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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 40

Module 2: Figure phosphoinositide metabolism

4
PtdIns3P PtdIns3,5P 2 Inositol lipid
13 metabolism
1
11
6
2 7
PtdIns PtdIns4P 5 PtdIns3,4P 2 PtdIns3,4,5P 3
8
3 12 8
9 10
PtdIns5P 6 PtdIns4,5P 2

11
PtdIns3,5P 2
Phospholipase C
Lipid resynthesis

DAG Ins1,4,5P 3
G-6-P

Inositol phosphate
Inositol synthase Inositol metabolism

Summary of phosphoinositide metabolism.
The metabolism of phosphoinositides is separated into inositol lipid metabolism and inositol phosphate metabolism. In the former case, the parent
molecule phosphatidylinositol (PtdIns) (Module 2: Figure PtdIns structure) undergoes a series of phosphorylation reactions to create various poly-
phosphoinositides many of which have messenger functions. For example, PtdIns4,5P 2 functions both as a messenger and as a precursor for the
formation of other phosphoinositide lipid signalling molecules such as PtdIns3,4,5P 3 . In addition, it can be hydrolysed to form the second messengers
inositol 1,4,5-trisphosphate (Ins1,4,5P 3 ) and diacylglycerol (DAG). The Ins1,4,5P 3 is the major input into a complex pathway of inositol phosphate
metabolism (Module 2: Figure inositol phosphate metabolism). One of the outputs of this metabolism is inositol that is used for the resynthesis of
PtdIns. Cells also have a 1-L-myo-inositol-1-phosphate synthase that can convert glucose 6-phosphate (G-6-P) into inositol.

Module 2: Figure PtdIns structure

Phosphatidylinositol (PtdIns)

C C
O O
C C C O P
H H H 2
2
O
OH 1 OH
OH OH
3 OH 5
4

Molecular structure of PtdIns.
The backbone of the molecule consists of a glycerol moiety. Two of the carbons carry fatty acids that insert into the hydrophobic domain of the
membrane, whereas the remaining carbon is attached to a phosphate group that is linked to an inositol ring that projects out into the cytosol. The
hydroxy groups on the 3-, 4- and 5-positions can be phosphorylated further (see Module 2: Figure phosphoinositide metabolism)

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