If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Fatty Acid and Lipid Biosynthesis → Phospholipid Biosynthesis|
|Biosynthesis → Secondary Metabolites Biosynthesis → Sugar Derivatives Biosynthesis → Cyclitols Biosynthesis|
Some taxa known to possess this pathway include : Saccharomyces cerevisiae
Expected Taxonomic Range: Eukaryota
The phosphorylated inositol compounds described in this superpathway can be divided into two major groups - the phospholipids phosphatidyl inositols, and the cyclitols inositol phosphates.
The most prominent stereomer of inositol in nature is myo-inositol. The inositol molecule has six hydroxyl groups, and each of these can be replaced by a single or double (pyro) phosphate group, resulting in a very large number of different forms of phosphorylated inositols.
myo-inositol can combine with a CDP-diacylglycerol to form the glycerophospholipid an L-1-phosphatidyl-inositol, which serves as a a minor component in the cytosolic side of eukaryotic cell membranes. The most common fatty acids of phosphatidyl-inositol are stearate in the SN1 position and arachidonate in the SN2 position. When the inositol within the phospholipid is phosphorylated, the resulting phosphatidylinositol phosphate is called a phosphoinositide. Phosphoinositides can be phosphorylated at any of the 3', 4', or 5' positions on the inositol headgroup, generating a set of seven unique stereoisomers that have specific biological functions (see 3-phosphoinositide biosynthesis).
The phosphoinositides are membrane-bound lipids that function as structural components of membranes, as well as regulators of many cellular processes in eukaryotes, including vesicle-mediated membrane trafficking, cell wall integrity, and actin cytoskeleton organization. Different forms of phosphoinositides are associated with different membranes.
Phosphatidylinositol 4-phosphate is the major form in the Golgi apparatus, where it plays a role in the vesicular trafficking of secretory proteins from the Golgi to the plasma membrane.
Phosphatidylinositol 4,5-bisphosphate is the major form found at the plasma membrane and is involved in the regulation of actin cytoskeleton organization, as well as cell wall integrity, and heat shock response pathways.
Phosphatidylinositol 3-phosphate is found predominantly at endosomal membranes and in multivesicular bodies (MVB), where it plays a role in endosomal and vacuolar membrane trafficking.
Phosphatidylinositol 3,5-bisphosphate is found on vacuolar membranes where it plays an important role in the MVB sorting pathway.
Phosphatidyl-1D-myo-inositol 3,4-bisphosphate is used in as a secondary messenger, involved in the regulation of cellular events including growth, differentiation, vesicular sorting, glucose transport and platelet aggregation [Zhang98c, Shearn01].
The phospholipid phosphatidylinositol 4,5-bisphosphate can be hydrolyzed by the phospholipase C enzymes to form the extremely important secondary messanger compound D-myo-inositol (1,4,5)-trisphosphate (see D-myo-inositol (1,4,5)-trisphosphate biosynthesis). In addition to its role as a second messenger, D-myo-inositol (1,4,5)-trisphosphate is the starting point of several complex pathways that produce many different forms of phosphorylated inositols.
D-myo-inositol (1,4,5)-trisphosphate can be phosphorylated, either in a direct route (see 1D-myo-inositol hexakisphosphate biosynthesis I (from Ins(1,4,5)P3)) or via D-myo-inositol (1,3,4)-trisphosphate (see 1D-myo-inositol hexakisphosphate biosynthesis II (mammalian)), to the fully phosphorylated form 1D-myo-inositol 1,2,3,4,5,6-hexakisphosphate, also known as phytate. One of the intermediates of this pathway, D-myo-inositol 1,3,4,5,6-pentakisphosphate, is used to synthesize two other important secondary messengers - D-myo-inositol (1,4,5,6)-tetrakisphosphate (see D-myo-inositol (1,4,5,6)-tetrakisphosphate biosynthesis) and D-myo-inositol (3,4,5,6)-tetrakisphosphate (see D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis).
Phosphorylation does not end at 1D-myo-inositol 1,2,3,4,5,6-hexakisphosphate - this molecule is phosphorylated further by modification of one or more of the phosphates to pyrophosphates (see inositol pyrophosphates biosynthesis).
Even though not part of this pathway, the timely degration of these compounds is also a crucial part of their metabolism. More about it is available in 3-phosphoinositide degradation.
Subpathways: inositol pyrophosphates biosynthesis , D-myo-inositol-5-phosphate metabolism , 3-phosphoinositide biosynthesis , D-myo-inositol (1,4,5,6)-tetrakisphosphate biosynthesis , D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis , 1D-myo-inositol hexakisphosphate biosynthesis II (mammalian)
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