Phosphatidylserine decarboxylation

Two routes to phospholipid biosynthesis are known in either, the participation of CTP is necessary. The first route involves phosphatidic acid in phosphoglyceride biosynthesis. Phosphatidic acid reacts with CTP to yield CDP-diglyceride which, as a coenzyme, can participate in the transfer of diglyceride onto serine (or inositol) to produce phosphatidylserine (or phosphatidylinositol). Serine phosphatides are liable to decarboxylation (pyridoxal phosphate acting... 

Figure 1. Control of mitochondrial biogenesis by the nuclear genome. Most mitochondrial proteins, including cytochrome c, are nuclear gene products which are subsequently imported into mitochondria. Similarly, most enzymes involved in synthesis of mitochondrial phosphoplipids are encoded in the nuclear genome. Being located in the endoplasmatic reticulum, they synthesize phosphatidylcholine (PtdCho), phosphatidylserine (PtdSer), phosphatidylglycerol (PG) and phosphatidylinositol (Ptdins). The phospholipids are transferred to the outer membrane. The imported lipids then move into the inner membrane at contact sites. Mitochondria then diversify phospholipids. They decarboxylate phosphatidylserine to phosphatidylethanolamine (PtdEtN), but the main reaction is the conversion of imported phosphatidylglycerol to cardiolipin (CL). Cardiolipins localize mainly in the outer leaflet of the inner membrane.

Figure 1. Synthetic pathway for PS and PE in mammalian cells. The major steps occuring in the synthesis and interconversion of PS and PE are shown. The PS synthases condense serine with a phosphatidyl moiety derived from PC and PE. The nascent PS can be converted to PE by decarboxylation. PE can also be formed by transfer of a phosphoethanolamine moiety from CDP-ethanolamine to diacylglycerol via the Kennedy pathway. The abbreviations used are PC, phosphatidylcholine PS, phosphatidylserine PE, phosphatidylethanolamine DG, diacylglycerol PSD, phosphatidylserine decarboxylase PSS, PS synthase.

Borkenhangen, J.D., Kennedy, E.P., and Fielding, L., 1961, Enzymatic formation and decarboxylation of phosphatidylserine. J. Biol. Chem., 236 PC28-29. 

Shiao, Y.J., Lupo, G., and Vance, J.E., 1995, Evidence that phosphatidylserine is imported into mitochondria via a mitochondria-associated membrane and that the majority of mitochondrial phosphatidylethanolamine is derived from decarboxylation of phosphatidylserine./. Bio/. Chem. 270 11190-11198. 

Another pathway to make PE, which allows cells to grow in the absence of ethanolamine, is the decarboxylation of phosphatidylserine (PS) by PS decarboxylase (VoeUcer, 1997). 

Transfer of a phosphocholine residue to the free OH group gives rise to phosphatidylcholine (lecithin enzyme l-alkyl-2-acetyl-glycerolcholine phosphotransferase 2.7.8.16). The phosphocholine residue is derived from the precursor CDP-choline (see p. 110). Phos-phatidylethanolamine is similarly formed from CDP-ethanolamine and DAG. By contrast, phosphatidylserine is derived from phosphatidylethanolamine by an exchange of the amino alcohol. Further reactions serve to interconvert the phospholipids—e.g., phosphatidylserine can be converted into phosphatidylethanolamine by decarboxylation, and the latter can then be converted into phosphatidylcholine by methylation with S-adenosyl methionine (not shown see also p. 409). The biosynthesis of phosphatidylino-sitol starts from phosphatidate rather than DAG. 

Phosphatidylserine and phosphatidylglycerol can serve as precursors of other membrane lipids in bacteria (Fig. 21-25). Decarboxylation of the serine moiety in phosphatidylserine, catalyzed by phosphatidylserine decarboxylase, yields phosphatidylethanolamine. In E. coli, condensation of two molecules of phosphatidylglycerol, with elimination of one glycerol, yields... 

In bacteria, phosphatidylserine is formed by the condensation of serine with CDP-diacylglycerol decarboxylation of phosphatidylserine produces phosphatidylethanolamine. Phosphatidylglycerol is formed by condensation of CDP-diacylglycerol with glycerol 3-phosphate, followed by removal of the phosphate in monoester linkage. 

Phosphatidylinositol (Ptdlns) 563, 565, 566s in signalling 563 - 566 Phosphatidylinositol 3-kinase 565 Phosphatidylinositol 4,5-bisphosphate 563 Phosphatidylserine 383s, 564 decarboxylation of 753 Phosphatidylserine decarboxylase 409, 755 3 -Phosphoadenosine 5 -phosphosulfate (PAPS) 659 Phosphoadenylation... 

The formation of phosphatidylserine and possibly other phospholipids in animal tissues may also be accomplished by exchange reactions (Eq. 21-10, step a). 82 83 At the same time, decarboxylation of phosphatidylserine back to phosphatidylethanolamine (Eq. 21-10, step b) also takes place, the net effect being a catalytic cycle for decarboxylation of serine to ethano-lamine. The latter can react with CTP to initiate synthesis of new phospholipid molecules or can be converted to phosphatidylcholine (step c). However, unless there is an excess of methionine and folate in the diet, choline is an essential human nutrient.184... 

