Serine base-exchange

Buratta, S., Migliorati, G., Marchetti, C., Mambrini, R., Riccardi, C., and Mozzi, R., 2000, Dexamethasone increases the incorporation of [3H]serine into phosphatidylserine and the activity of serine base exchange enzyme in mouse thymocytes a possible relation between serine base exchange enzyme and apoptosis. MoZ. Cell. Biochem. 211 61-67. 

The primary pathway for synthesis of PS in mammalian tissues is provided by the base exchange reaction, in which the ethanolamins of PE is exchanged for free serine (see Figure 17.6). This reaction although reversible, is used primarily to produce the PS required for membrane synthesis. 

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. 

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

Biosynthesis of phosphatidylethanolamine from phosphatidylserine. The base-exchange enzyme on the cytosolic face of the endoplasmic reticulum can interconvert these phospholipids in the pre,sence of Ca and the alternate head group, serine or ethanolamine. The decarboxylase is localized in the inner membrane of mitochondria and catalyzes the nonequilibrium conversion of phosphatidylserine to phosphatidylethanolamine. 

Phosphatidylserine makes up 10% of phospholipids in mammals. This phospholipid is synthesized in a base-exchange reaction of serine with phosphatidylcholine or phosphatidylethanolamine. In the reaction, serine replaces choline or ethanolamine. 

In bacteria, phosphatidylethanolamine is formed by decarboxylation of phosphatidylserine (Fig. 11.15). This is in sharp contrast to animal (Bell and Coleman, 1982) and plant tissues (Moore, 1982). Furthermore, in bacteria serine is incorporated into phosphatidylserine via CDP-diacylglycerol (Lennarz, 1970) rather than by base exchange as in animals (Spanner, 1982). 

The incorporation of [ C]serine into phospholipids was catalyzed by a microsomal preparation from etiolated pea seedlings. This was apparently a base-exchange reaction (Vandor and Richardson, 1968) ... 

Fig. 3. Displacement of tritiated L-serine from rat brain microsomal labelled Ptd-Ser by the addition of P c labelled ethanolamine L-serine ( - - ) and choline ( A-A-A). The Ptd-Ser pre-labelling of membranes was carried out by base-exchange with 1.95 mM l3-% L-serine for 15 min. For other details, see Fig. 2.

Rather similar data are shown in Table 2, which refers to displacement experiments carried out on microsomal Ptd-Cho pre-label-led Xn )Xi/lo from CDP-choline through the Kennedy pathway. Indeed, after 9 min of incubation, L-serine and ethanolamine displace the lipid-choline moiety by only 6% and 4%, respectively, and choline by only 2%. These data differ essentially from those described in Fig. 2, which reported the percentages of displacement rates of lipid-choline pre-labelled by base-exchange, and which... 

Fig. 4. GABA uptake in synaptosomal fractions of rabbit brain, as a function of base-exchange reaction with increasing concentrations of L-serine. GABA uptake (% of T/M, see Sellestrbm Hamberger,...

When the synaptosomal Ptd-Ser, produced by base-exchange, was displaced by the three unlabelled bases (ethanolamine, L-serine or choline), as shown in Fig. 4, a general inhibitory effect on GABA uptake was produced, which was well evident when choline or ethanolamine were used as base-displacers. The homologous-type of base-displacement (i.e., L-serine with Ptd-Ser) produced only a light modification of the basic uptake (Fig. 4). 

Fig. 5. GABA uptake in synaptosomal fractions of rabbit brain, as a function of base-exchange reaction with increasing P c -ethanol-amine concentrations. Base-exchange with ethanolamine ( A- A-A) base-exchange with ethanolamine, followed by displacement of membrane Ptd-Etn by unlabelled ethanolamine ( A- A - A), L-serine ( - - ) or choline (o-o-o). See Fig. 4 for additional information.

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