Eukaryotes diacylglycerol

Eukaryotes Synthesize Glycerolipids from CDP-Diacylglycerol or Diacylglycerol... 

FIGURE 25.19 Diacylglycerol and CDP-diacylglycerol are the principal precursors of glycerolipids in eukaryotes. Phosphatidylethanolamine and phosphatidylcholine are formed by reaction of diacylglycerol with CDP-ethanolamine or CDP-choline, respectively. 

FIGURE 25.20 Triacylglycerols are formed primarily by the action of acyltransferases on mono- and diacylglycerol. Acyltransferase in E. coli is an integral membrane protein (83 kD) and can utilize either fatty acyl-CoAs or acylated acyl carrier proteins as substrates. It shows a particular preference for palmitoyl groups. Eukaryotic acyltransferases nse only fatty acyl-CoA molecnles as substrates. 

FIGURE 25.22 CDP-diacylglycerol is a precursor of phosphaddylinositol, phosphaddyl-glycerol, and cardiolipin in eukaryotes. 

Eukaryotes Synthesize Anionic Phospholipids from CDP-Diacylglycerol... 

In eukaryotes, phosphatidylglycerol, cardiolipin, and the phosphatidylinositols (all anionic phospholipids see Fig. 10-8) are synthesized by the same strategy used for phospholipid synthesis in bacteria. Phosphatidylglycerol is made exactly as in bacteria. Cardiolipin synthesis in eukaryotes differs slightly phosphatidylglycerol condenses with CDP-diacylglycerol (Fig. 21-26), not another molecule of phosphatidylglycerol as in E. coli (Fig. 21-25). 

Phosphatidylinositol is synthesized by condensation of CDP-diacylglycerol with inositol (Fig. 21-26). Specific phosphatidylinositol kinases then convert phosphatidylinositol to its phosphorylated derivatives (see Fig. 10-17). Phosphatidylinositol and its phosphorylated products in the plasma membrane play a central role in signal transduction in eukaryotes (see Figs 12-8, 12-19). 

Synthesis of most phospholipids starts from glycerol-3-phosphate, which is formed in one step from the central metabolic pathways, and acyl-CoA, which arises in one step from activation of a fatty acid. In two acylation steps the key compound phosphatidic acid is formed. This can be converted to many other lipid compounds as well as CDP-diacylglycerol, which is a key branchpoint intermediate that can be converted to other lipids. Distinct routes to phosphatidylethanolamine and phosphatidylcholine are found in prokaryotes and eukaryotes. The pathway found in eukaryotes starts with transport across the plasma membrane of ethanolamine and/or choline. The modified derivatives of these compounds are directly condensed with diacylglycerol to form the corresponding membrane lipids. Modification of the head-groups or tail-groups on preformed lipids is a common reaction. For example, the ethanolamine of the head-group in phosphatidylethanolamine can be replaced in one step by serine or modified in 3 steps to choline. 

Phosphatidylglycerol and diphosphatidylglycerol are also synthesized in the mitochondria of eukaryotes by a pathway similar to that in prokaryotes. The only difference is that diphosphatidylglycerol in eukaryotes is made by the reaction of CDP-diacylglycerol with phosphatidylglycerol rather than the condensation of two molecules of phosphatidylglycerol as occurs in E. coli. 

In the first phase of phospholipid synthesis from glyc-erol-3-phosphate to phosphatidic acid, the pathways in E. coli and eukaryotes are very similar (see fig. 19.2). The major difference is that one additional pathway exists for generation of phosphatidic acid from dihydroxyacetone phosphate, an intermediate in glycolysis. Once phosphatidic acid is made, it is rapidly converted to diacylglycerol or CDP-diacylglycerol (see fig. 19.2) both of which are intermediates for the biosynthesis of eukaryotic phospholipids. 

CDP-diacylglycerol is also a precursor of phosphati-dylinositol (fig. 19.6), a lipid that is unique to eukaryotes. Phosphatidylinositol accounts for approximately 5% of the lipids present in animal cell membranes (see table 17.3). Also present, at much lower concentrations, are phosphatidylinositol-4-phosphate and phosphatidylino-... 

Reaction that converts CDP-diacylglycerol to phosphatidylinositol in eukaryotic cells. 

Cytidine triphosphate Diacylglycerols and lipid head groups Bacteria, archaea and eukaryotes ... 

Stereochemically, the structures of the archaeol analogs of PG, PGP, PGP-Me and PGS are unusual in that both glycerol moieties have the opposite configuration to those in the corresponding diacylglycerol forms of PG and PGP found in eubacteria and eukaryotes [11] (see Fig. 3). 

The first step in the pathway is the synthesis of PI from CDP-diacylglycerol and myo-inositol by PgsA (Rv2612c) [275]. Myo-inositol is uncommon in prokaryotes, but inositol phosphates and inositol-containing phosphoglycans are important in eukaryotic signaling pathways. The mycobacterial enzymes responsible for myo-inositol biosynthesis have been characterized [276,277]. 

Subsequent phosphorylations catalyzed by specific kinases lead to the synthesis of pkosphatidylinositol 4,5-bisphosphate, the precursor of two intracellular messengers diacylglycerol and inositol l,4,S-trisphosphate (Section 14.2). If the alcohol is phosphatidylglycerol, the products are diphosphatidylglycerol (cardiolipin) and CMP. In eukaryotes, cardiolipin is located exclusively in inner mitochondrial membranes and plays an important role in the organization of the protein components of oxidative phosphorylation. 

The diacylglycerol backbone in eubacteria and eukaryotes is sn-3-glycerol esterified at positions 1 and 2 with long-chain fatty acids (Fig. 2). In archaebacteria (Fig. 3), the opposite isomer sn-1-glycerol forms the lipid backbone and the hydrophobic domain is composed of phytanyl (saturated isoprenyl) groups in ether linkage at positions 2 and 3 (an archaeol)... 

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