/phosphatase enzymes, respectively [76]. 

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