Diacylglycerol-3-phosphate

Likewise, phosphatidyl inositol is formed by the transfer of a diacylglycerol phosphate unit from CDP-diacylglycerol to inositol. Subsequent phosphorylations catalyzed by specific kinases lead to the synthesis of phosphatidyl inositol 4,5-bisphosphate, an important molecule in signal transduction. Recall that hormonal and sensory stimuli activate phospholipase C, an enzyme that hydrolyzes this phospholipid to form two intracellular messengers—diacylglycerol and inositol 1,4,5-trisphosphate (Section 15.2). 

The enzymes for phosphatidate synthesis, acyl CoA synthetase, glycerol 3-phosphate acyltransferase and monoacylglycerol acyltransferase, are on both the outer mitochondrial membrane and the endoplasmic reticulum membrane. Diacylglycerol acyltransferase is only on the endoplasmic reticulum it may use either diacylglycerol phosphate synthesized on the endoplasmic reticulum or that synthesized on the mitochondrion. Triacylglycerol synthesized on the endoplasmic reticulum membrane may then enter lipid droplets either in the cytosol or, in the liver and intestinal mucosa, the lumen of the endoplasmic reticulum for assembly into lipoproteins - chylomicrons in the intestinal mucosa (section 4.3.2.2) and very low-density lipoprotein in the liver (section 5.6.2). 

The Fraser-Reid group has disclosed the synthesis of the Plasmodium falciparum GPI (30, Scheme 12.4) based on the use of n-pentenyl orthoester building blocks [30, 31, 64], In addition to the conserved pseudopentasaccharide, the target GPI features a myristoyl ester at the C2 position of the inositol, diacylglycerol phosphate at the Cl of inositol, and the mandatory phosphoethanolamine at Manlll. 

Hydrolysis of the phosphate ester function of the phosphatidic acid gives a diacylglycerol which then reacts with a third acyl coenzyme A molecule to produce a triacylglycerol... 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

In l,2-diacylglycerol-3-phosphate the phosphate group was esterified with choline by means of CDI to give the phosphatidyl choline ... 

Figure 4 Schematic representation of the Ca2+-transporting systems affecting cellular calcium homeostasis during hormonal stimulation, oq = oq-adrenergic receptor VP = vasopressin receptor PLC = phospholipase C PI = phosphatidylinositol PIP = phospha-tidylinositol-4-phosphate PIP2 = phosphatidylinositol-4,5-biphosphate IP3 = inositol-1,4,5-triphosphate DG = diacylglycerol PKC = protein kinase C. (Modified from Refs. 125 and 285.)...

Diacylglycerol kinase (DGK) from E. coli is a small 121 amino-acid, integral membrane protein which catalyses the conversion of diacylglycerol and MgATP to phosphatic acid and MgADP. DGK is homotrimeric,... 

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+. 

Metabotropic receptors, in contrast, create their effects by activating an intracellular G protein. The metabotropic receptors are monomers with seven transmembrane domains. The activated G protein, in turn, may activate an ion channel from an intracellular site. Alternately, G proteins work by activation or inhibition of enzymes that produce intracellular messengers. For example, activation of adenylate cyclase increases production of cyclic adenosine monophosphate (cAMP). Other effector mechanisms include activation of phospholipases, diacylglycerol, creation of inositol phosphates, and production of arachidonic acid products. Ultimately, these cascades can result in protein phosphorylation. 

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). 

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