Cytidine diphosphate diacylglycerol

APBD adult polyglucosan body disease CDP-DAG cytidine diphosphate diacylglycerol... 

The type II pneumocytes synthesize phosphatidylcholine in a fashion quite different from that in other cells. Most other cells synthesize phosphatidylserine from cytidine diphosphate diacylglycerol and serine. The phosphatidylserine is then decarboxylated to yield phosphatidyl ethanoiamine. The final step is the successive donation of three methyl groups via S-adenosylmethionine to form phosphatidylcholine. The pulmonary biosynthetic pathway is shown in Figure 54-2. The enzyme choline phosphotransferase forms PC directly from cytidine diphosphocholine and diacylglycerol. Phosphatidylinositol formation peaks at about 35 weeks. As PI decreases in concentration, PG begins to increase. 

Complete hydrolysis of phosphatidyl choline yields phosphoric acid, glycerol, saturated and unsaturated fatty acids. Phosphatidyl choline and phosphatidyl ethanolamine are obtained by routes similar to the above (11.102). In eukaryotic cells, various phospholipids are biosynthesised from phosphatidic acid via cytidine diphosphate diacylglycerol (11.103). 

An alternative fatty acid was introduced into position 2 following phospholipase A hydrolysis, and final conversion to phosphatidylcholine or phosphatldylethanolamine was accomplished by direct amination. Cytidine diphosphate diacylglycerols are essential Intermediates in the biosynthesis of several... 

Figure 2. The so-called canonical phosphoinositide pathway . The continuous phosphorylation/dephosphorylation reactions allow a steady-state level of Ptdins, PtdIns(4)P and PtdIns(4,5)P2 in the plasma membrane (PM). Cleavage of PtdIns(4,5)P2 by phospholipase C (PLC) generates the two well-known second messengers, inositol 1,4,5-trisphosphate (Ins(l,4,5)P3) and diacylglycerol (DAG). Besides its role as a protein kinase C (PKC) activator, DAG can be phosphorylated to phosphatidic acid (PA). The resynthesis of Ptdins from inositol and PA occurs mainly in the endoplasmic reticulum (ER). PPi, inorganic phosphate. PA-Pase, phosphatidic acid phosphatase. PA-TP, phosphatidic acid transport protein. PtdIns-TP, phosphatidylinositol transport protein. CDP-DAG, cytidine diphosphate-diacylglycerol. CMP, CDP and CTP, cytidine mono-, di- and triphosphate, respectively.

For example, it is well known that cardiolipin (CL) species are synthesized from the condensation of PG with cytidine diphosphate-diacylglycerol (CDP-DAG) species, and these newly synthesized immature species are remodeled into mature CL species from available donor acyl chains (Figure 5.1). Thus, this synthe-sis/remodeling process can be simulated by using the determined profiles of PG, PC, PE, and acyl CoA in comparison to the determined ion profile of CL species [58, 59]. The biological parameters in these simulations can be modified to compare CL profiles obtained from lipidomics analysis. Through the simulation, the... 

Figure 5.1 Schematic iUuslTation of cardiolipin biosynthesis and remodeling pathways. Newly synthesized cardiolipin (CL) (immature or nascent CL) is formed by the condensation of phosphatidylglycerol (PG) and cytidine diphosphate-diacylglycerol (CDP-DAG) catalyzed by CL synthase. Immature CL is then deacylated to form monolysoCL and then reacylated using acyl chains from acyl CoA or Iransacylated from the sn-2 acyl chain of PC and PE species, leading to the formation of matured CL.

The enzyme responsible for the final step of de novo biosynthesis of phosphatidylinositol (PI) is an endoplasmic reticulum enzyme the cytidine diphosphate-diacylglycerol (CDP-DAG) my< -inositol transferase (EC 2.7.8.11), or briefly PI-synthase. This enzyme catalyses the formation of PI and cytidine monophosphate (CMP) from CDP-DAG and myo-inosiiol [1], In a previous work [2], we found that the PI-synthase displayed a strong selectivity among the endogenous CDP-DAG molecular species used as substrates, in the microsomes from several plant tissues 16 0/18 2 and 16 0/18.3-CDP-DAG were markedly more utilized than other molecular species. Here, we are interested in the Pl-synthase selectivity among CDP-DAG molecular species, both when the enzyme was left within microsomal membranes or when it was solubilized and pre-purified. As a continuation of our work upon the solubilization of the Pl-synthase [3], we used CHAPS to solubilize the microsomal membranes as previously described. 

Figure 21-3 Major pathways of synthesis of fatty acids and glycerolipids in the green plant Arabidopsis. The major site of fatty acid synthesis is chloroplasts. Most is exported to the cytosol as oleic acid (18 1). After conversion to its coenzyme A derivative it is converted to phosphatidic acid (PA), diacylglycerol (DAG), and the phospholipids phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). Desaturation also occurs, and some linoleic and linolenic acids are returned to the chloroplasts. See text also. From Sommerville and Browse.106 See also Figs. 21-4 and 21-5. Other abbreviations monogalactosyldiacylglycerol (MGD), digalactosyldiacylglycerol (DGD), sulfolipid (SL), glycerol 3-phosphate (G3P), lysophosphatidic acid (LPA), acyl carrier protein (ACP), cytidine diphosphate-DAG (CDP-DAG).

Fig. 2. Targeted lipidomics of 2-AG metabolism. Postulated pathways for 2-AG metabolism. Abbreviations PLC, phospholipase C DAG, diacylglycerol DGL, diacylglycerol lipase MGL, monoacylglycerol lipase PLA, phospholipase A AT, acyltransferase TAGL, triacylglycerol lipase PIP2, phosphatidylinositol bisphosphate ABHD-6/12 hydrolase lyso-PL, lysophospholipid lyso-PA, lysophosphatidic acid PA, phosphatidic add P, phosphatase COX, cydooxygen-ase LOX, lipoxygenase CYP450, cytochrome P450 CDP, cytidine diphosphate.

C-labelled phosphatidylserine from phosphatldic acid has been reported the latter was converted to cytidine diphosphate (CDP) diacylglycerol, by reaction with CMP-morpholidate as the dlcyclohexylcarboxamidium salt, and thence to phosphatidylserine by a reaction with L-[U- C]serine catalysed by the... 

Chloroform solutions of dioleoylphosphatidylcholine (DOPC), dioleoyl-phosphatidylethanolamine (DOPE), dioleoylphosphatidylserine (DOPS), dioleoylphosphatidic acid (DOPA), and phosphatidylinositol (PI) from soybean are purchased from Avanti Polar Lipids (Alabaster, AL). Phosphatidylinositol 4-phosphate (PI4P), phosphatidylinositol 4,5-biphosphate (PIP2), and cytidine 5 -diphosphate-diacylglycerol (CDP-DAG) are obtained from Sigma (St. Louis, MO). Cholesterol is purchased from Nacalai... 

Cytidine diphosphate 5 -l,2-diacylglycerol (periodate-oxidized) (19) Separation of membrane-bound enzymes involved in phosphatidylglycerol synthesis by affinity chromatography 152... 

FIGURE 9.8 CTP synthase. CTP synthase catalyzes the transfer of an amino group to UTP, gCTierating CTP. Glutamine serves as the donor of the amino nitrogen. Folate is not involved in the synthesis of CTP. Cytidine 5 -diphosphate (CDP) is distinguished in that it is used in lipid metabolism, where it takes the forms of CDP-choline, CDP-ethanolamine, and CDP-diacylglycerol. 

---