In prokaryotes, phosphatidylserine is made from CDP-diacylglycerol (see fig. 19.3). The enzyme for this reaction is absent in animal cells, which rely on a base exchange reaction in which serine and ethanolamine are interchanged (fig. 19.8). Although the reaction is reversible, it usually proceeds in the direction of phosphatidylserine synthesis. Phosphatidylserine can be converted back to phos-phatidylethanolamine by a decarboxylation reaction in the mitochondria. This may be the preferred route for phosphatidylethanolamine biosynthesis in some animal cells. Furthermore these two reactions (see fig. 19.8) establish a cycle that has the net effect of converting serine into ethanolamine. This is the main route for ethanolamine synthesis... 

Phosphatidylserine biosynthesis in animals is catalyzed by a base exchange enzyme on the endoplasmic reticulum. Decarboxylation of phosphatidylserine occurs in mitochondria. The cyclic process of phosphatidylserine formation from phosphatidylethanolamine and the reformation of phosphatidylethanolamine by decarboxylation has the net effect of converting serine to ethanolamine. This is a major mechanism for the synthesis of ethanolamine in many eukaryotes. 

Phosphatidylcholine is synthesized via the Kennedy pathway (Kennedy and Weiss, 1956) in three consecutive steps catalyzed by the enzymes choline kinase, phosphocholine cytidyltransferase, and phosphocholine transferase. Phospha-tidylethanolamine is synthesized via the corresponding pathway for ethanolamine or by decarboxylation of phosphatidylserine (Borkenhagen et al., 1961) or by base exchange (Bjerve, 1973). In immobilized breast cancer cells, flux in these pathways... 

Bjerve, K.S. (1973). The Ca2+-dependent biosynthesis of lecithin, phosphatidylethanolamine and phosphatidylserine in rat liver subcellular particles. Biochim. Biophys. Acta 296,549-562. Bloch, F., Hansen, W.W., Packard, M. (1946). Nuclear induction. Phys. Rev. 69,127. Borkenhagen, L.F., Kennedy, E.P., Fielding, L. (1961). Enzymatic formation and decarboxylation of phosphatidylserine. J. Biol. Chem. 236, PC28-PC30. 

Another reaction shown in Figure 19.16 is the formation of phosphatidylserine from phosphatidylethanolamine. This reaction also serves to make more phosphatidylethanolamine by decarboxylating the phosphatidylserine. The net reaction is thus... 

Phosphatidylserine arises by an exchange of the ethanolamine residue of phosphatidylethanolamine for a seryl group. Decarboxylation of the serine of phosphatidylserine reforms phosphatidylethanolamine. Three successive methylation reactions convert phosphatidylethanolamine to phosphatidylcholine. 5-Adenosyl-methionine is the methyl-group donor (Chap. 15) (see Fig. 13-14). 

Pyridoxal phosphate has a clear role in lipid metabolism as the coenzyme for the decarboxylation of phosphatidylserine, leading to the formation of phosphatidylethanolamine, and then phosphatidylcholine (Section 14.2.1), and membrane lipids from vitamin Bg-deficient animals are low in phosphatidylcholine (She et al., 1995). It also has a role, less well defined, in the metabolism of polyunsaturated fatty acids vitamin Bg deficiency results in reduced activity of A desaturase and impairs the synthesis of eicosapentanoic and docosahexanoic acids (Tsuge et al., 2000). 

Phosphatidylcholine can be synthesized by the pathway shown in Figure 14.3. Decarboxylation of phosphatidylserine to phosphatidylethanolamine (cephalin) is followed by methylation in which S-adenosylmethionine is the methyl donor to yield successively the relatively rare mono- and dimethyl derivatives, then phosphatidylcholine. 

FIGURE 6,6 rhosphattdjflcholine (PC) synthesis by phosphatidylserine (PS) decarboxylation and base exchange. Serine serves as the source of the carbon skeleton of choline,... 

FIGURE 6.5 Phosphatidylethanolamine (PE) synthesis by decarboxylation of phosphatidylserine (PS). Wamin Bg is required for catal)rtic activity. 

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. 

Phosphatidylethanolamines can also be synthesized by decarboxylation of phosphatidylserine and in mammals principally through action of the Ca -mediated base exchange enzyme (Figure 19-3). Phosphatidylserine production in liver occurs at the cytosolic face of the endoplasmic reticulum. In brain tissue, this phospholipid accounts for up to 15% of the total phospholipid content. 

Phosphatidylserine is generated in a reaction in which the ethanolamine residue of phosphatidylethanolamine is exchanged for serine (Figure 12.19). This reaction, which is catalyzed by an ER enzyme, is reversible. In mitochondria, phosphatidylserine is converted to phosphatidylethanolamine in a decarboxylation reaction. 

Phosphatidylserine can be synthesized from phosphatidylethanolamine in a reaction in which the polar head groups are exchanged. Phosphatidylethanolamine can also be synthesized from phosphatidylserine in a decarboxylation reaction. This reaction is an important source of ethanolamine in many eukaryotes. 

Elabbadi, N., Ancelin, M. L., and Vial, H. J. (1997). Phospholipid metabolism of serine in Plasmodium-infected erythrocytes involves phosphatidylserine and direct serine decarboxylation. Biochem. ]. 324(Pt 2), 435M45. 

As already noted, the final steps In the synthesis of cholesterol and phospholipids take place primarily In the ER, although some of these membrane lipids are produced In mitochondria and peroxisomes (plasmalogens). Thus the plasma membrane and the membranes bounding other organelles (e.g., Golgi, lysosomes) must obtain these lipids by means of one or more Intracellular transport processes. For example. In one Important pathway, phosphatidylserine made In the ER Is transported to the Inner mitochondrial membrane where It Is decarboxylated to phosphatidylethanolamlne, some of which either returns to the ER for conversion Into phosphatidylcholine or moves to other organelles. 

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