Phosphatidyl inositol phosphates

C.1.3 Greys Method for Phosphatidyl inositol Phosphate Extraction... 

Fig. 6.9. A) Metabolism of phosphatidyl inositol lipids. The figure shows different membrane-associated phosphatidyl inositol phosphate compounds and their mutual conversion. PI3-kinase (PI3K) is responsible, in particular, for the formation of PtdIns(3,4,5)P3 from PtdIns(3,4)P2. For the reactions marked with a question mark, involvement of PI(3) kinase is not certain.

Fig. 8.9. Crosslinking of signal proteins with the help of protein modnles. A hypothetical protein is shown which contains SH2, SH3, PTB and PH domains. Recognition of phosphotyrosine residues occurs with the help of SH2 or PTB domains SH3 domains bind to proline-rich sequences (Pro in Protein 3) whilst the pleckstrin homology domains (PH domains) mediate binding to phosphatidyl-inositol-phosphates (PtdInsP) in the membrane. In an idealized scheme, the modular protein can associate several proteins (Protein 1 - Protein 3) and mediate interactions between these proteins (shown as broken arrows). The PH domain helps to recruit the complex to the cell membrane favoring interactions with other membrane-associated proteins (Protein X).

In addition to these well-characterized routes, further transformations of inositol phosphates and phosphatidyl-inositol phosphates are known which lead to the formation of nearly 30 inositol-containing compounds with potential messenger function. These reactions include phosphorylation to inositol polyphosphates as well as specific dephosphorylation by inositol phosphatases. However, for only some of these compounds the biochemical attack points are known and specific in vivo functions could be demonstrated (review Irvine and Schell, 2001). 

Lithium decreases production of adenosine 3c,5c-cyclic monophosphate (cAMP), and inhibits the recycling of phosphatidyl inositol phosphate to inositol, resulting in a decrease in inositol triphosphate (IP3). Lithium also affects the permeability of membranes to sodium and potassium. 

Phosphatidyl-inositol phosphate and P1P2 showed significant increases in carbofuran-trcaied hepatocytes in comparison to DMSO-treated control. Equimolar amounts of carbofuran or BNF used in the separate culture. significantly increased the hepatocyte membrane PKC activity compared to the control. Use of staurosporinc, a known inhibitor of PKC, counteracted the carbofuran- or BNF-induced increase in PKC activity. Interestingly, phorbol ester demonstrated an attenuation of the carbofuran- or BNF-induced increase in PKC activity, but it remained higher than the control value. 

Krauss, M., Kinuta, M., Wenk, M. R., De Camilli, P., Takei, K., and Haucke, V. (2003). ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidyl-inositol phosphate kinase type Igamma. J. Cell. Biol. 162, 113-124. 

Phosphatidyl inositol (phosphate group esterihed with inositol, PI) ... 

A. Inositol Phosphates.—Phosphatidyl inositol (71) is hydrolysed in mammalian tissues to wyo-inositol 1,2-cyclic phosphate (72).i myoinositol 1-phosphate (73) is released simultaneously but is not converted into (72) by the enzyme system. Periodate oxidation of (73) liberates orthophosphate quantitatively, the unstable dialdehyde phosphate (74) being an intermediate. Little or no orthophosphate is released from glucose 6-phosphate under the same oxidative conditions, and this reaction has been used to assay (73). 

The other activity associated with transmembrane receptors is phospholipase C. Phosphatidyl inositol is a membrane phospholipid that after phosphorylation on the head group is found in the membrane as a phos-photidylinostitol bis phosphate. Phospholipase C cleaves this into a membrane associated diacylglycerol (the lipid part) and inositol trisphosphate (IP3, the soluble part). Both play a later role in elevating the level of the second messenger, Ca2+. 

Figure 6.8. Cyclic and non-cyclic inositol phosphates. Hydrolysis of phosphatidyl 4,5-bisphosphate (PIP2) by phospholipase C can generate cyclic and non-cyclic inositol phosphates.

Figure 6.9. Pathways of inositol phosphate metabolism. Ins 1,4,5-P3, generated via the hydrolysis of phosphatidyl 4,5-bisphosphate by phospholipase C, can be metabolised by a kinase (to generate Ins 1,3,4,5-P4) or via a phosphatase (to yield Ins 1,4-P2). These products can be metabolised further to produce inositol, which itself may be sequentially phosphory-lated to regenerate phosphatidylinositol 4,5-bisphosphate.

Glycerophospholipids are used for membrane synthesis and for producing a hydrophilic surface layer on lipoproteins such as VLDL. In cell membranes, they also serve as a reservoir of second messengers such as diacylglycerol, inositol 1,4,5-triphosphate, and arachidonic acid. Their structure is similar to triglycerides, except that the last fatty acid is replaced by phosphate and a water-soluble group such as choline (phosphatidylcholine, lecithin) or inositol (phosphatidyl-inositol). 

Phospholipids containing phosphatidyl, inositol, lecithin, serine, and ethanolamine (Stevenson 1986) are the second most abundant identifiable form of organic P in the upper layer of the subsurface. These groups contain glycerol, fatty acids, and phosphate (Sims and Pierzjinski 2005). The P in the structure is a diester, which is more susceptible to degradation in soils than monoesters. 

The other phospholipids can be derived from phosphatidates (residue = phosphatidyl). Their phosphate residues are esterified with the hydroxyl group of an amino alcohol choline, ethanolamine, or serine) or with the cyclohexane derivative myo-inositol. Phosphatidylcholine is shown here as an example of this type of compound. When two phosphatidyl residues are linked with one glycerol, the result is cardiolipin (not shown), a phospholipid that is characteristic of the inner mitochondrial membrane. Lysophospholipids arise from phospholipids by enzymatic cleavage of an acyl residue. The hemolytic effect of bee and snake venoms is due in part to this reaction. 

Fig. 3.15. Typical strucutre of a glycosyl phosphatidyl inositol (GPI) anchor. Ins inositol GlcN 2 -amino, 2 -deoxy-glucose Man mannose Etn Ethanolamine, P phosphate.

---